A Report on Myeloma Patient Perspectives

Transcription

1 A Report on Myeloma Patient Perspectives A multi-stakeholder report and recommendations on the role of patients in myeloma research and treatment and the policy framework in which these take place. Summer 2013

2 Contents Foreword 4 Key recommendations 5 Executive summary 7 Methodology 10 Myeloma and patients needs 1. Setting the scene: About myeloma Best practices in the treatment and care of myeloma are they being achieved? Building a successful partnership with healthcare professionals Patients needs should be at the centre of research An effective policy framework for treatment and care in myeloma The power of patient advocacy in myeloma: making it happen 59 Achieving excellence in myeloma care case studies 69 Acknowledgements 71 About MPE 72 References 73 MPE Report on Myeloma Patient Perspectives 3

3 Foreword This report on Myeloma Patients Perspectives, developed by Myeloma Patients Europe in collaboration with a group of prominent European myeloma experts, deserves wide attention, not only from the myeloma community. It deserves attention from anyone who recognises the fundamental change that is occurring in our healthcare systems and their inevitable evolution towards patient-centred care and decision-making. The report explores patient perspectives on current approaches to myeloma treatment and care across Europe and their role in future research. It raises questions about how far current options meet patients needs and what the barriers and challenges are that limit access to the best possible treatment and care. It makes recommendations in five critical areas on what can be done to improve access, better involve patients in research and meet their needs more effectively. Most importantly, this report sets out key recommendations for patient involvement in decisions that affect them directly. It calls for ensuring that patients are equal partners in research and are given a formal role in the creation of policy that affects them. In fact, it goes one step further, to show the need for new models of collaboration between the patient community, governments, regulators, health technology assessment bodies, healthcare professionals, academia and the pharmaceutical industry to drive improved outcomes in myeloma. In the last 10 years the survival rates for this rare bone marrow cancer have approximately doubled. Yet, when patients are given a diagnosis of myeloma, they face an unknown number of years of treatment, remission, relapse and uncertainty as their cancer progresses. Many of them are diagnosed late and/or still do not have access to the best available treatment and the highest standards of care. This report represents the voice of myeloma patients in Europe and a broad consensus on what the priorities in myeloma should be to change the status quo. It is a much-needed roadmap for myeloma patient advocacy in Europe. For its readers, whether coming from government, health service, research or industry, this report should become a reference which cannot be ignored in any discussions that concern myeloma today and in the future. Dr Faith Davies member of the Faculty at the Institute of Cancer Research (ICR), London and Consultant Haematologist at The Royal Marsden, London. 4 MPE Report on Myeloma Patient Perspectives

4 Key recommendations Myeloma Patients Europe and all those who endorse the recommendations in this report should put in place plans of action with national governments, healthcare professionals, researchers, academia and pharmaceutical industry in order to address the five areas critical to achieving better outcomes for myeloma patients across Europe: 1) Define best practice in the treatment and care of myeloma Work to develop uniform European guidelines for the treatment of myeloma and defining best practice standards for holistic care including medical and psychological support Raise awareness of the symptoms of myeloma among general practitioners (GPs) and orthopaedic specialists to drive earlier referral and diagnosis Increase knowledge and capacity of haematologists and other members of the multidisciplinary team to help patients develop strategies for coping with the complications, side-effects of treatments and psychological impact of myeloma 2) Build a successful partnership with healthcare professionals Encourage patients to develop the knowledge and confidence to work in partnership with their doctors in deciding on treatment and to challenge recommendations and seek second opinions Support improvements in doctors training to include better communication skills and attention to the emotional as well as the physical needs of patients 3) Put patients needs at the centre of research Prioritise clinical trials that are more likely to result in improvements in patient outcomes in the clinic Support and invest in collaborative research e.g. through joint projects, EU-funded research consortia and undertakings such as the EU s Innovative Medicines Initiative Make use of the insight of patients in the concept, design and endpoints of clinical trials as well as the adoption and diffusion of research results 4) Ensure an effective policy framework for treatment and care in myeloma Develop national myeloma plans (at least within national cancer plans or national rare disease plans) and within them, clear objectives for diagnosis, treatment and management of myeloma Establish national Centres of Expertise and European Reference networks to ensure provision of access to high quality specialist care for all myeloma patients Examine European and national criteria for pricing and reimbursement of new treatments and to influence this where required to ensure that access is not restricted or prevented on the basis of cost 5) Utilise the power of patient advocacy Identify, inform and collaborate with key opinion leaders who can influence and make a difference to the services available to myeloma patients Encourage and train individual patients who have the skills to become expert patient advocates and actively contribute in committees responsible for clinical guidelines, clinical trial design, reimbursement and health policy decisions MPE Report on Myeloma Patient Perspectives 5

5 The recommendations made in this report are endorsed by: Amen Israeli Myeloma Patient Foundation (Amen) Arbeitsgemeinschaft Plasmozytom/Multples Myelom (APMM) Asociación Española de Afectados por Linfoma, Mieloma y Leucemia (AEAL) Associação Portuguesa Leucemias e Linfomas (APLL) Association of myeloma patients of Serbia (AMPS) Cancer and Stemcell Organization -Coordination Association (KOKDER) Contactgroep Myeloom en Waldenström Patiënten (CMWP) Contactgroep Myeloom en Waldenström Patiënten Vlaanderen vzw (CMP vzw) Društvo bolnikov z limfomom (DBL) Ege Uni tıp fak Suomen syöpäpotilaat-myelooma potilasverkosto Foundation for the Advancement of Bone Marrow Transplantation Switzerland (SFK) Leukaemiehilfe RHEIN-MAIN e.v. (LHRM) Multiples Myelom Selbsthilfe Oesterreich (MMSOe) Myelom Kontaktgruppe Schweiz (MKgS) Myeloma Euronet Romania (MER) Myeloma UK (MUK) MyMu Wallonie-Bruxelles (MyMu) Slovak Myeloma Society (SMyS-KP) Slovensko Združenje Bolnikov Z Limfomom In Levkemijo L&L Society for Assistance to Patients with Oncohaematological Diseases Udruga Za Podršku Oboljelima Od Multiplog Mijeloma (Mijelom CRO) Centro de Histocompatibilidade do Norte (CHN) Klub pacientů mnohočetný myelom (KPMM) 6 MPE Report on Myeloma Patient Perspectives

6 Executive summary This report has been developed to bring together the many complex issues faced by myeloma patients. Each chapter builds arguments which support the key recommendations to inform an agenda for myeloma patient groups and bring about the change required in their countries as well as across Europe towards improving outcomes in myeloma. The challenge of myeloma Myeloma is a rare type of cancer arising from plasma cells which are found in the bone marrow. It is believed by the Orphanet Europe-wide expert consortium to affect less than two people in every 10,000 1 ; but this may be a significant underestimate due to variation in data collection methods. Its treatment has advanced greatly in the last five years, but the most up-to-date treatments are not available across all of Europe. Myeloma patients suffer bone pain, anaemia and fatigue, plus increased risk from infection, as well as immense emotional challenges. Within a relatively short timeframe, many decisions will be needed about which treatment option to pursue. Some may want the most aggressive treatment to beat their myeloma, and others will prefer less aggressive treatment that has the potential to provide a better quality of life. Therefore it is vital that the healthcare afforded to myeloma patients addresses and meets these very individual needs. The patient s journey through myeloma meets repeated challenges: Rapid diagnosis is essential but rarely happens, because GPs so rarely encounter patients with myeloma. Many patients wait up to two years for a correct diagnosis Typical progression develops through several cycles of treatment, periods of remission and relapse: with continual uncertainty and anxiety Universal access to the most up-to-date treatments would be ideal, but evidence suggests that particularly in Eastern Europe, new medications are not available because of national reimbursement restrictions. This can even prevent access to medicines that have been approved by the European Medicines Agency (EMA), which should therefore be authorised in all EU member states. In non-eu countries, patients cannot even benefit from the EU legislation that provides reimbursement when accessing healthcare in another EU member state Many patients, again particularly in Eastern Europe, have no chance of participating in the clinical trials that could offer them improved treatment or reduced side-effects A good quality of life the aim for most patients depends on optimal pain relief, fatigue management, and treatments offering longer remissions Many treatments involve significant unpleasant side-effects, contributing to a greatly reduced quality of life and often cause patients to give up their treatment before achieving optimal results. Resistance also develops in myeloma cells. Both factors mean that new options are needed Psychological and emotional support is needed as a structured component of care, but across Europe, patients report that it is not available. This is especially important when myeloma returns even though it has responded to a prior treatment (relapse) or where myeloma has failed to respond to previous or current treatment (refractory myeloma) Palliative care is an important part of treatment and care and should be available from diagnosis and not just be considered in the last days of life Towards the last days of life, the needs of patients for effective pain relief and of patients, their families and carers for sensitive emotional support, are at their peak MPE Report on Myeloma Patient Perspectives 7

7 Significant barriers to better treatment and care As well as the problems already mentioned, economic constraints, regional differences and the lack of a uniform diagnosis and treatment pathway prevent access to optimal treatment and care. An important barrier is the inadequate transposition of relevant EU legislation; for example variation in implementation of the EU directive on cross-border healthcare may disadvantage patients with less economic resources. Effective communication between patient and doctor is vital, agreeing realistic, short-term goals that are constantly reassessed, and taking the emotional stresses into account. The patient s first need is for information, but it must be appropriate and offered at the right time for the individual. However, communication skills have rarely been taught in traditional medical training, so doctors ability varies considerably and would benefit significantly from greater uptake of continuing medical education in all countries. Ideally, training on communication skills should be added to the curricula of undergraduate medical schools. For their part, patients need to become more empowered; to develop the confidence and knowledge to seek a second opinion or to be referred to a specialist treatment centre. Myeloma is so rarely seen in primary care that it is important that patients take hold of all available information and the support of patient organisations, so that they can take an active part in managing their own myeloma. More traditional cultures, in which patients tend to accept their doctors opinion without question, may contribute to lower levels of myeloma diagnosis in the newer EU member states. Patients role in research Patients need information about current clinical trials and the opportunity to participate in them as appropriate. Continuing research into myeloma is urgently needed, as patients are all working on a limited timeframe. As long-term survival is limited to a small number of usually younger patients and to minimise the impact of treatment side-effects, it is particularly important that the advances of myeloma research in recent years are rapidly translated into treatments. However, this research is still fragmented and in need of greater coordination, in order to reduce duplication and enable faster progress. A greater focus on patient needs would bring faster benefit, for example identifying alternatives to current treatments that cause the worst side-effects. At this time of economic restraint, patient organisations can help towards this ideal by identifying priorities and objectives and by making the case for adequate, prioritised funding for research studies in both the private and public sectors. They should also highlight to government agencies the most promising outcomes from clinical trials, so that findings on new treatments can rapidly be built into treatment guidelines, which are many and vary significantly throughout Europe. Patients and their representatives also have a valuable contribution to make to the ethical committees and the protocol developers for clinical trials and the procedures relating to product market authorisation. 8 MPE Report on Myeloma Patient Perspectives

8 Myeloma treatment and care plans in Europe Most European Union member states have national cancer plans and the EU has recommended national plans for orphan diseases (which include myeloma) by Member states have been urged to support national or regional centres of expertise and reference networks in order to improve universal access to diagnosis and high-quality healthcare to all patients with conditions requiring a particular concentration of resources or expertise. This objective has been reinforced by the EU directive on patients rights to cross-border healthcare. The EU also has recommended improved access to orphan drugs, including compassionate provision even before authorisation or reimbursement, and possible incentives to promote research into these drugs and rare diseases. Clinical guidelines for diagnosis, management and treatment of medical conditions are based on the best available evidence, but standards of care do vary in practice because of the rarity of the condition and differences between the various sets of guidelines. Development of uniform European treatment guidelines would enable myeloma patients to receive the same high level of care throughout Europe. Further policy objectives that could benefit myeloma patients are support for continuing medical education and reminders about myeloma, so that GPs do not miss the rare myeloma diagnoses; and wider opportunities for patients to participate in ethical and regulatory committees for trials and market authorisation. So the broad framework to improve access to better care in the European Union has been set. There is a great need and opportunity for patient organisations throughout Europe to raise the level of specific awareness of myeloma among policy-makers and healthcare professionals. The role of patient advocacy Patient organisations have already made a great contribution to supporting and informing myeloma patients and advocating for priority issues. The current constraints they face are the increasing patient expectations at the time of economic restrictions and awareness of the need for a volunteer workforce to provide professional services. There is a significant need to develop the knowledge and skills of staff and volunteers, including training in advocacy and development of more expert patient advocates. More strategic partnerships need to be built between patient organisations and other stakeholders involved in myeloma from scientific societies to government and industry. Myeloma Patients Europe will work with the support of its member organisations across Europe and other groups which endorse the recommendations set out in this report. Our objective is to provide the myeloma community with the educational resources needed in order to foster more effective advocacy and raise the potential contribution of patient perspectives in decisions concerning myeloma. MPE Report on Myeloma Patient Perspectives 9

9 Methodology The information in the report has been compiled from a review of the literature and the initiatives of regulatory authorities, medical professional bodies and patient organisations, coupled with a series of interviews with myeloma patients. The report does not provide a country-by-country comparison and has not involved a comprehensive survey of patient views. It is intended to be a starting point for future work for Myeloma Patients Europe and its members. The report has been prepared with input and consultation from an MPE Writing Group and wider Advisory Board made up of healthcare professionals of all disciplines, researchers, patients and patient advocates. Its conclusions are therefore fully informed and jointly owned. 10 MPE Report on Myeloma Patient Perspectives

10 1. Setting the scene: About myeloma MPE Report on Myeloma Patient Perspectives 11

11 Myeloma and patients needs 1. Setting the scene: About myeloma Myeloma a rare form of bone marrow cancer is little known among the public and a GP is likely to meet only one or two patients in their career. This first chapter examines the nature of this rare cancer, what causes it and how it is treated. Most importantly, it looks at the many complex physical and emotional effects that myeloma has on patients and what treatment, support and other initiatives would help them best to cope with this devastating cancer. Key points There is no cure for myeloma The goal of treatment is to halt progression, induce remissions and improve quality of life It is a very individual cancer and therefore complications and responses to treatment vary greatly from patient to patient, making myeloma difficult to treat Multidisciplinary teams are needed to manage myeloma effectively Diagnosis and treatment bring profound emotional challenges to patients Treatments have improved dramatically in the last five to 10 years; however myeloma outcomes are still relatively modest much more needs to be done The cost of treating myeloma has increased dramatically over the last 10 years and this is likely to continue What is myeloma? Myeloma, also known as multiple myeloma, is a type of bone marrow cancer arising from plasma cells,which are normally found in the bone marrow. Plasma cells form part of the immune system. Normal plasma cells produce antibodies (also called immunoglobulins) to help fight infection. In myeloma, the abnormal plasma cells release only one type of antibody, known as paraprotein or M-protein, which has no useful function. It is often through the measurement of this paraprotein that myeloma is diagnosed and monitored. Bone marrow is the spongy material found in the centre of larger bones in the body. As well as being home to plasma cells, the bone marrow is the centre of blood cell production (red blood cells, white blood cells and platelets). In myeloma, the DNA of a plasma cell is damaged causing it to become malignant or cancerous. These abnormal plasma cells are known as myeloma cells. Unlike many cancers, myeloma does not exist as a lump or tumour. Instead, the myeloma cells divide and expand within the bone marrow. Myeloma affects multiple places in the body where bone marrow is normally active in an adult, i.e. within the bones of the spine, skull, pelvis, the rib cage and the areas around the shoulders and hips. The extremities the hands, feet and lower arm/leg regions are usually not affected and the function of these critical areas is usually fully retained. 12 MPE Report on Myeloma Patient Perspectives

12 Most of the medical problems related to myeloma are caused by the build-up of myeloma cells in the bone marrow and the presence of the paraprotein in the blood or in the urine. Common problems are bone pain, bone fractures, tiredness (due to anaemia), frequent or recurrent infections (such as chest and bladder infections), kidney damage and hypercalcaemia (raised calcium level in the blood). Some people develop myeloma after having been diagnosed with a condition called MGUS (Monoclonal Gammopathy of Undetermined Significance). This term describes the condition of the raised abnormal protein seen in myeloma (the paraprotein), but where there are no other features of myeloma (less than 10% plasma cells in bone marrow and no evidence of myeloma bone disease). In MGUS the M-protein level is less than 30g/L. The risk of transition from MGUS to active myeloma is very low; only a 1% chance each year of follow-up. Even if the myeloma cells are at a higher level of 10 30% of the total bone marrow, and the M-protein level may be higher than 30g/L, the growth rate can be very slow and with no symptoms. This is normally referred to as smouldering myeloma. Both MGUS and smouldering myeloma can change very slowly over a period of years and do not require active treatment. It is very important to establish the correct diagnosis, distinguishing MGUS and smouldering myeloma from active or symptomatic myeloma, which does require treatment. A very small proportion of myeloma patients (1 4%) can progress to plasma cell leukaemia, which is characterised by high levels of plasma cells circulating in the blood 2 and shorter survival. Myeloma quick facts Myeloma is rare, representing about 1% of all cancers It affects over 84,000 people in Europe A type of bone marrow cancer, myeloma arises from plasma cells in the bone marrow Affects multiple places in the body where bone marrow is active More common in people of African origin Affects more men than women Most commonly affects people over 60 Often described as the unknown cancer, there is no proven cause Most common symptoms and side-effects are bone pain, bone fractures, tiredness, frequent or recurring infections, kidney damage and hypercalcaemia One quarter of patients diagnosed with myeloma will die within one year Myeloma will always relapse there is no cure MPE Report on Myeloma Patient Perspectives 13

13 What causes myeloma? The cause of myeloma is believed to be a combination of genetic and environmental factors. Although a large amount of research has investigated the potential causes of myeloma, nothing has been proven to date. The factors most commonly implicated in the onset of myeloma are thought to be: The ageing process: As myeloma is more common later in life, it is thought that susceptibility may increase and effective immune function reduce with age, or that myeloma may result from a lifelong accumulation of toxic insults or antigenic challenges Exposure to certain chemicals, radiation and a weakened immune system: It is likely that myeloma develops when a susceptible individual has been exposed to one or more of these potential causal or trigger factors Being overweight or obese may also increase the risk, although more research is needed 3 Genetics. There is a rare tendency for myeloma to occur in families, but the likelihood is very low and no tests are currently available for this. Even when myeloma occurs more than once within a family, it may be due to a common exposure to environmental factors How does myeloma impact patients? Myeloma is a complex cancer that impacts patients both physically and emotionally. This nonexhaustive list shows the most common types of physical and emotional impact. Physical: Fatigue. Usually caused by anaemia, fatigue results in reduced independence, reduced ability to work and financial difficulties Pain Fractures and breaks Mobility problems Infertility. This can be a problem for younger patients, particularly now that new treatments can often prolong lives for more than five years Risk of infection. The continuing need to reduce the risk of day-to-day infection, because of a weakened immune system, often causes problems with maintaining an active social life Emotional/Psychological: Anxiety and depression. A feeling of stigma, a sense of isolation and fear of eventual relapse all contribute to anxiety and depression Profound emotional impact. As well as being an incurable cancer, myeloma is very rare and described as an unknown cancer, further adding to the emotional burden Decreased libido. Some treatments have a negative impact on sexual health and libido, which are often overlooked between patient and doctor, but can contribute to depression Exclusion and loss of self-esteem: Friends can be lost if they are unable to understand the situation Hair loss from chemotherapy can heighten the feeling of exclusion Living with the knowledge of myeloma can also bring a sense of personal loss of time and opportunity These issues all contribute to a loss of self-esteem 14 MPE Report on Myeloma Patient Perspectives

14 Judy s story The impact of myeloma When Judy was diagnosed, she was 33, with two small children and a full-time job as a stockbroker. She was used to working very hard, but began to catch a lot of infections. Blood tests and a bone marrow biopsy revealed smouldering myeloma. She was monitored for five years and gave up her job when her doctors felt her rising paraprotein level and low haemoglobin were indicative of progression to active myeloma and would soon affect her quality of life. She required a stem cell transplant, which gave a good partial remission. Her paraprotein started creeping up after four years of remission from the transplant, but Judy had a suboptimal response to subsequent treatment. After a further year and a half she began to feel pain in her hip, which intensified over the coming months and an MRI showed significant bone involvement from the myeloma. A second successful transplant has allowed Judy to get on with her life to a large degree. Her immune system is the main problem; it was affected by myeloma and worsened after treatment, so she has to be extremely careful to avoid travelling by plane and going to busy places where she could be at risk of infection. Myeloma and dealing with the drugs has also meant a huge mental and emotional strain. It s like living on the edge of a cliff most of the time. Even if you are a glass half-full sort of person it can be quite wearing, not knowing when the next relapse will come, and whether the drugs will be available in your country. With some cancers, after five years you are considered to be cured; with myeloma it s the opposite; you know it s always going to relapse. Judy also describes feelings of guilt for the anxiety her illness has given her family. Judy feels she was lucky in how quickly her myeloma was diagnosed, but that also gave her a long period of uncertainty while her smouldering myeloma was not treated. She is glad she has had access to good information and support. However, she feels that few consultants have a full understanding of what treatments would be best for an individual patient; not always taking into account whether a patient is at high risk or low risk, or running out of treatment options. And every centre with a myeloma service, she feels, should be able to advise patients on what clinical trials are on offer. Judy Dewinter, Myeloma patient, UK It s like living on the edge of a cliff most of the time. Even if you are a glass half-full sort of person it can be quite wearing, not knowing when the next relapse will come, and whether the drugs will be available in your country. Judy MPE Report on Myeloma Patient Perspectives 15

15 Do many people get it? Myeloma is a relatively rare cancer: Myeloma is rare, representing about 1% of all cancers in white people 6 and 15% of blood cancers 7 It is the second most common blood cancer after non-hodgkin s lymphoma. Myeloma is more common in people of African origin and less in Asians 6,8 It affects more men than women and most commonly affects people aged over 60 In 2008 the European Union s 27 member states were estimated to have about 73,000 myeloma patients and the whole of Europe over 84, The exact number of myeloma patients may be understated, as numbers are only derived from numbers of patients surviving for five years. Just under 37,000 new patients were diagnosed in 2008 alone 9. In Europe as a whole, a higher proportion of the population has myeloma in Western European countries than in Eastern Europe. This finding may at least in part due to less effective diagnosis or different methods of data collection. Estimated 5-year prevalence per 100,000 people* Source: International Agency for Research on Cancer: Globocan * the annual number of new cases multiplied by the probability of survival for 5 years A rare disease is defined as one affecting not more than 5 per 10,000 people (European Community Action programme on rare diseases ); other world regions have slightly differing definitions Derived from the latest cumulative estimates of 5-year surviving patients, from Globocan 2008, International Agency for Research on Cancer. The data for the whole of Europe represents EU-27 plus Belarus, Croatia, Moldova, the Russian Federation, Ukraine, Iceland, Norway, Albania, Bosnia Herzegovina, Croatia, Macedonia, Montenegro, Serbia and Switzerland. 16 MPE Report on Myeloma Patient Perspectives

16 Some countries within the European Union either have more people with myeloma in relation to the size of their population, or are diagnosing them more effectively. The number of new cases diagnosed varies by well over three times between the 27 countries. Myeloma incidence in EU-27, 2008: New cases per 100,000 population Sources: International Agency for Research on Cancer: Globocan / UN World Population Prospects However, the best rates of survival after five years in those countries are more than 4.5 times as great as the lowest rates. Myeloma prevalence in EU-27, 2008: 5 year surviving patients per 100,000 population LUX IT F BE SE NL ES SLOVEN UK D FL SLOVAK LITH CY HL DK EST IRL PT AT CZ POL HUNG MT BULG LAT ROM IT LUX F BE D UK NL SE ES SLOVEN LITH FL SLOVAK DK IRL EST AT CZ HL PT CY POL HUNG BULG LAT MT ROM Sources: International Agency for Research on Cancer: Globocan / UN World Population Prospects For both incidence and 5-year survival, the same ten countries rank highest and survival rates in Luxembourg, Italy, France and Belgium are rather better than in the other countries. With the exception of Slovenia, lower rates of both incidence and surviving patients are shown by the Eastern European member states. Other sources indicate that the 5-year survival rates vary from 23.1% to 46.7% of myeloma patients across the European countries 3. All of these observations should be used with caution, as they may be affected by differing reporting methods. It is likely that in countries with very high incidence rates, some patients with MGUS may be diagnosed as having myeloma; this could also explain their high survival rates and consequently a low incidence may mean missed diagnosis and/or poor survival. Patients with MGUS may be diagnosed as having myeloma; this could also explain their high survival rates and consequently a low incidence may mean missed diagnosis and/or poor survival. MPE Report on Myeloma Patient Perspectives 17

17 In the European countries that are not (or not yet ) members of the EU, several features are clear: Myeloma incidence in non-eu member states, 2008: New cases per 100,000 population Sources: International Agency for Research on Cancer: Globocan / UN World Population Prospects With the exception of Norway, Iceland, Switzerland and Croatia, recorded incidence is very significantly lower than in most EU member states The lowest level of recorded incidence (in Moldova and Albania) is only 16% of the highest non-eu country (Norway) and 13% of the highest EU member state Combining both sets of data suggests that a significantly lower level of diagnosis is achieved in most of the non-eu member states and in the Eastern EU member states apart from Slovenia 5-year survival rates for Iceland, Norway, Switzerland and Croatia are again significantly better than in the other non-eu countries and as for their higher recorded incidence rates, these four countries rival the better-performing western EU member states As for other European countries, the incidence of myeloma in Turkey, for example, is 7.1/ for males and 4.5/ for females. However, these data are not official and should be interpreted with caution**. Myeloma prevalence in non-eu member states, 2008: 5-year surviving patients per 100,000 population ICELAND NORWAY SWITZERLAND CROATIA SERBIA MACEDONIA MONTENEGRO BOSNIA HERZ BELARUS UKRAINE RUSSIAN FED MOLDOVA ALBANIA NORWAY ICELAND SWITZERLAND CROATIA SERBIA MACEDONIA BELARUS BOSNIA HERZ MONTENEGRO UKRAINE RUSSIAN FED MOLDOVA ALBANIA Sources: International Agency for Research on Cancer: Globocan / UN World Population Prospects Croatia was due to join the EU on 1 July 2013 ** Source: KANKO-Cancer Coalition of TURKEY (report 2013) 18 MPE Report on Myeloma Patient Perspectives

18 How is myeloma treated? Although myeloma cannot be cured, it is highly treatable in the vast majority of cases and the treatments available have made very significant advances in the last ten years. A wide variety of drugs and combinations is now available and the exact treatment plan should be decided for each individual. Aims of treatment: Following diagnosis, an initial course of treatment is agreed with the aim of reducing the level of myeloma cells, relieving the symptoms and complications, improving the patient s quality of life and the length of survival 7. After a period of remission, many myeloma patients suffer a relapse and the treatment may then be repeated or an alternative combination given. Patients often experience several periods of remission followed by relapse. Ultimately no further treatment yet available can stop the course of the cancer. Treatment of myeloma Treatment decisions are made on the basis of: o Stage and risk of myeloma o Individual patient s health and preferences o A balance of the benefits and side-effects of treatment o Prolonging life o Achieving the best quality of life for the patient o Logistics of available treatments. Treatment and management of myeloma is complicated and requires a multidisciplinary team, including orthopaedic, renal and pain specialists Choices for one patient may not suit another Choices are supported by clinical treatment guidelines from national health authorities or professional medical bodies and complement the legal framework provided by the EMA and the reimbursement decisions of national pricing authorities Many sets of guidelines and differences in the availability of medicines results in significant differences in treatment across Europe Available treatments: People given a diagnosis of myeloma will be treated according to the nature and stage of the disease, their age, fitness and preferences. Those diagnosed with MGUS or smouldering myeloma will not need treatment. Broadly, younger and/or fitter patients are first likely to be offered a combination of drugs, followed by intensive treatment. This consists of high-dose chemotherapy to destroy the myeloma cells, followed by replacement of healthy stem cells via a stem cell transplant from the patient or a tissue-matched donor. Older and/or less fit patients (over about 70 years) or those who are less able to tolerate the side-effects of intensive treatment will be offered a similar (although often with attenuated doses) combination of drugs, but no high-dose chemotherapy and stem cell transplant. A typical drug combination will most probably include: A chemotherapy drug to kill the myeloma cells (cyclophosphamide, melphalan or doxorubicin) A steroid to suppress inflammation (dexamethasone or prednisolone) MPE Report on Myeloma Patient Perspectives 19

19 Other newer anti-myeloma treatments including thalidomide (Thalidomide Celgene ),lenalidomide (Revlimid ) and bortezomib (Velcade ). These can improve the performance of chemotherapy drugs when given in combination 11, and prevent myeloma cells from surviving Pain relief as needed; usually non-steroidal anti-inflammatory drugs (NSAIDs) or, in the later stages, morphine Radiotherapy is sometimes the first treatment given to specific areas damaged by myeloma, as it can relieve pain more quickly than chemotherapy or other painkillers. It damages myeloma cells but also normal plasma cells, so it is only used to treat small areas that are causing particular problems 12. As well as treating the myeloma itself, it is important to prevent the myeloma from causing further damage to the bones, which is achieved with bisphosphonate treatment - zoledronic acid (Zometa ), pamidronate (Aredia ) or clodronate (Bonefos, Loron ). Response to treatment: If treatment is successful, the number of myeloma cells in the bone marrow will be reduced to a low level, allowing the bone marrow to recover, or even eliminating them. If the myeloma remains stable, it is said to be in remission 7. In order to check the progress of treatment, patients will undergo regular blood and urine tests to determine their paraprotein levels, which should be falling. They should also be experiencing less bone pain, reduced anaemia and a general improvement in health 7. Choosing between available treatments: Myeloma specialists will select the most suitable treatment for the individual patient and stage of disease; balancing the benefits and side-effects of the treatment. The aim is to prolong life and achieve the best possible quality of life for patients, making full use of a multidisciplinary team including orthopaedic and renal specialists and providing adequate control of complications and symptoms. Treating myeloma involves complicated choices for specialists, GPs and other healthcare professionals together with the patient in terms of the choice of drugs, duration of treatment, monitoring and the type and range of supportive care needed. The choices for one individual patient may not suit another, because of personal preference, age, genetics, general fitness and other medical conditions. Clinical guidelines Treatment decision-making is often supported and informed by the presence of clinical treatment guidelines from national health authorities or professional medical bodies that recommend appropriate treatment and care for myeloma patients. Recommendations contained within guidelines are exactly that: guidance rather than a set of rules, and are influenced by and must operate alongside the legal framework provided by the market authorisation of medicines by the European Medicines Agency and the reimbursement decisions of national pricing authorities. National guidelines are available for the entire myeloma pathway e.g. those from the UK Myeloma Forum and British Committee for Standards in Haematology or the Italian Haematological Society, and take account of the medicines available and reimbursed in that country 13,14,15,16,17. The US has its own guidelines 18,19, MPE Report on Myeloma Patient Perspectives

20 Broader international guidelines on specific aspects also come from the International Myeloma Working Group (IMWG) of the International Myeloma Foundation 21 and the European Society for Medical Oncology 22. Clinical guidelines are based on the aggregation of best available evidence or, in its absence, on consensus of expert opinion. They are intended to support and guide healthcare professionals in their work without replacing their knowledge and skills 23. Guidelines should ideally present the best, most up-to-date recommendations on treatment options based on review of current validated research 24. Their use can preserve professional autonomy and rationalise the increasingly complex sets of evidence into relatively straightforward recommendations and also protect doctors against criticism or even legal action 25. However, it is not always possible to account for every type of patient and treatment decision in myeloma and inevitably, some doctors will always have their own opinion so in practice guidelines are, often with good reason, not always followed. Together with the many sets of guidelines and the differences between the medicines available in different countries, this results in significant differences in treatment and care across Europe. Recent advances in research Many new developments in the treatment and management of myeloma over the last few years have had a significant impact on the way it is treated. Research is continuing to develop new treatments and to use existing treatments in a better, more effective way. Treatments for myeloma can be very effective at halting its progress, controlling the symptoms and improving quality of life. Use of the recently-developed treatments has made it possible to aim for a complete response 11 (i.e.control of the myeloma and a stable remission) in a larger proportion of patients than previously possible; meaning that myeloma is increasingly considered as a chronic condition in some patient groups. Myeloma is a highly complex and continually evolving cancer. At its core are a series of genetic changes that interact with each other, causing the myeloma to progress and ultimately become resistant to treatment. Studying the genetic changes that occur in myeloma cells is fundamental to understand the biological and cellular changes that drive the cancer. Most important has been the identification of a number of genetic alterations that influence a patient s prognosis. Recent advances in cytogenetic and fluorescence techniques and geneexpression profiling are now enabling these genetic alterations to be detected. The next 5 10 years is likely to see an upsurge in these discoveries being brought into clinical trials, leading to a clearer understanding of how treatments can be tailored to individual patients. Is myeloma costly to treat? Historically, the cost of myeloma treatment in the vast majority of cases was relatively cheap. However, the introduction of new treatments has brought with it a dramatic increase in costs both in terms of the individual price of drugs as well as how they are used. As a consequence, the costs of treating myeloma are among the highest of all types of cancer 26 with newer medications like bortezomib (Velcade ) or lenalidomide (Revlimid ) costing several thousand euros per month 27. These costs are currently coming under intense scrutiny, especially in terms of whether they deliver value for money. MPE Report on Myeloma Patient Perspectives 21

21 Summary Myeloma is a very complex cancer that is not yet fully understood. The available treatments can offer substantial benefit, especially the more recently-developed medications that enhance the performance of chemotherapy drugs when taken in combination with them. Genetic techniques under development also offer significant promise for the future. However, after a number of cycles of remission and relapse, still ultimately there is no cure, so that patients face a great deal of uncertainty. Taking all these different aspects into account, it is therefore important to ensure a holistic approach to treatment one that focuses on the person as well as the cancer. Mika s story Still well after 25 years! Although at age 20 Mika was given three years to live, that is now 25 years ago and today he is well, happy and able to do almost everything he wants (except play basketball). Recently he met his first myeloma consultant, who said Mika is still his youngest patient. As a young man he was in the Finnish army and began to experience pain in his leg when running. Walking down the stairs one day he broke his femur. My life had not even started, he says, when the doctor told me I had cancer. The break was due to a plasmacytoma. At that time (in the mid-1980s) it was very hard to find information, with no myeloma associations or internet. Mika took a course for cancer patients, but because myeloma was so rare, there was little specific information. He felt it was hard to ask questions of the doctors and nurses. Mika had surgery to remove the plasmacytoma, followed by radiotherapy; and this was repeated in In 2008 he was given chemotherapy for myeloma and had his stem cells harvested and frozen for a transplant, but so far that has not been needed. I know and I hope that some day a transplant will allow me to continue my life; it s easy for me, knowing that the stem cells are there and I don t need some from another donor. He feels that his myeloma treatment in Finland has been excellent, but psychological support is not so readily available. Instead, social and emotional support and the information to help patients to cope with everyday life have come mainly from the voluntary cancer associations. In Finland, the government plan of 2011 includes a national cancer centre with important functions for the patient associations. Mika is starting to work full time for the cancer association and considers himself a lucky man. To others with myeloma, he says: If you know a lot about your disease, it will help you a lot. Better understanding of the behaviour of the disease can help manage the uncertainty and alleviate unfounded fears. I think being positive is the only way to live, trying to have a normal life, going to work, and being with my wife and my dear friends. Mika Peltovaara Myeloma patient, Finland Better understanding of the behaviour of the disease can help manage the uncertainty and alleviate unfounded fears. Mika 22 MPE Report on Myeloma Patient Perspectives

22 2. Best practices in the treatment and care of myeloma are they being achieved?

23 2. Best practices in the treatment and care of myeloma are they being achieved? People with a complex cancer like myeloma need very specific input from all the different medical, scientific and social members who together make up a multi-disciplinary team that works in a co-ordinated, holistic way. This chapter looks at what those needs are and reveals major shortcomings in many countries of Europe. Examination of the barriers preventing access to the best standards of care shows late diagnosis, poor access to the most recent treatments, to well-informed medical care, clinical trials and psychological support alongside differences due to geographical location, age and socioeconomics. Key points Rates of survival appear to reflect a variation in diagnosis, treatment and care between European countries The main barriers to optimal care are: o Delayed diagnosis o Poor access to authorised treatments o Waste of resources o Regional differences o Variation in reimbursement policies Older patients are more likely to have other medical problems in addition to myeloma 5-year survival is much greater in younger patients Poorer outcomes are seen in people with lower incomes, lower levels of education and by country of residence Culture may have a bearing on access to treatment and support. Many people find it harder to question and therefore harder to seek access to more information, latest treatments, clinical trials and/or psychosocial support. What should patients expect from their treatment and care? Although not exhaustive, this list highlights patients expectations about what constitutes best treatment and care. Up-to-date treatment: Significant advances have been made in the treatment of myeloma over the last ten years, including availability of new newer proteasome inhibitors e.g. carfilzomib and immunomodulatory drugs, e.g. pomalidomide. These new possibilities promise significantly better results than traditional approaches. Given the relapsing and remitting nature of myeloma alongside the fact there is currently no cure, patients need access to the best treatments that research can offer them. 24 MPE Report on Myeloma Patient Perspectives

24 Information: Initial shock and numbness at the time of diagnosis may be mixed with anger (why me?), denial, or relief at being given a reason for hitherto unexplained symptoms. The first need is for information, which must be understandable (not too technical) and up-to-date. Information that applies directly to the individual and to the stage of myeloma enables patients to understand it more fully, to play an informed part in treatment decisions and to feel more in control. However, not every patient wants all possible information; the important thing is that they have the level of information that they need 28. Living with myeloma I want to know everything about it I believe it is important that newly diagnosed patients, still trying to overcome the shock of their diagnosis, are put in touch by the hospital with those who have gone through a stem cell transplant and have led a normal life for several years before needing further treatment. I decided two objectives soon after my myeloma diagnosis twelve years ago I was determined to see this cancer off, and to study it and understand the nature of the disease and its treatments. I knew nothing about haematology but I started to access the latest publications on the internet and attended many myeloma seminars. The knowledge I acquired became a powerful attribute to my fight against myeloma, and after years of study I became accepted by some as an expert patient. Stewart McRobert Myeloma patient, UK I was determined to see this cancer off, and to study it and understand the nature of the disease and its treatment. Stewart Effective communication: As well as information, patients need effective communication with their doctors and enough time to digest the options. No action may be needed beyond regular monitoring, but it is important that patients understand why that decision is reached, so they do not feel as if nothing is being done. Psychosocial support: Patients are vulnerable to depression and should have access to regular assessment and psychological support or counselling. It is well established that the emotional support of partners, family and friends and any other carers is essential to help them to adjust and cope 29. Partners and other carers have a crucial role and offer a reason to go on fighting 29 (often involving great personal stress). Ideally this should be matched by practical measures including efficient arrangements from hospital authorities to enable regular, stress-free attendance for treatments and assistance from social services and complete access to all relevant social security benefits. Hard evidence is scarce on the availability of psychosocial and emotional support, but anecdotal evidence suggests that it is rare, especially in Eastern Europe. MPE Report on Myeloma Patient Perspectives 25

25 Carers need support too: The emotional burden on people who care for myeloma patients often their partner or another family member is sometimes even greater than that on the patient 5. A recent study across four hospitals in the UK showed that almost half of myeloma patients partners (48.8%) reported signs of anxiety and 13.6% showed signs of depression 5. Carers have many of the same information needs about myeloma and its treatment as patients, but also many unique ones that the patient may not share and may not want to know about. Healthcare professionals should ensure that carers and family have the support they need to manage continuing side-effects or complications, lack of local health services as needed and the changes that myeloma has caused to the patient 5. Patient organisations are offering a very supportive base for carers in many European countries, especially in providing forums for comparing notes with other carers. The Netherlands myeloma association, for example, supplies extensive and diverse information for both patients and carers. Access to expertise within a multidisciplinary team: As well as a specialist haematologist to propose the most appropriate treatment for the myeloma itself and for any orthopaedic or renal complications, patients need the regular support of different members of a multidisciplinary care team. Members of this team will commonly include a specialist myeloma or haematology nurse, a radiotherapist, an orthopaedic surgeon, a renal specialist, a physiotherapist, a dietician and palliative care staff. Access to a myeloma nurse specialist: Trust and confidence in the team members is essential 29 and among them, specialist nurses are especially important. Patients report easier communication with nurses than with their doctors, because of less time pressure and a better understanding of the daily impact of myeloma. Specialist nurses can also help in practical ways. Access to treatment when needed: The decision to treat or not to treat immediately is an important one. Treatment, if needed, will depend on the stage of myeloma, the presence or absence of symptoms or complications and general health. Ideally, it should be tailored to the individual in terms of their age, fitness and other medical conditions. In years to come it may be possible to offer truly personalised treatment, taking account of individuals genetic makeup (see page 46). The opportunity to take part in research: Many patients also welcome the chance to participate in clinical trials of new drugs. These offer the dual benefits of possibly being helped by tomorrow s drugs today and also receiving intensive monitoring while the trial is running. Shared decision-making: It is important that patients feel their views and preferences are taken fully into account in decisions about treatments. Treatment can take various routes, many of which involve a balance between benefit and side-effects. Effective communication and shared information between doctor and patient should take into account all the medical and psychological factors, so that both can arrive together at the best overall course of action. CMWP Contactgroep Myeloom en Waldenström Patiënten 26 MPE Report on Myeloma Patient Perspectives

26 The last days of life: The time will come when the myeloma has progressed so far that no treatment will alter its course 30. At this time, extreme sensitivity is needed on the part of the doctor in making the outcome clear to the patient. The care pathway should ensure that the patient s preferences are being met and that the palliative care team, social services and primary care team are monitoring the physical and emotional needs of both the patient and their family. Inappropriate treatments should be stopped and major symptoms, particularly pain, controlled to keep the patient as comfortable as possible 14. There are a large number of ways and a broad spectrum of how patients come to terms with the last days of life. For example, while some patients are able to draw comfort from hope, spirituality, family support 29. others may become withdrawn, distant and tearful 30. Such reactions may be because they are themselves unable to come to terms with the end of life, or because of difficulties in talking openly about it with the family and a wish to protect them. Family members may choose to focus on the present time, rather than the future, because it is too upsetting 30. For both patient and family, emotional support is needed just as much as effective communication 30. Christa s story A positive outlook is everything It is exactly seven years since Christa was diagnosed with myeloma, after investigation for severe anaemia. Since then she has endured a succession of treatments that have given her remission and relapse, over and over again. Her first two treatments were transplants with her own stem cells, which gave her a partial remission and allowed her to return to work for a year. But when the relapse came, Christa s doctors were unable to harvest her stem cells. Treatment with thalidomide left her feeling extremely tired and low, so it was replaced with Velcade and a good remission followed. At the next relapse, Christa agreed to an allogeneic transplant with stem cells from her sister, who fortunately was a good match. The time after the transplant was the hardest time of all, Christa says; not knowing if the transplant would work, not able to eat, or go out or see people in case of infection. But other things did help including some homeopathic therapies, yoga, meditation and breathing techniques; also sports when she was well enough again. Most importantly, I learnt the cancer cells are not my enemy. I had to consider them my friends that wanted to tell me something, and I had to find out what it was. I had to change my personality a bit and try to live with more consciousness as every day could be the last day. Myeloma cannot be cured so you have to think about that; I read a lot about philosophy and that helped me. Christa has worked with the self-help groups of her myeloma patient association for years, since soon after her own diagnosis. Before joining she thought she might hear too many bad things, but she found it very helpful to exchange experiences with other patients. After a sustaining therapy with lenalidomide, Christa had a relapse with a solid plasmacytoma in the liver, but this has been eliminated recently by radiotherapy treatment. It s a neverending story, she says. Every myeloma case is different. My advice to every patient is inform yourself. Christa Kolbe-Geipert, Myeloma patient, Germany Every myeloma case is different. My advice to every patient is inform yourself. Christa MPE Report on Myeloma Patient Perspectives 27

27 What is lacking in myeloma treatment and care? The patients view Research has shown that many myeloma patients have a lower quality of life than those with other forms of blood cancer 5,31. A recent UK study 5 revealed that one quarter of myeloma patients investigated could describe care needs that were not being met, while their carers reported similar care needs and a level of distress even higher than that of the patients. The needs expressed 5 were: Health-related, e.g. pain interfering with daily life, reduced physical functioning, fatigue, side-effects Emotional/psychological, e.g. anxiety about treatments and side-effects, anxiety about the burden on carers, anxiety about refractory myeloma or relapse, depression Practical, e.g. access to hospital parking Financial, e.g. access to life insurance Social, e.g. a lack of knowledge and understanding about myeloma among the general public In addition to the needs recorded in that study are the difficulties of achieving shared decisionmaking between patient and doctor. What is preventing myeloma patients from receiving the best standards of treatment and care? Clearly not everyone with myeloma in Europe is receiving the best possible treatment and care from the outset. These are the main barriers: Delayed diagnosis: As myeloma has such a devastating physical impact, early diagnosis is important in order to benefit from treatment and prolong life of an acceptable quality. In some EU countries, patients commonly report having waited up to two years before their myeloma was diagnosed. During that time, patients can suffer fatigue, pain and anxiety and a reduced quality of life. GPs and orthopaedic specialists commonly see the symptoms of myeloma, such as back pain, but a recent survey in Belgium found that the a GP is likely to see only one or two myeloma patients in a 30-year career. Delay means that the patient s condition is worse at diagnosis and is more likely to be suffering bone fractures, renal problems or infections that can make delivering chemotherapy more difficult. Information is needed to help alert GPs and orthopaedic specialists to the very small proportion of their back pain sufferers who may have myeloma and to raise awareness of other symptoms possibly due to myeloma. Ideally people with suspected myeloma should benefit from a rapid-referral system for specialist diagnosis. Poor access to authorised treatments: Anecdotal evidence shows that treatments approved by the European Medicines Agency (EMA) are often not available equally across Europe or only available with restrictions. The variation in treatment within and between different countries results from different doctor preferences and healthcare systems, level of state or private sector funding and also from the varying national reimbursement policies. For example, Revlimid has received approval for marketing authorisation by EMA as a second-line treatment (i.e. after the first relapse), in combination with dexamethasone. However in Belgium, it was initially only reimbursed for third-line treatment after relapse while 28 MPE Report on Myeloma Patient Perspectives

28 under treatment with Velcade and for eight cycles of treatment. Further, if the patient was not in at least partial remission after four cycles of Revlimid, reimbursement of this medicine was stopped. The doctors could not prescribe Revlimid according to the European authorisation. The Belgian patient organisation has worked with doctors and the pharmaceutical company to advocate for reimbursement criteria that allowed Belgian patients to benefit from the medicine, as recommended by the EMA. In some Eastern European countries the reimbursement decisions relating to myeloma treatments are described by patient organisations as catastrophic. In Hungary, both Velcade and its generic equivalent are only reimbursed for three cycles, and Revlimid is only a dream. The out-of-pocket cost of Revlimid for patients themselves, at 6-7,000, is too high for most patients. France, Germany, Belgium and most other Western European countries have more generous reimbursement systems. Brain drain: The difficulty that doctors face in attempting to provide care in Eastern European countries with less advanced treatment options is causing many to leave in search of a more favourable working environment where they have access to the most up-to-date treatments. For myeloma patients in those countries, this makes the prospects even worse. Regional differences: The standard of care available varies according to where patients live. University hospitals, for example, have myeloma specialists who may be engaged in current drug trials and are fully aware of the latest findings on the uses and advantages of innovative treatments. In comparison, patients of rural, local hospitals are often in the care of general haematologists or oncologists who may not be fully informed on the latest research developments, clinical trials and complexities of myeloma. Geography, age, socioeconomics and culture: Myeloma mainly affects people in the older age groups, with fewer treatment options and access to clinical trials. They are also more likely to suffer other medical problems, which would weaken their overall condition 32. Five-year survival is much greater in younger patients 32. MPE Report on Myeloma Patient Perspectives 29

29 Johan s story Lucky to have the medical costs covered Johan lives in Belgium, and has had myeloma for 15 years. Out of the treatments available in the early years, he was only treated with bisphosphonate. After five years he was given VAD induction treatment, to be followed by an autologous stem cell transplant, but the transplant could not proceed as the induction therapy was less than successful. The myeloma remained stable for seven years, but radiotherapy was needed for two plasmacytomas and again later for another that was affecting the pelvic bone. A treatment according to the Velcade -dexamethasone schema (4 cycles) was started, followed by cyclophosphamide, growth hormone treatment and a further stem cell transplant. After all these different treatments, he went onto consolidation treatment with thalidomide alone and then in combination with Velcade -dexamethasone. I am very satisfied with the medical care I have received, says Johan. All the treatments have been undertaken in consultation with my doctor, and an added plus is that through my work, I have additional insurance for medical expenses. However, the criteria for treatment of myeloma and the repayment terms of the health insurance are different from country to country. Johan Creemers Myeloma patient, Belgium the criteria for treatment of myeloma and the repayment terms of the health insurance are different from country to country. Johan 30 MPE Report on Myeloma Patient Perspectives

30 Five-year relative survival rates by age, England, Male Female Relative Survival Period of Diagnosis Source: Cancer Research UK Within the last ten years, an increased risk of myeloma and poorer outcomes have been shown in people with lower incomes or a lower level of education, although these differences were not detected by earlier studies 32,33. Distance to medical treatment may delay or deter rural residents from seeking diagnosis and treatment; also people from lower socioeconomic groups are more likely to present with more advanced myeloma. It is possible that those in lower socioeconomic groups may less frequently seek diagnosis and receive less extensive investigation from their doctors 33. It has been shown that older people, women and those from socially disadvantaged areas have a lower referral rate for hip pain 34. This may be related to more difficult access to specialist care, or practices in disadvantaged areas having a higher workload and more patients with a higher number of comorbidities 34. Culture may also have a bearing on access to treatment and support. Doctors have traditionally held a position of knowledge and authority which many people, especially in the older age groups, those without a strong education and those in the former communist countries, find difficult to question. It is much harder for these people to seek more information, or access to the latest treatments, clinical trials or psychosocial support. Unmet psychosocial needs: Myeloma patients are known to suffer pain, fatigue and sleep disturbance; all of which will have an impact on everyday life. This is frequently linked with anxiety and depression, yet from the accounts given by patients, medical care tends to focus on the physical aspects of the cancer. Only some countries appear to address emotional or psychosocial needs effectively; see the Netherlands example on page 70. MPE Report on Myeloma Patient Perspectives 31

31 Summary It is clear that in many ways, myeloma patients in Europe suffer because of the rarity of their cancer. Health systems and health budgets are inadequate to meet their needs for access to up-to-date treatment and to all the medical disciplines that could help them, particularly in Eastern Europe. There is also a great need for education of healthcare professionals in effective communication and awareness of the urgent need of patients for information, the opportunity to play a real part in their treatment decisions and to participate in appropriate clinical trials. Recommendations: towards better myeloma care in Europe For doctors, nurses and the wider healthcare team: Ensure patients have access to the most up-to-date treatments in order to control their disease and offer the longest possible period of control, with optimal pain relief to enable a good quality of life Facilitate quick, individual treatment decisions that are tailored to the individual, taking the patient s views into account Ensure each patient has access to a multidisciplinary care team including orthopaedic and renal specialists as well as a haematologist Generate stronger links between primary care and specialist centres Ensure all suitable patients are made aware of all current clinical trials and given the opportunity to participate if they wish Take care to ensure effective communication with patients and their families, and to give the patient sufficient time for dialogue Psychological and psychosocial support and counselling should be available to help all myeloma patients to deal with the emotional impact and with the stresses of daily living Provide access to as much, or as little information as patients want. This is especially important at diagnosis. Also provide tailored information and emotional support for carers For healthcare policymakers: Develop and implement national myeloma plans and awareness campaigns Establish uniform care standards and a faster drug authorisation process Support improvements to education for healthcare professionals, including GPs, on diagnosis, symptoms and new treatment options for myeloma Give priority to the elimination of differences between urban and rural treatment options 32 MPE Report on Myeloma Patient Perspectives

32 3. Building a successful partnership with healthcare professionals

33 3. Building a successful partnership with healthcare professionals The patients and experts interviewed in the preparation of this report were of one voice in stressing the massive importance of good communication between myeloma patients and their doctors and other healthcare professionals. Poor or ineffective communication has a major impact on how well patients are able to cope. This chapter explores what effective communication can achieve, what stands in the way of good two-way partnership, and how the relationship can be nurtured to the benefit of both partners and principally that of the patient. Key points The ideal is a trusting, open partnership, with emotional support and open communication between patient and healthcare professionals GPs and specialists should be open to a joint decision-making process and empower their patients to share control of their treatment if they wish Treatment decisions should be made jointly and take account of each patient s priorities and personality Setting realistic short-term goals and frequent review helps the patient s ability to cope Treatment decisions should be reached only when the patient has had time to digest and absorb all relevant information and options Practical support for patients needs to be offered, and significantly strengthened in many countries Information given orally about diagnosis, treatment and side-effects should be timely, well communicated and supportive; and supplemented by online or written information What do patients want from their doctors? Patients feel positive towards their healthcare professionals when they appear to have an interest in their care or ask the right things 29. They can also feel intimidated by the medical language, and are afraid of appearing stupid. From the doctor s viewpoint, the main objective is usually to maximise the duration and quality of life for their patients. However, as well as pursuing those practical medical aims, the doctor must also be professional, honest, a good communicator and provide emotional support. Engaging in general conversation, sharing information and acknowledging patients knowledge in order to foster a more equal relationship can all help to build trust between doctors and patients 35. Setting out realistic, short-term and frequently reviewed goals, e.g. evaluating, prioritising and deciding on which actions to take, is a vital part of coping and helps patients to gather the strength to face the uncertain future 36. Patients, on the other hand, are often as interested or more so in the quality of their life, rather than how well the treatment is progressing as shown by the level of biochemical markers. Some aspects of quality of life can actually be better than it was before diagnosis, as the diagnosis can drive people to address what is most important to them. 34 MPE Report on Myeloma Patient Perspectives

34 Shared decisions none of the doctors have undergone chemotherapy or a transplant themselves. That is why a patient is a very useful source of advice for the doctor, in the same way as the doctor is an irreplaceable consultant for the patient in the treatment of multiple myeloma Slovak Myeloma Society Patients Club Again, the treatment decisions should take account of each patient s priorities and character. While it will suit one person to seek less intensive or palliative care, others will call for every treatment you ve got. In addition, the diagnosis may end a long period of worry about what is causing the patient s health problems, enabling a more definite approach, and treatment may relieve pain both of which can improve overall quality of life. The impact of myeloma treatment on the practical aspects of life may also contribute to feelings of anxiety and may raise additional questions and issues that need support beyond the scope of healthcare professionals. Patients will need to consider: will I be able to continue working/keep my income/keep my pension/ get travel insurance, and how will my family be affected? Practical problems like these contribute significantly to the emotional burden of myeloma. Support from patient organisations and social welfare bodies is essential to help patients deal with these issues and in many countries needs to be strengthened significantly. In a more sensitive area, couples affected by myeloma, but considering having children, will need extra information and support and guidance regarding the risks to fertility with some treatments, as well as pregnancy prevention strategies during treatment with thalidomide or Revlimid (see page 61). In addition, and very importantly, loss of a family member to myeloma, especially a child losing a parent, will require support and possibly counselling for the affected family members. What issues get in the way of effective doctor-patient communication? Shortage of time: One of the barriers to successful communication with hospital specialists is lack of time, although this need not be a problem if both specialist and patient are able to use the time effectively. Trust: It is vital that patients trust their doctors 29 and that the time and expertise are available and used effectively to give the right level of information and support. Providing the right information, accounting for the benefits and the risks of the treatment, supports informed decision-making, better adherence, less distress and a greater sense of control; plus satisfaction with the care received 37. Feeling overloaded with information can lead instead to confusion and worry 29. Communication skills are rarely taught in traditional medical training: Doctors ability to communicate with patients varies considerably. Ideally, training on communication skills should be added to the curricula of undergraduate medical schools. In recent years, continuing medical education approaches e.g. interactive online modules are becoming available to enable healthcare professionals to improve their skills 38. MPE Report on Myeloma Patient Perspectives 35

35 For some other chronic conditions, a range of tools is available to facilitate communication and understanding between doctor and patient. These include use of wellbeing indexes e.g. WHO- 5, to help define patients level of contentment or anxiety 39. Patients can be unsure how to communicate: Faced not only with a major shock at diagnosis, but also uncertainty over the future as a whole and the individual ordeals they may have to endure, it is no surprise that patients often feel overwhelmed by their situation. They need to absorb a lot of information; much of it quite complex and full of unfamiliar words, at a time when they are least able to formulate meaningful questions and suggestions. This uncertainty is at the root of the common advice from people who have had myeloma for some time: to gather information and to become as well-informed as possible, but it is not an easy path to take. A full partnership Professional, honest communication, a holistic needs assessment, and setting out realistic, short-term and frequently reviewed goals are crucial in discussions between patient and doctor. This relationship enables a trusting partnership and equal participation in treatment and management decisions a vital way for the patient to cope and gather strength when facing an uncertain future. Treating the person, not the myeloma Trust between patient and doctor is essential because of the many decisions to be made, ideally in partnership. This is not only about deciding on the treatments being prescribed; the doctor should ideally consider the whole person and how he or she is coping with the emotional stress of having myeloma. In the UK, the National Institute for Health and Clinical Excellence (NICE) recommends that all cancer patients should have a holistic needs assessment at diagnosis, after initial treatment and during follow-up 40. A quantitative tool such as SPARC should be used, which enables the patient to rate their pain, psychosocial, spiritual, financial and other issues, using a 4-point verbal or Yes/No rating scale 41 ; or the distress thermometer which rates overall distress on a numerical scale 42. Regular holistic assessment is an ideal that is met to a varying extent in the different countries of Europe. Attention to the patient s preferences and state of mind goes a long way to improving communication. This better sense of trust and understanding will also have practical benefits, for example patients compliance will improve if they feel that the doctor understands and is sympathetic. Key situations where extra understanding is significant are: Timing of diagnosis: Before receiving the diagnosis, the patient may have endured months with vague symptoms of fatigue and bone pain; possibly compounded by feelings of being a time-waster. Once diagnosed, they may also feel cheated by the time wasted and by not having had treatment during that time. 36 MPE Report on Myeloma Patient Perspectives

36 Diagnosis: This is an extremely traumatic experience for most and needs time, care and attention to the needs of the individual and acknowledgement of the seriousness of the news. At the first meeting, the patient is unlikely to be able to take in much detail, so the messages should be kept simple and supportive. It is important to stress that while myeloma is incurable, it is eminently treatable, that the prospects are improving rapidly and there is some hope for longer term survival, particularly for younger patients. Spoken input must always be supplemented by providing written or online information, at different levels of detail. Patients in our patient group report that doctors are very good at the medical aspects, but sometimes neglect the emotional side. A myeloma patient is never well again the myeloma will be there for the rest of his/her life. That asks for a very specific psychological approach. Greetje Goossens, representative of the Belgian patient groups and board member of MPE Treatment choices must be right for the individual: In discussing and deciding on the most appropriate treatment, patients need enough information about the options and their benefits and side-effects. Importantly, they also need enough time to digest it before reaching a shared decision with their doctor. They need a good discussion about the treatment options, the aims of each option and likely side-effects. Shared decision-making: If the doctor is not open to the idea, it can be overwhelmingly difficult for even a patient who is well-informed about myeloma to try to establish a debate about potential treatments. However, in general, patients need to become more empowered; developing the confidence and knowledge to seek a second opinion or to ask to be referred to a specialist treatment centre. Some patients report they had to battle their way through the system ; having to seek several medical opinions before being offered certain treatments. Patients should also be able to choose between treatment options, if they want to. Their views may also change as their myeloma progresses, e.g. if they become more ill or if personal circumstances change. Not everyone wants all the details: Not all patients want to be actively involved in treatment choices, preferring to leave the details to the doctor. This view is particularly found in older patients and those in particular countries (as in Eastern Europe) or populations (e.g. Afro-Caribbean or Asian groups) where the accustomed culture is that the doctor makes the decisions. Summary Effective doctor-patient communication is particularly important in order that patients retain as much control of their well-being as possible. Myeloma brings many challenges and if both patient and doctor are able to share both information and understanding that will contribute greatly to patients peace of mind and their quality of life. MPE Report on Myeloma Patient Perspectives 37

37 Recommendations: Partnership with healthcare professionals For patient organisations: Work to define patient expectations and needs when communicating with their doctors and other healthcare professionals Encourage individual patients to develop the knowledge and confidence to work in partnership with their doctors in deciding on treatment; also to be able to challenge recommendations and to seek second opinions as a standard option Recognise that it will take time to change attitudes in both patients and doctors Work with social security agencies, public awareness campaigns and the media For doctors associations and teaching hospitals: Focus more on holistic care for myeloma patients, with as much attention to emotional wellbeing as physical therapy Urgently raise awareness of myeloma in young doctors entering primary care, in order to reduce unacceptable delays in diagnosis Promote uptake of accreditation through the European Hematology Association for centres offering training in blood cancer treatment, and enable implementation of up-to-date treatments and policies Devote greater attention in doctors training/continuing medical education to building communication skills, especially in conveying diagnosis, the relative risks and benefits of treatments, and providing the appropriate level of information for the individual patient For healthcare policymakers: Support improvements in doctors training to include better communication skills and attention to the emotional as well as physical needs of patients Give priority to more satisfactory provision of emotional and psychosocial support to both myeloma patients and their carers 38 MPE Report on Myeloma Patient Perspectives

38 4. Patients needs should be at the centre of research MPE Report on Myeloma Patient Perspectives 39

39 4. Patients needs should be at the centre of research Although a great deal is now known about myeloma and its effects, further research is essential to make progress towards establishing its causes, alleviating its symptoms, limiting its progress and ultimately finding a cure. As a rare cancer, myeloma research has suffered from limited resources because of the relatively small numbers of people affected compared to the major chronic conditions and other forms of common cancer. Due to the fact that myeloma has such devastating impact, patients are keenly interested to support research and to have input into research priorities. This chapter examines the challenges and constraints facing research in myeloma and what patients priorities are for research, and the role they and their representative organisations can play to influence the agenda. Key points No current cure for myeloma means continued research is needed to find its causes, new effective and safer treatments and ultimately a cure High quality trials are needed to ensure statistical validity and best use of scarce resources Many patients are keen to take part in clinical trials and research All patients should be made aware of clinical trials and given the option to take part if feasible Policy-makers should be continuously monitoring and benchmarking research to achieve best possible outcomes Patient organisations should be involved to identify research priorities and objectives to help ensure that limited resources are directed towards patients priority areas Patient groups and individual patients should advocate better collaboration and coordination of research projects, to reduce duplication, make best use of available resources and deliver research outcomes Interpretation and application of legislation needs to be simplified and standardised across Europe the current proposal for an EU regulation on clinical trials gives the opportunity to ensure simpler procedures and more transparency, which should reduce the regulatory burden on trials and encourage more to be conducted in Europe Patients views on clinical trials should also be reported and taken into account Take into account the needs of myeloma patients Put me, and others, back in a durable remission where we are symptom-free and treatment-free. How about eliminating peripheral neuropathy side-effects from treatment drugs? Get rid of all that myeloma bone pain, the broken bones, the back problems. These things just debilitate so many myeloma patients over time. Oh, and just cure the disease; that will take care of everything. I m not holding my breath for that. Lou Ganim, Myeloma patient, USA* * first published in Myeloma Beacon, 17 July MPE Report on Myeloma Patient Perspectives

40 Why is research so critical for myeloma patients? Once diagnosed with myeloma even with smouldering myeloma which has no symptoms patients know that there is no cure. As myeloma is a relapsing and remitting cancer, there is a pressing need to understand the mechanisms that trigger its stop-start stages of progression. Treatment can do a great deal to relieve the symptoms and temporarily halt the progress of myeloma and research in the last ten years has resulted in the development of lenalidomide (Revlimid ) and bortezomib (Velcade ) that can improve the performance of chemotherapy drugs when given in combination. More new treatments are keenly anticipated. In addition, some of the traditional treatments themselves have unpleasant side-effects. For these reasons, continued research is urgently needed, as myeloma patients are all working on a limited timeframe. That is why they are especially keen that the rapid advances of research of recent years are translated into treatments. What types of research are being undertaken? Research is continuing on potential new treatments and to assess interventions to reduce toxic side-effects from existing drug regimens. Other types of research focus on the impact of myeloma on the quality of life of patients; or assess the true and economic value of treatment to patients, health systems and society as a whole. This is often done through a process called Health Technology Appraisal. Genetics is a vital area of current myeloma research; focusing on defining the factors responsible for the onset and progression of myeloma, identifying its sub-groups and the factors responsible for both relapse and refractory myeloma (myeloma that no longer responds to a specific treatment). It is also likely that a person s genetic makeup influences their susceptibility to environmental risk and their response, but much more work is needed in this area 44. There is no single genetic change that pinpoints the tendency to develop myeloma 45, but it is becoming possible to stratify treatment more closely to individual patients 46. Here, research and development of genetic techniques is as important as development of new drugs. Among recent advances in these techniques are cytogenetic analyses of myeloma cell chromosomes, which can detect any sections that have become broken and rejoined to other chromosomes (translocations), or where myeloma cells have an abnormal number of chromosomes or other abnormalities 47. Fluorescence in situ hybridisation (FISH) studies of bone marrow plasma cells can detect translocations and other chromosome changes too small to be detected by other cytogenetic testing 47, identifying patients with high-risk myeloma. Gene-expression profiling (GEP) is another technique capable of classifying patients as high-risk or low-risk 45,46. All of these technologies enable a more accurate prognosis to be developed and appropriate care selected. Those at high risk (with expected survival of less than three years) could justify more intensive treatments like allogeneic stem-cell transplant or trials of innovative experimental drug combinations 46. Those at low risk (likely to survive for 7-10 years or more) could more suitably be offered less aggressive treatments that focus on minimising toxic side-effects and optimising quality of life 46. However, the decision is not clear-cut and the approach should be decided on the basis of the individual patient s needs. In any case, these tests are difficult to interpret and need rigorous quality control which is possibly not yet achievable on a wide scale 45. It is likely that in the future, GEP techniques can be developed so that it will become possible to identify specific treatments that will get the best response from a given patient 45. MPE Report on Myeloma Patient Perspectives 41

41 Clinical research, e.g. on the mechanism of action of a potential new drug or to assess the action of drug combinations, follows the following stages: Pre-clinical laboratory research: This uses myeloma cells in culture and animal models to establish if a drug is likely to work, without causing major side-effects. If laboratory results indicate that a drug candidate is promising and safe, it will undergo clinical trials. These can also investigate the use of new combinations of drugs or new treatment regimens. Clinical trials/development: Clinical trials are conducted to test the safety, efficacy of treatments or combinations of treatments; first in small pilot studies and later in trials involving many hundreds of people or even more. They are carried out according to strict procedures (protocols) which have been approved by an independent research ethics committee to protect the interests of the participants. Currently a wide range of trials is under way in Europe 48, investigating the role of: current myeloma treatments e.g. bortezomib (Velcade ), thalidomide, lenalidomide (Revlimid ) newer proteasome inhibitors e.g. carfilzomib and immuno-modulatory drugs e.g. pomalidomide novel targeted therapies e.g. antibodies, signal transduction inhibitors, targeted radiotherapy and vaccine approaches supportive care issues: bone complications, infections, pain Clinical trials are usually carried out in hospitals and may be funded by a public sector research body (e.g. the EU s Research Framework Programmes, the UK Medical Research Council), by a private foundation (e.g. the International Myeloma Foundation) or researchfunding organisation (e.g. Myeloma UK, the Multiple Myeloma Research Foundation or the European Myeloma Network) or by a pharmaceutical company. Since the mid-1990s, the EU has contributed funding to some 25 collaborative research projects on aspects of myeloma under the Seventh and earlier Research Framework Programmes. Current EU-funded projects relevant to myeloma are examining the molecular causes of drug resistance (led by a research team in Belgium), optimising therapeutics in high-risk myeloma (Austria), and cancer-associated bone disease (UK) 49. Real-world data A further aspect of research is the study of real-world data and the analysis of myeloma registries, which collect data on the epidemiology of myeloma in the population as a whole. Analysing registries can be the source of wider understanding of how medical conditions affect larger numbers of people especially important for a rare disease like myeloma. They give researchers the opportunity to examine possible relationships between the incidence and prevalence of diseases, and environmental or population factors. What are the challenges and constraints facing research in myeloma? Funding and prioritisation: It is vital that research is directed towards efforts that will make the greatest improvement to the lives of myeloma patients. Pharmaceutical industry researchers in particular, who account for 79% of the trials done each year in the EU 50, should focus on developing research projects of the highest quality; large enough to ensure statistical validity, and with real potential to make a difference to patients lives. 42 MPE Report on Myeloma Patient Perspectives

42 Patient organisations can help by identifying priorities and objectives and by making the case for adequate, prioritised funding for research studies in both the private and public sectors. The objective of achieving the best possible outcome from investment in research should be continuously monitored and benchmarked by health policymakers. Legislative control: Clinical trials in the EU are regulated by the requirements of the EU clinical trials directive 52 which is designed to ensure that no harm comes to the participants and that the outcomes are scientifically validated. However, a recent review of the directive has shown that its requirements have been interpreted and applied differently in different member states; they have doubled the cost of running trials since before it came into force, and the number of trials being conducted fell by 25% between 2007 and The market economy fails to provide adequately for research in all cancers. This is a key area where Europe can add value by supporting academic and translational research. We can use funds from the Seventh Framework Programme to encourage research and innovation in the areas of primary prevention, screening and early detection, and new anti-cancer medicines and treatments, particularly in the realm of rare and difficult-to-treat cancers which may be considered unprofitable by industry we can revise the political framework to stimulate further research. Adamos Adamou MEP, Co-Chair of MEPs Against Cancer*, 10 April 2008 These difficulties led to a new measure being proposed in July this time a regulation. As a regulation, this will have direct legal force in the member states, unlike the previous directive which had to be implemented by national legislation; often leading to different interpretations in the different countries. The proposed regulation will offer simpler procedures and more transparency about recruiting; it should come into force in The European Commission intends that this change should reduce the procedural burden on trials investigators having to meet varying requirements in Europe, and encourage more trials to be conducted in Europe. Reducing duplication: Research into cancer (of all types) and its treatment is diverse and fragmented across the European Union. The European Commission has called for collaboration and better co-ordination of research in order to cut down on duplication and enable faster progress 55. Its own Seventh Research Framework Programme is funding several collaborative clinical trials 56. Translating research results into clinical practice: Patient organisations can support the best implementation of research by highlighting to government agencies the most promising outcomes from clinical trials, so that research findings can rapidly be adopted into clinical practice. While this should not be the responsibility of patient organisations, initiatives from them can only be a step in the right direction. Rare disease research: As one of the rarest forms of cancer, development of myeloma treatments has suffered from the relatively small market for its treatments. Low patient numbers challenge trial organisers to assemble statistically valid results. However, patient advocacy as a whole must continue to draw attention to the urgent therapeutic needs of those with a rare disease. * MEPs Against Cancer MPE Report on Myeloma Patient Perspectives 43

43 The Innovative Medicine Initiative (IMI) has established that it would be useful to support an IMI topic on co-ordinating R&D and enrolling studies on rare and neglected diseases, but this is not yet set up 57. IMI aims to focus on defining strategic themes with maximum impact and game-changing ideas and areas where the maximum number of companies can join forces in co-ordinated research 58. Patients views on trials: Rigorous control of the conduct of trials has made it hard for patients views to be heard, despite ethics committees including a member who is a patient or representative of a patient organisation. Patient input can clearly be significantly increased both on the review of the legislation itself and on ensuring the relevance to patients of the measured outcomes of individual trials. Currently two EU-funded FP7 collaborative projects are of particular relevance: 56 PatientPartner (Identifying the needs for patients partnering in clinical research) which aims to involve patients organisations so that research can be better adjusted to the real needs of patients, and PREDICT (Increasing the participation of the elderly in clinical trials) investigates why the elderly are under-represented in clinical trials and what can be done to improve their participation. Let s hear the bad news too: In industry-sponsored research, negative trials outcomes have historically not always been published but this is now changing. Patient organisations and other researchers need to know about negative findings as well as positive, in order to acknowledge treatments that are not effective or have worse side-effects and to save wasteful duplication of non-productive investigations. The proposed clinical trials regulation will require results to be reported to the national authorities within a year of the trial s completion; a feature that deserves solid support from patient organisations. Furthermore, the website will soon publish all results (positive and negative). This is likely to happen in the second part of Use of biological resources: It is important that as well as using financial resources to the best possible outcome, patients who have contributed tissues for laboratory studies should be confident that their tissue is being employed in top-end research that should ultimately benefit patients. Patients priorities Patients do not always have the same view of what is needed in myeloma research as that held by researchers. Priorities for patients are that research should be patient-centred: ideally it should provide strategically relevant evidence from which patients can benefit directly. Patients are very keen to take part in clinical trials Many patients are interested in participating in clinical trials, as the treatments being evaluated may well help to control their myeloma better or improve their quality of life. They must be referred by a doctor, but many online websites give details of trials that are currently recruiting patients. Among these are the EU Clinical Trials Register, which gives access to the EudraCT database used by national medicine regulatory authorities to enter clinical trial data; and the US database. IMI is a joint undertaking between the European Commission and the European pharmaceutical industry association EFPIA, that sets a strategic research agenda for innovative medicines, with joint funding 44 MPE Report on Myeloma Patient Perspectives

44 Ideal priorities for clinical trials a patient perspective Identify practical alternatives to corticosteroids Identify optimal treatment for elderly, high-risk patients Find a solution for peripheral neuropathy a side-effect affecting up to 75% of patients treated with bortezomib and thalidomide Allow patient-friendly studies (regardless of whether they are industry- or investigator-initiated) to become the basis for drug authorisations, as these take patients needs into account Publish up-to-date information on trials Conduct psychosocial research alongside clinical trials The outcomes of research should inform clinical and practical decisions whether to offer patients new treatments, or treatments modified in some way that improves the prospect of remission or reduces one or more side-effects. It should be ethical, non-competitive, and prioritised. Contact between patient organisations and trials groups is essential to make sure that researchers share these priorities and many clinicians would welcome this input, as patients are the recipients of treatment and the bearers of side-effects. Some of the key priorities for patient organisations in relation to seeking more patient-centred research are: Identifying a practical alternative to corticosteroids: This relates particularly to dexamethasone; currently a major treatment component but with unpleasant side-effects including weight loss and muscle wasting or weight gain, bloating, irritability, personality changes, hyperactivity and insomnia. Identifying optimal treatments for elderly, high-risk patients: Older patients are typically less fit and less able to tolerate intensive chemotherapy treatment followed by stem cell transplantation. They are usually offered less invasive (and less successful) treatment. This group of patients is therefore in great need of more satisfactory alternative treatments. Finding a solution to peripheral neuropathy: A common, distressing symptom of myeloma is pain, tingling, and numbness in the hands and feet as a result of peripheral neuropathy. It can be apparent at myeloma diagnosis, but affects up to 75% of myeloma patients treated with bortezomib and thalidomide 59. Flexibility for off-label drug use in clinical trials: Patient organisations are best placed to investigate with the European Medicines Agency (EMA) the possibility of more flexibility for clinical trials requiring a combination of new drugs that will be compared with existing authorised products ( reference drug or comparator ). Normally, authorised medicines have to be used within their licensed authorisation for dosing and schedule. Since its marketing authorisation, small changes in the dose or schedule of the reference drug have often been discovered that allow less side-effects without reduced efficacy. and MPE Report on Myeloma Patient Perspectives 45

45 In a clinical trial, experimental regimes can be tested, also for the licensed drug but the study proposal needs to clearly explain the rationale for a different dose and/or schedule and what it means in terms of safety and efficacy for the patients participating in the clinical trial. At this stage of clinical trial development, interaction with patient organisations who can bring the real-word patient needs in the discussion might be very valuable. Publication of up-to-date information about trials: It is of utmost importance to patients that plans for trials and their outcomes are published. Information on trials in the 27*** EU member states is already published in the EU Clinical Trials register. As not every country in Europe is conducting relevant trials, publication of results, as will be required by the coming EU regulation, will ensure that myeloma patients and their healthcare team can be fully informed about current trials and their scientific and clinical findings. The European Medicines Agency is currently examining and consulting on the practical and policy issues involved before the data it holds can be made available in the most helpful form to serve both patients and public health authorities 60. Research that can lead to personalised care: This is a vital aspect, because patients vary substantially in their response to different treatments and even in their response to a single medication being given at different stages in their progress. For this reason, the genetic causes of myeloma are being investigated closely; notably by the Multiple Myeloma Genomics Initiative of the Multiple Myeloma Research Foundation that has led to the complete mapping of the myeloma genome 61 and the CoMMpass SM study that will follow 1,000 newly diagnosed patients to determine the molecular and genetic changes underpinning the evolution of the disease 62. Psychosocial research: Alongside clinical trials are qualitative studies of patients and carers emotional and psychological needs, and strategies to support them. Patient organisations are calling urgently for more activity in this area, as they have access to the personal experiences of those affected by myeloma. Here also is the opportunity to argue for dedicated training and raised awareness among healthcare professionals. Inviting myeloma patient groups to the table Patients and patient organisations can play a huge and multi-faceted role in both laboratory and clinical research. Evidence suggests that this resource is being under-utilised, possibly to the detriment of other stakeholders in research. Patients and patient organisations can influence and assist the research agenda in many ways, including: Promoting research and raising awareness: Access to trials appropriate for the individual will clearly vary in different countries, according to the availability of suitable centres and research clinicians. Here there is a clear liaison role for patient organisations, which are ideally placed to provide the patient s perspective to the researchers, and to inform both patients and researchers about the practical needs for and availability of trials. Access can depend on the patient s level of initiative in searching internet databases, or the involvement or lack of involvement of the specialist in trials, or simply the availability of a trial appropriate to the patient at the right time in a reasonably accessible place. *** 28 Member States from July 2013, when Croatia will become part of the EU 46 MPE Report on Myeloma Patient Perspectives

46 Advocating policy changes: Patients and their representatives have a valuable contribution to make to the mechanisms that authorise clinical research the ethical committees and the protocol developers and to product market authorisation. At the European level, patient representatives participate and have full voting rights in the work of the European Medicines Agency (EMA) and a number of its committees relevant to myeloma including the Committee for Orphan Medicinal Products, of which the vice-chair is a patient representative 63, the Committee for Advanced Therapies and the Pharmacovigilance Risk Assessment Committee. Patient representatives also contribute to EMA advisory groups in the context of promoting drug development, ensuring clear information to patients and working towards equal access to treatments at European and national levels. Rare disease patients are invited to contribute as experts on the development of products appropriate to their disease, e.g. in protocol assistance (development). However, this involvement of patient representatives within EMA does not touch on pricing and reimbursement, which are not within the EMA remit. At a broader level in the EU, the EMA has established its Patients and Consumers Working Party with members from a wide range of European patient organisations. A major example of the contribution of patient organisations in obtaining product authorisation is that of thalidomide and Revlimid (lenalidomide) for use in myeloma in Europe; however even after EMA authorisation, the conditions for access in individual countries vary significantly 64. At national level, permanent patient representation on national regulatory committees is very variable between the countries and non-existent in many. Here, as well as supporting the same European objectives, patients representatives would also address pricing and reimbursement for treatments. Adoption and implementation of research outcomes: A further area of invaluable contribution from patients is that of health technology assessments (HTAs), which are used in many European countries by healthcare authorities to review evidence and guide decisions on the value for money or cost-effectiveness of various treatments. HTA bodies review the evidence of scientific studies, so it is very important for this to be supplemented by information from patients and carers on their real experience of the treatments in practice. This impact can include not only whether symptoms were alleviated, but to what extent, at what cost in terms of side-effects and what benefit the treatment enabled, that was not possible without it 65. Summary Research is a crucial area of interest to myeloma patients; potentially promising great rewards for the future but fraught with regulation, high cost and lack of focus on the patient. The coming EU regulation on clinical trials promises to reduce the administrative burden on researchers, so hopefully will inspire more clinical trials to be conducted in Europe and enable more European patients to benefit. Its effects will, however, take years to be felt as it only comes into force in In the meantime, patient organisations have an important role to play in making known patients priorities, and their urgency, to both policymakers and those conducting and funding research in both the public sector and the pharmaceutical industry. MPE Report on Myeloma Patient Perspectives 47

47 Recommendations: Research For all stakeholders: Aim for greater collaboration between the different stakeholders involved in research in order to develop strategies that meet all their varying objectives and to reduce duplication Support and invest in collaborative research e.g. through joint projects, EU-funded collaborations between industry and academia and undertakings such as the Innovative Medicines Initiative Direct research towards initiatives that will make the greatest improvement to the lives of people living with myeloma For patient organisations: Highlight to government agencies the most promising outcomes from clinical trials, so that their findings on new therapies can rapidly be built into treatment guidelines Give positive support to the aims of the proposed EU regulation on clinical trials towards creating more equal access for patients to clinical trials throughout Europe and to encourage trials investigators to conduct their research in Europe once procedures have been made more uniform Take the opportunity presented by the new clinical trials regulation to call for more patient representation in the control of clinical trials and to emphasise that new drugs should truly address the needs of myeloma patients and not just the requirements for market authorisation Advocate urgently for more research on patients needs for psychosocial support and for dedicated training and raised awareness of healthcare professionals of the emotional needs of patients and carers For market authorisation authorities (European and national): Monitor and benchmark the quality of research studies in order to ensure that patients' needs are reflected in the outcome of investment For international research foundations: Continue, and where possible extend, their support for clinical research into alleviating and ultimately curing myeloma Continue and extend their interaction with patients in order to highlight the greatest priorities for future research funding For the pharmaceutical industry: Increase mechanisms for interaction with patient representatives in the concept and design of clinical trials Prioritise studies focused on patient needs Publish negative findings as well as positive, in order to acknowledge treatments that are not effective or have worse side-effects than existing treatments 48 MPE Report on Myeloma Patient Perspectives

48 5. An effective policy framework for treatment and care in myeloma care MPE Report on Myeloma Patient Perspectives 49

49 5. An effective policy framework for treatment and care of myeloma patients Although not responsible for health policies or for providing healthcare in the member states, the European Union does play an important role in encouraging measures to improve public health and to co-ordinate national efforts. EU influence is important because its measures to promote centres of expertise and European reference networks will have particular benefit for rare diseases such as myeloma, where patient numbers are so few that there is a need for concentration of cases in order to ensure that the units or centres dealing with myeloma have the appropriated expertise. A highly co-ordinated system of referral and coordination of care would also be needed in order to guarantee the accessibility of patients who live in more rural or remote areas, since they can experience difficulty in reaching expert medical attention. Also high on the EU public health agenda are the aims to stimulate national cancer plans and to co-ordinate registers and databases. Key points Rare diseases, including myeloma, have been a priority for action in the European Commission s health strategy for ; reinforced by measures to improve access to orphan drugs and incentives to promote research into rare diseases However, not all member states ensure full access to every orphan drug, regardless of authorisation by the European Medicines Agency Key aspects of the EU and national policies relating to myeloma: o Identify and foster Centres of Expertise and improve the diagnosis and care capacity in member states o Create European reference networks and facilitate the participation of National Centres of Expertise to ensure patients access to medical expertise, information and to improve diagnosis, care, training and research o Develop uniform national cancer plans o Create guidelines for myeloma care o Give timely and fair access to orphan drugs o Ensure transparent and regulated drug pricing o Employ health technology assessments o Maintain comprehensive registers and databases Patient groups need to act and make input to clinical guidelines to ensure the EU legislation is effectively implemented locally, in order to; o Secure fair access to medicines for patients, o Avoid duplication of processes o Give timely access to orphan drugs o Improve diagnosis and care management 50 MPE Report on Myeloma Patient Perspectives

50 The current policy landscape in Europe In Europe, national governments are responsible for defining their health policy and for organising and delivering health services and medical care. The European Union does, however, have the role of complementing national policies and encouraging co-operation between the member states in improving public health, preventing physical and mental illness and diseases and obviating sources of danger to physical and mental health 66. As such, it contributes both legislation and non-binding recommendations which are directly relevant to myeloma care. The EU has been active on rare diseases, including myeloma, since 1999, and they were identified as a priority for action in the European Commission s health strategy for Current EU policy, set out in the Commission s communication of 2008 and the Council recommendation of 2009, supports national policies including national action plans, and encourages co-operation between member states and better information exchange 68. Crucially, the action plan calls on member states to support centres of expertise (also called centres of reference or excellence at member state level) and European reference networks in order to improve universal access to high-quality care for rare diseases 68. The criteria and conditions to be fulfilled by ERNs and CoE are now being developed by the European Commission, in compliance with article 12 of the cross-border healthcare directive. This step is reinforced by measures to improve access to orphan drugs, and possible incentives to promote research into rare diseases and development of orphan drugs 68,69. However in practice, not all member states ensure full access to every orphan drug authorised for the market 70. The Council recommendation on rare diseases, a political commitment of member states, called for member states to develop national plans for rare diseases by 2013 at the latest; to contribute to information resources, to identify needs and priorities for research and support national participation, to support the creation of centres of expertise, to employ national expertise to contribute to European guidelines, training and sharing of best practices, and to encourage empowerment of patient organisations 71. The European Union Committee of Experts on Rare Diseases (EUCERD **** ) was set up in 2009 to support European Community actions in this area. The European Commission also funded the European Project for Rare Diseases National Plans Development (EUROPLAN ) between , and recently has funded in agreement with the member states a joint action on rare diseases ( ) which will take forward and complement the work carried out by EUROPLAN, giving support to national health authorities in their development and implementation of national plans for rare diseases. Orphan drugs are those intended for the diagnosis, prevention or treatment of a life-threatening or chronically debilitating condition affecting not more than 5 in 10,000 people, i.e. a rare disease Council recommendations call for a particular course of action but unlike directives or regulations, have no legal obligation **** PP 1.html MPE Report on Myeloma Patient Perspectives 51

51 Key aspects of European and national policy Centres of expertise: The idea of developing centres of expertise, raised in the EU s 2008 communication, was again reinforced by the European Parliament s 2010 resolution stressing that special action is to be taken for rare and less common cancers. The Directive on patients rights in cross-border healthcare specifically addresses the topic of European Reference Networks and Centres of Expertise in its article 12, providing a first legal basis for the implementation of networks and common criteria for the recognition of Centres of Expertise at EU level. The aim of the centres and networks is to share expertise with other centres across the EU and to establish networks of knowledge and care and herewith accelerate diagnosis and make expertise more widely available 72. These centres will comply with strict criteria and conditions (which are being developed by the European Commission at the moment) and offer services specialised, i.e. for single or a group of rare diseases. In some countries there are already similar systems of designation in place. However, although the criteria for designation are in line with the EUCERD recommendations 73, they do vary between countries 70. National centres of expertise in Europe (December 2011) CE designated in the context of a national RD plan/strategy CE designated outside of a national RD plan/strategy CE officially recognised to varying degrees but not designated CE by reputation only/self declared Countries with plans to designate centres with a national RD plan/strategy Source: 2012 Report on the state of the art of rare disease activities in Europe, of the European Union Committee of Experts on Rare Diseases MPE Report on Myeloma Patient Perspectives

52 European reference networks: In 2008, the European Parliament specifically called on the European Commission to use finance from the structural funds and the Seventh Research Framework Programme to set up and fund reference networks for rare and difficult-to-treat cancers, in order to pool resources and expertise and improve diagnosis and treatment 74. The Commission responded with its European Partnership for Action against Cancer for , to co-ordinate actions taken by the member states and other participants. This would be followed by a new joint action on cancer ( ) which will complement the work already done. The Commission s 2009 recommendation called on the member states to encourage the formation of reference networks to link the centres of expertise in rare diseases, and to improve access to diagnosis and quality healthcare. The directive on patients rights to crossborder healthcare 75 sets the objective that European reference networks can improve the access to diagnosis and the provision of high-quality healthcare to all patients who have conditions requiring a particular concentration of resources or expertise. These networks were designed to encourage the exchange and co-operation among professionals and between the centres of expertise. They are also focal points for medical training and research, and for dissemination and evaluation of information, especially for rare diseases. The directive gives the Commission s undertaking to develop the conditions and quality criteria for the reference networks 75. From the patient s viewpoint, the networks are a very valuable advance, as they enable them to benefit from the knowledge and expertise of medical researchers in other member states. As yet there are no designated reference networks directly relating to myeloma, but pilot evaluation has been made of networks in 11 other disease areas, identifying issues to be addressed for future networks 76. It is important that patient organisations are vigilant during the development, during , of the mechanism to set up the European reference networks. This is a major opportunity for patient organisations to influence their national governments and the European Commission to take into account patients needs, for example, in relation to research. The inclusion of research professionals should be decided by strict but neutral criteria. National cancer plans: National Cancer Plans, advocated in 2009 by the European Commission s communication on action against cancer 55, are public health initiatives intended to reduce cancer incidence and mortality and to improve the quality of life of cancer patients. To do this they use evidencebased actions for prevention, detection, treatment, palliative care and research 77. High among their objectives are to promote the development of care management guidelines and to emphasise the importance of early diagnosis. Some member states have not even begun work on national cancer plans and they are still under development in others. A 2009 study of national cancer plans in 31 European countries found only 19 functioning national plans (of which four were for the constituent countries of the UK) 78 and significant differences remained between them. Gaps were evident in many, in respect of governance, targets, timelines and financing 78. MPE Report on Myeloma Patient Perspectives 53

53 Access to drugs for rare diseases: Critical medicines are still not available. Drugs to treat rare diseases must be both available and affordable. In the EU, there are many examples of critical medicines not being available, for example in Romania, while in Poland access still depends on negotiation between the pharmaceutical industry and the reimbursement authority A call to establish common pricing and reimbursement decisions. A proposal was developed in 2009 by the European Organisation for Rare Diseases (EURORDIS), with industry and academic leaders to call on the European Commission and the European Medicines Agency to establish a working party for European collaboration toward common scientific assessment of the clinical added value of orphan drugs 79. The intention was to establish a common basis for national pricing and reimbursement decisions Three surveys were conducted by EURORDIS in , and the EU Pharmaceutical Forum concluded that equitable and timely access to approved drugs for rare diseases patients remains an issue and effective market access and utilisation vary strongly between and within member states 80. The European Commission mandated a study from Ernst & Young, which provided the basis for the 2012 recommendation of the EU Committee of Experts on Rare Diseases 80. The recommendation sets out a mechanism for information exchange between member states in order to help them to make informed decisions on access to orphan medicinal products and, most notably, to bridge the knowledge gap at the time of marketing authorisation 81 Is sharing the risk a viable answer? One alternative approach to financing orphan drugs is to share the risk. This has been used in the UK for providing bortezomib (Velcade ) to treat myeloma. The arrangement is that the National Health Service pays for the drug only when patients show a full or partial response to treatment after four cycles of treatment. If not, the manufacturer will refund the full cost or provide a replacement product. Such arrangements give access for the patient and minimise the cost to the healthcare system, but their effectiveness in improving access to new products has not yet been properly evaluated 82 Early approval for severe conditions with significant unmet need. The EMA approval process is very relevant to the availability of drugs for myeloma, with increased pressure for its mechanism of early approval in cases of severe conditions with significant unmet need 83. In addition to the normal comprehensive procedure, the EMA is able to grant early, conditional approval in cases where it is possible to demonstrate a positive benefit/risk balance based on preliminary evidence. This type of approval, renewable annually, carries the absolute obligation to provide the missing data towards a normal market authorisation 84. This is an area where patient organisations are best placed to advocate for wider use of conditional approval, both in specific cases and as a general principle Drugs pricing: Objective, non-discriminatory pricing for cross-border healthcare. Pricing for medication is negotiated between the national pricing and reimbursement authorities and the pharmaceutical industry. The cross-border healthcare directive requires that drug pricing information is given clearly and that the same fees as for domestic patients are charged to those from other member states. If there is no comparable price for domestic patients, the price should be calculated according to objective, nondiscriminatory criteria 54 MPE Report on Myeloma Patient Perspectives

54 A call for the cross-border healthcare directive to safeguard patients access to medicines. A great deal depends on the effective transposition and implementation of EU legislation within the member states, as drug pricing directives have to be transposed into national law. Access to medicines can be impeded for less affluent patients in countries where the patient is required to pay up-front, and be reimbursed later. Patient organisations have until October 2013 to call on their national governments to transpose the cross-border healthcare directive in a way that effectively safeguards the needs of patients Measures regulating the prices of medicinal products to be transparent. Also of great significance is the amendment proposed in March to the 1989 directive on transparency of measures regulating the prices of medicinal products. The original directive regulates the power of EU member states to set the pricing and reimbursement conditions for medicines, but had become seriously outdated. The proposed amending directive will replace the original, extend its pricing and reimbursement controls to cover health technology assessments (next paragraph) and reduce the time limit for pricing and reimbursement decisions to 60 days, which should improve patients access to new medicines Health technology assessment (HTA) Methodologies for HTAs to be shared across borders. The cross-border healthcare directive gives the European Commission s support for a voluntary network connecting national authorities or bodies responsible for health technology assessments designated by the member states (see section 4: Research). The network should avoid duplication and support collaboration between member states in developing and sharing methodologies for health technology assessment, including relative effectiveness assessment 75 Guidelines for myeloma treatment and care A need for uniform clinical guidelines. These are intended to guide decisions in diagnosis, management and treatment in specific therapeutic areas, based on the best available evidence and consensus. Difficulties can arise through differing approaches of guidelines from different sources. At present, standards vary because of the rarity of myeloma and consequent delay in diagnosis and because of differing pricing and reimbursement structures. European treatment guidelines and consensus statements have been published and are regularly updated, but the presence of too many can dilute their value 86,87 Myeloma Patients Europe to contribute to the development and application of a uniform European consensus on optimal care. This is a key aim of the group, so that myeloma patients can receive the same high level of care throughout Europe. The key limitation to this aim is the different national reimbursement decisions which may restrict the availability of some medications. The UK Myeloma Forum, which developed the key guidelines on diagnosis and management of myeloma and supportive care, is keen to work with the National Institute for Health and Clinical Excellence (NICE) to develop NICE guidelines on myeloma management. Such guidelines would be highly influential in the prospects of developing European guidelines MPE Report on Myeloma Patient Perspectives 55

55 Registers and databases Data is essential, but epidemiological data on individual rare cancers like myeloma are very few. The Orphanet database shows 28 myeloma registries in only 15 EU member states 88. Data on the epidemiology of myeloma is essential in order to examine its incidence across Europe, to reveal the discrepancies and to identify regions of better practice in order to share effective strategies 89. Orphanet and other databases also provide invaluable information on current clinical trials (see page 50). Policy solutions to lift the barriers to excellent myeloma care Clearly a great number of initiatives are already in place both nationally and at the European level, but patients are not receiving a uniformly high level of care. So what policy solutions can contribute to breaking the barriers to achieving excellence in myeloma treatment and care? Access to novel medicines While not questioning the sovereign right of national health authorities to manage their reimbursement policies, there is room for EU-level recommendation that variation in national reimbursement policies, which damages the treatment prospects of patients, is removed. The onus is also on the pharmaceutical industry: not to place medicines beyond the reach of health authorities on the grounds of price Access to optimal care Uniform guidelines for myeloma diagnosis, management, treatment and supportive care that were fully implemented across Europe would be a major contribution to raising standards and improving equity. National cancer plans are running or under development in most member states but show significant shortcomings in terms of governance. To be effective, they should not only set targets, but be followed by regular, independent assessment including evaluation of results and targets achieved or missed Centres of expertise and European reference networks are at an early stage of development and need effective co-ordination, evaluation and extension into the other areas including blood cancers; but they should eventually contribute to patients access to the highest level of treatment. Where it is not possible for patients to reach such centres because there are none in their own country, the reference networks should be fully employed to enable transfer of staff or at the least, electronic consultation and transfer of expertise. Also, good communication between centre of expertise and other local specialised and non-highly specialised healthcare providers (follow up, palliative care, etc.) is essential for patients that are not receiving highly specialised care at that moment but need specific attention (weak immune system, etc.) Access to cross-border healthcare Patients prefer to be treated in their country of residence, but when this is not possible or it is taking too long to get the diagnosis or treatment, they have the right to cross-border healthcare (as provided by the 2004 EU regulation on the co-ordination of social security systems 90 and the cross-border care directive). However, even under these improved conditions of access, patients who go to other countries for treatment may still bear the responsibility for finding information on potential treatments, demonstrating to insurers that the treatment has been carried out and submitting the correct documentation 91.The European Commission estimates that the cost of total cross-border healthcare is about 1% of EU public healthcare spending 92 a small proportion but vital spending for rare diseases 56 MPE Report on Myeloma Patient Perspectives

56 The directive on cross-border healthcare provides that national governments may choose which reimbursement mechanism is to be used for care provided to patients from other member states, and include it in their legislation before Patient organisations should call on their national governments during this time of preparation of national laws to implement the directive to select a direct payment from the member state of residence of the patient, to the member state of treatment. The alternative is for the patient to have to pay upfront, and then reclaim the amount from their own member state. Access to trials is not currently available in every European country, because of the rarity of myeloma and the availability of research hospitals. The recent proposal for a Regulation on clinical trials on medicinal products for human use (which, if adopted, will repeal the currently applicable Directive 2001/20/EC on clinical trials) would work towards further harmonisation in the area of clinical trials, facilitating the process of carrying out clinical trials in several EU member states at the same time and therefore improving patients ability to participate in trials in other countries. It does not, however, remove the related practical difficulties of travel, expense and family/carer disruption Early diagnosis More training for doctors is the obvious suggestion to help increase awareness of a possible myeloma diagnosis. However, because it is such a rare occurrence in a lifetime of medical practice, the best option must be continuing medical education and regular reminders of the devastating consequences of a missed diagnosis, plus research into diagnostics Input of patients priorities into policy-making Although patient organisations are now able to participate in the working of many ethical and regulatory committees, this input still needs to spread further in all European countries. Input of patients views and priorities has met with some resistance, but there is plentiful evidence that they can add materially to the effectiveness of health authorities decisions. The UK government s commitment to ensuring that patients and the public have a voice in how cancer services develop was given in its 2011 strategy for improving outcomes in cancer 93 ACCESS is the key for patients Optimal care depends on patients access to: Novel medicines Effective care plans Cross-border healthcare Expertise Uniform guidelines Clinical trials Early diagnosis Opportunity to input patients priorities into policy making. MPE Report on Myeloma Patient Perspectives 57

57 Recommendations: Policy For national healthcare policymakers: Develop a clear national cancer plan and within it, clear objectives for diagnosis, treatment and management of myeloma; while taking patients quality of life into full account as an essential outcome If a national plan is already in place, bring it into full implementation and ensure effective provision for governance, budget, targets, timelines and review Include quality of life indicators in market authorisation dossiers 82 Re-examine national criteria for pricing and reimbursement of orphan drugs to ensure that access to them is not restricted for patients on the basis of price Work to implement EU recommendations on centres of expertise and European reference networks, especially as they develop in the field of blood cancers Work towards uniform treatment guidelines to encourage more uniform access to innovative treatments, a uniform level of reimbursement and a high level of care throughout Europe Establish or expand patient registries for cancer and specifically myeloma, to gather evidence on health-related quality of life in addition to basic epidemiological data For patient organisations: Work to develop knowledge of national and European policies and the expertise available for interaction with national policymakers Monitor the establishment of European reference networks and advocate for full account to be take of patients needs Monitor the transposition by national governments of the EU cross-border healthcare directive to ensure optimal access to treatments, and call on governments to select direct repayment in national mechanisms rather than reimbursement of patient expenditure Advocate for representation within the national health policy-making bodies, within committees contributing to authorisation of clinical trials, reimbursement decisions and health technology assessments Advocate for a uniform patient pathway (providing for personalised options), with reimbursement of medications at the same level throughout Europe Advocate for a faster drug authorisation process, or a wider access to drugs on the basis of conditional approval or approval under exceptional circumstances, i.e. before full authorisation Advocate for access to clinical trials being conducted in other countries, as this can offer access to novel drugs or combinations during the time between pivotal studies and market authorisation 58 MPE Report on Myeloma Patient Perspectives

58 6. The power of patient advocacy in myeloma: making it happen MPE Report on Myeloma Patient Perspectives 59

59 6. The power of patient advocacy in myeloma: making it happen Patient organisations are now a well-established and recognised partner with all of the professional and representative groups concerned with healthcare. They have the knowledge and commitment to present the patient s views and to press for attention and improvement where it is needed. Across Europe are many examples of their achievements; but also many other opportunities where greater successes are possible, through advocacy directed towards opinion-leaders in healthcare or politics, or through information and support to patients and their carers. Probably the greatest challenges to patient organisations are those of providing a professional service through a volunteer workforce, with limited finance, and of maintaining independence from other stakeholders. Key points Patient advocacy exists to: o Promote excellence in myeloma treatment and care o Improve treatment and quality of life for myeloma patients o Provide information and practical support or patients and their carers o Contribute towards, and improve access to research and new treatments o Contribute patients views and experiences in the making of healthcare policy Patient organisations depend on patients, carers or other supporters for their activities and operation Patient groups have very substantial and far reaching effects Alliances with medical professional organisations give access to their skills and knowledge, enabling effective interaction with healthcare regulators, payers, politicians and other interested groups Raising awareness of myeloma among general practitioners and orthopaedic specialists for a quicker diagnosis and referral Advocacy goals The aim of advocacy in myeloma is to improve, in every way possible, the treatment prospects and overall quality of life for those affected by the condition. This can be through providing information or practical support for patients, contributing and increasing access to research into new treatments, or representing patients and advocating for their views and experiences to be taken into account in healthcare policies. In Europe this is being achieved through the efforts of national and regional patient organisations and those of individual patients, healthcare professionals and corporate supporters. Myeloma Patients Europe (MPE) is an umbrella network of these patient organisations and supporters, formed in 2011 by the merger of the former associations, European Myeloma Platform and Myeloma Euronet. 60 MPE Report on Myeloma Patient Perspectives

60 The aims of Myeloma Patients Europe Collaborating on projects to the benefit of the myeloma community* Exchanging information and best practice Developing existing patient groups, and encouraging and facilitating the setting up of new groups Helping to shape appropriate health-related policies and initiatives on a European and national level Ensuring patients across Europe receive timely access to new treatment Stimulating and promoting patient-centred research and clinical trials Developing a strong evidence base for the needs and wants of patients, and their role in research Providing information, educational and outreach programmes to member groups Most of the work of individual patient organisations is carried out by patients, carers or other supporters, who are volunteers and may be limited by illness or have other commitments. For this reason, it is important to develop alliances with other organisations, which give MPE and many individual patient organisations access to the skills and knowledge of healthcare professionals and other experts. This enables effective and professional interaction with all the many groups and organisations that have interests in and influence over what actually is offered to myeloma patients the healthcare regulators and reimbursement authorities, politicians, the pharmaceutical industry, the media and through them, the public. Even within each patient organisation, though, ideally the structure, communication and responsibilities should be clearly designated in order to achieve effective activities 94. Advocacy and participation in professional regulatory and ethics committees demand a thorough understanding of both the scientific and medical aspects of the subject, and the ability to convey the patients perspectives effectively. What have myeloma patient organisations achieved to date? A 2012 survey of senior healthcare professionals and pharmaceutical industry executives found that European and national patient groups as a whole were well regarded in their country 95. Half of the healthcare professionals and 42% of the industry executives believed that their own medical specialty had been prioritised by their government as a result of patient organisation campaigns 95. The same survey revealed that these two groups also regularly used the websites, online forums and social media sites of patient organisations as a source of information 95. In myeloma, one of the most significant single achievements of the patient movement has been in work by several patient organisations in Europe in collaboration with thalidomide victims associations. In the US, thalidomide (Thalomid ) is distributed under a strict RMP (Risk Management Plan) and PPP (Pregnancy Prevention Programme), called STEPS. However, the conditions of the STEPS programme were not appropriate to the EU context and European myeloma patients. e.g. as a partner in research projects with European Myeloma Network, and with EMA and thalidomide victim associations concerning risk management plans and pregnancy prevention programmes for thalidomide, lenalidomide and soon pomalidomide MPE Report on Myeloma Patient Perspectives 61

61 The collaborating associations signed a common position paper, reflecting the agreement of all involved on the need for an effective RMP and PPP for the use of thalidomide (European brand name: Thalidomide Celgene ) for myeloma treatment in Europe, differing in key respects from the US STEPS programme 96. In the following years, several meetings with the patient organisations, the victims associations and the regulators took place at the agency, during which input on the EU core RMP and PPP for Thalidomide Celgene and Revlimid, a thalidomide analogue, was given. The result was that an EU core RMP and PPP were adopted by EMA and implemented with the marketing authorisation of Revlimid (2007) and Thalidomide Celgene (2008). Since then, all EU countries where Revlimid and Thalidomide Celgene are marketed follow the core European version of the RMP and PPP 64. Patient organisations also have had an important impact on the content and design of clinical trials. Myeloma Patient Groups Achievements: Well regarded, with many experts using websites, online forums and social media sites of patient groups as a source of information Increased overall survival of myeloma patients over the last 10 years by pushing through the initiation of a Risk Management Plan (RMP) and Pregnancy Prevention Plan (PPP) in Europe, enabling the authorisation of Revlimid and Thalidomide Celgene An important influence on the content and design of clinical trials Challenges: Economic constraints Increasing workload Maintaining independence from sponsors/supporters Ensuring a complete and effective service, while relying on patients and volunteers as a workforce with support from healthcare professionals 62 MPE Report on Myeloma Patient Perspectives

62 Patient organisations successes some more examples UK: The TAKE 2 Campaign The Myeloma Diagnosis Pathway is a simple but effective decision-making tool for GPs, developed by Myeloma UK. It is designed to reduce delays in the diagnosis of myeloma by outlining its signs and symptoms and the investigations to carry out if GPs suspect someone has myeloma. It has been provided to over 7,000 GPs across the UK, through asking patients, family and friends to take two copies of the Pathway to their GP and encourage two friends to do the same. A film about it was also launched for wider distribution. GPs have reported back on how useful they found it. Dr Lynn Jones, a London GP, commented: I was really impressed by how useful and informative the Myeloma Diagnosis Pathway is. I am now using it in my practice and I encourage my colleagues to do so too. Myeloma UK is now working to have it introduced into established GP education and in-house training programmes throughout the UK. Slovakia: Multimedia education course The Slovak Myeloma Society is a network of myeloma patient groups across Slovakia, whose aim is to raise the quality of patients lives, to help them feel they are not alone with their problems, and to work together with family members and relatives. The Society s Patients Club was set up to provide information on the diagnosis, treatment and care of people living with multiple myeloma, and support for their families. A major project has been to publish a simple CD-based course about myeloma and its treatment for patients, nurses and anyone affected by myeloma; in Slovak (2007) and English (2011). The course uses colourful slides and animations to explain the facts in a highly visual and accessible way. It has been presented in local and national patients meetings in Slovakia, and also at European-level patient organisation meetings and patients days in London, Vienna, Brussels and Zurich. Germany: Setting up new patient support groups The APMM network of regional myeloma groups in Germany (Arbeitsgemeinschaft Plasmozytom, Multiples Myelom) supports the establishment of new myeloma self-help groups in regions that do not have one already. It offers help with organising and financing for a Patients Day. These are always organised in co-operation with the haematology department of the regional Universitätsklinik. Setting up these myeloma groups is welcomed and greatly respected by the doctors, and generates their support for the group in the future. In addition, the APMM website is kept up to date at all times with the most recent news about myeloma. Spain: Multiple initiatives for patient support AEAL is the Spanish Group for Lymphoma, Myeloma and Leukaemia patients (AEAL), In May 2012, it created a subgroup, Mieloma España, at the request of the large number of myeloma patients and their relatives seeking support. In the short time since then, Mieloma España has already continued the work for myeloma patients already under way in the parent organisation AEAL. Each year since 2006, AEAL has made up to ten visits to different Spanish towns to raise awareness of myeloma, and participated in the annual Spanish Cancer Patient Group congress in Madrid. Online seminars have been held since 2010, to give myeloma patients free interactive access to presentations from haematologists; all of which are recorded and available from the AEAL, GEPAC (Grupo Español de Pacientes con Cáncer) and Mieloma España websites. AEAL also developed an online elearning facility called e-cancer Campus, offering a myeloma education course for patients and carers. Psychological and social support is also available to patients from AEAL, and as a more practical means of support, the AEAL Apoya project has provided orthopaedic beds for myeloma patients with bone problems. MPE Report on Myeloma Patient Perspectives 63

63 Challenges faced by myeloma patient organisations Financial resources: The greatest challenge must be maintaining adequate finances at a time of economic constraint; offering a service at a time although operating through limited donations or fund-raising. Healthcare systems are experiencing greater pressure than ever before, while patients have increased their knowledge and desire to be actively involved in their own care, and are increasingly turning to patients associations and voluntary groups for information and reassurance. The net result for patient organisations is an increasing workload and a limited or decreasing budget. Maintaining independence: Secondly, the pharmaceutical industry is a valuable supporter of some initiatives of patient organisations; however patient representatives must maintain their independence and ensure completely transparent arrangements with industry sponsors. This principle is safeguarded by the code of practice for relationships between the industry and patient organisations adopted by the European Federation of Pharmaceutical Industries and Associations (EFPIA) in 2007 and updated in Member associations of EFPIA (the national pharmaceutical industry associations) were required to adopt the code into their own national codes of practice by December The EFPIA code of practice for relationships with patient organisations 81 The independence of patient organisations, in terms of their political judgement, policies and activities, shall be assured All partnerships between patient organisations and the pharmaceutical industry shall be based on mutual respect, with the views and decisions of each partner having equal value The pharmaceutical industry shall not request, nor shall patient organisations undertake, the promotion of a particular prescription-only medicine The objectives and scope of any partnership shall be transparent. Financial and non-financial support provided by the pharmaceutical industry shall always be clearly acknowledged The pharmaceutical industry welcomes broad funding of patient organisations from multiple sources 64 MPE Report on Myeloma Patient Perspectives

64 Professionalism: The third challenge is the need to ensure professionalism. Many patient organisations are staffed by volunteers, who may also be patients, and are presented with an extremely demanding prospect. Their agenda is likely to involve interaction and negotiation with medical experts; requiring a high level of knowledge and understanding of a very complex disease. Some organisations would have difficulty in providing individuals able to meet these requirements and have two options: to enlist the support of medical professional organisations or to engage in staff training programmes again, this may be a challenge for funding. Driving change from West to East The ultimate aim of the myeloma patient movement in Europe must be to promote excellence in myeloma care, throughout all of its countries and regions. This report has shown many discrepancies between the best available care and what is available in practice, particularly in the newer Eastern EU member states and also in rural regions, where patients need to travel long distances for specialist care. The European Union is committed to reducing disparities between its regions, as part of its drive to strengthening the economic and social conditions across all the member states. It acknowledges that health is a vital part of those efforts, as a healthier population contributes to economic and sustainable growth and makes less demand on healthcare systems 99. Between 2007 and 2013 the EU has also committed over 5 billion to improving health infrastructure through the European Regional Development Fund (ERDF) and the European Social Fund (ESF). Among current projects relevant to myeloma are almost 78 million for the construction of the Centre of Preclinical Research and Technology (CePT) in Warsaw, Poland, which will focus on fundamental research, new diagnostic methods and new therapeutic approaches; and almost 67 million for upgrading the North Estonia Medical Centre, Tallinn, to offer advanced treatment for oncology and cardiac patients 100,101. Patient movement input to the European Union At European level, patients associations for myeloma (like those for cancer and rare diseases) need to be in active contact with the European Commission s directorates concerned with health and with research; monitoring policy development and making input on patients priority issues. Also, importantly they should be in contact with relevant members, groups and committees of the European Parliament, who can draw the attention of politicians and policymakers to the critical issues for myeloma in Europe by asking formal questions of the Council and Commission and by arranging discussion forums. Within the Parliament, MEPs have already adopted a declaration calling for improved co-ordination of cancer research 102. Formerly meeting within the cross-party group MEPs against Cancer (MAC), interested MEPs now participate in the Forum Against Cancer Europe (FACE) initiative of the European Cancer Patient Coalition (ECPC). FACE is well aware of the issues relating to rare cancers, but input specific to myeloma would be valuable 103. MPE Report on Myeloma Patient Perspectives 65

65 What can patient advocacy do? Effective advocacy. This can have very substantial and far-reaching effects. As shown in the examples given above, it can contribute to making myeloma a priority on national health agendas, and support research programmes Provide expert patient advocates, able to present the needs of myeloma patients to all stakeholders in myeloma healthcare professionals or administrators on a local level, or regional or national policymakers, reimbursement officers, ethics or regulatory committee experts, or industry or academic researchers, or the media Identify and engage with the key opinion leaders who are receptive to information from the patient organisation and in a position to improve myeloma care Provide information, training and personal experience of myeloma. The areas patient representatives are able to address will depend on the circumstances, culture and critical issues in their own country. These may be the availability of trials, access to specialists, reimbursement levels or any of the many diverse aspects of living with myeloma. Clearly in some countries the patient-doctor and patient-health authority relationships are more open to input from a patient representative than in others Provide education for all patient advocates. This is a central aim for MPE, which is now offering national patient organisations training in specialist aspects. Not all patient advocates will be able to present the most complex aspects e.g. the health economic implications to health authorities. The ideal would be to train and encourage some patient advocates to address e.g. clinical trials and research issues, while others focus on regulatory and reimbursement issues e.g. making input to health technology assessments; while any could speak for the organisation on living with myeloma Active and structured collaboration with professional medical associations and scientific societies. These can add substantially to the resources of patient organisations. Within these organisations, interaction with individuals, committees and task forces can elicit expert advice and support, for example in negotiations with regulators and policymakers. Taking part in joint initiatives with professional organisations will result in increased recognition of patients perspectives Share resources from other myeloma associations. Not every patient organisation has the financial or personnel resources to do everything that it might wish. However, it is always possible to share resources; either in person or by electronic means. Some of the associations have already developed large and comprehensive information resources which could be made available to other associations. The same principle of working through others can be applied where an organisation is unable to gain membership of a committee: it may be possible to reach an understanding with and make indirect input through an existing member Share information and advice. A wide range of other tools can be used by patient organisations to raise general awareness or to advocate on particular issues, either directly or by informing key opinion leaders. Again, some of the member associations within MPE have well-developed examples that can be shared or adapted, and may well be able to share information or advice. They include: Websites, with news, expert articles, discussion forums Social media sites Advocacy events, e.g. roundtable discussions with experts and selected media 66 MPE Report on Myeloma Patient Perspectives

66 Social events with a local focus and media presence Input to medical or social care conferences, e.g. presentations, posters Publications journal or magazine articles Develop or share existing programmes for informing healthcare professionals about myeloma. This is an extremely productive option for patient organisations particularly in the areas of diagnosis, novel treatments, and psychosocial support. Programmes can be either in group training or individual online resources such as is offered in the UK by Myeloma Academy *****. At present the resource is tailored for haematologists and nurses, and will soon also cover GPs and other healthcare professionals. It offers best practice guidance, a searchable database on drugs in development, a clinical trials tracker and detailed guidelines and key publications. Raising funds. As voluntary organisations dedicated to improving the lives of people with myeloma, their patient organisations depend for their funding on the work of volunteers and the generosity of the public. As well as practical fund-raising activities, patient organisations are well placed to raise awareness of their financial needs for actions and campaigns, through their contact with other influential organisations, government bodies and funding sources ***** MPE Report on Myeloma Patient Perspectives 67

67 Recommendations: Patient advocacy For national patient organisations: Identify, make contact with and inform key opinion leaders who are in a position and have the influence to make a difference to the services available to people with myeloma. These are among all stakeholders in myeloma: healthcare professionals, administrators on a local level, regional or national policymakers, reimbursement officers, ethics or regulatory committee experts, industry or academic researchers, media Collaborate actively and in a structured way with professional medical associations and scientific societies to obtain their expert advice and support in negotiations with regulators and policymakers Develop the knowledge and abilities of team members within the patient organisation, drawing on information resources from other national organisations and taking up opportunities for training in effective advocacy and in business management Encourage and train individual patients who have the aptitude to become expert patient advocates Seek opportunities for patient representatives to participate in key policy-making and ethics committees and in the design of clinical trials Seek opportunities to raise awareness of myeloma among healthcare professionals and the public, e.g. through information workshops Explore the information and communication resources of other national organisations and share ideas that could be adapted For Myeloma Patients Europe: Develop access to education in advocacy on specialist aspects of myeloma for the staff of patient organisations Develop a Europe-wide database of information resources and successful advocacy initiatives, to be available to the patient organisations Promote the training resources of the Myeloma Academy to healthcare professionals in other European countries Continue interaction and engagement on key issues with all relevant EU institutions the Commission s Directorate General for Health and Consumer Affairs, the Health Working Group of the European Parliament s Committee on Environment, Public Health and Food Safety, and individual Members of the European Parliament 68 MPE Report on Myeloma Patient Perspectives

68 7. Achieving excellence in myeloma care case studies MPE Report on Myeloma Patient Perspectives 69

69 Achieving excellence in myeloma care case studies Germany: Keeping informed about clinical trials In the Universitätsklinikum Heidelberg, the Physician and patient hand in hand project is run jointly with the regional myeloma patient organisation. In daily practice, this means that the leader of the self-help group comes to the patient, whenever and wherever needed; called by the clinical personnel responsible, usually the doctor. Through this practice, the group leader is accompanying the patient step by step, explaining to him/her exactly what is going on. In this way, it is easier for the patient to accept the treatments and actions which are necessary, and it also encourages them to participate in the clinical trials offered. The Netherlands: Finding out what patients really need The Netherlands Myeloma and Waldenström association CMWP * provides information for both patients and carers including a regularly updated patients' handbook, support groups, newsletters and contact persons. At the CMWP annual symposium, speakers present the latest developments in medical treatment as well as emotional aspects. Working with researchers at Maastricht University, it is currently developing a survey of CMWP members, followed by focus group discussions, to define what aspects of myeloma care in the Netherlands they believe to be most important in future research, and what could be improved. The results will be analysed together with the findings from a literature survey, and the report will present a list of priorities that can be used to inform future clinical, education or information initiatives of the association, especially in future research. UK: The Myeloma Academy and the Myeloma Nurse Programme The Myeloma Academy is an online resource designed to meet the educational needs of healthcare professionals involved in the treatment and care of myeloma patients. It contains designated educational materials for both hospital doctors and nurses, including best practice guides, position papers, tutorials and challenging cases. The Myeloma Academy is currently accessed by over 300 healthcare professionals across the UK, including nurses, consultant haematologists and clinical scientists. Within the Academy's resources, the Nurse Best Practice Guides aim to enhance nurse knowledge, inform nursing practice and support nurses to deliver the highest quality of treatment and care to myeloma patients and their families. The Guides have recently been accredited by the Royal College of Nursing (RCN). The Myeloma Nurse Programme is a network of Myeloma Nurse Champions in UK myeloma centres, with access to resources for role development, education of colleagues, implementation of best practice and developing local patient services. Further information is on: 70 MPE Report on Myeloma Patient Perspectives

70 Acknowledgements MPE Writing Group: Dr Faith Davies, member of the Faculty at the Institute of Cancer Research (ICR), London and Consultant Haematologist at The Royal Marsden, London. Greetje Goossens, Myeloma Patients Europe Peter Lens, Myeloma Patients Europe Professor Heinz Ludwig, Head of the Department of Medicine and Medical Oncology, and Director of the Myeloma Reference Centre at the Wilhelminen Hospital in Vienna, Austria. Ananda Plate, Myeloma Patients Europe Lia Van Ginneken-Noordman, (Contactgroep Myeloom en Waldenström Patiënten (CMWP)) and For their valuable input: Wioletta Niznik (Weber Shandwick) Jude Leitch (Myeloma UK) For their stories of living with myeloma: Johan Creemers, Belgium Judy Dewinter, UK Greetje Goossens, Belgium Christa Kolbe-Geipert, Germany Mika Peltovaara, Finland Stewart McRobert, UK For examples and best practices: Alfonso Aguaron, Spain Miroslav Hrianka, Slovakia Christa Kolbe-Geipert, Germany Kate Morgan, UK Lia Van Ginneken-Noordman, The Netherlands Dr Tiny Van Merode, The Netherlands Report writer: Dr Vivienne Kendall, UK Sponsors: We are very grateful for the generous support of the following groups and organisations: Anonymus CPMW MPE Report on Myeloma Patient Perspectives 71