Real World Evidence for the Canadian Market

Transcription

1 WHITE PAPER REAL WORLD EVIDENCE August 2013 Real World Evidence for the Canadian Market

2 WHITE PAPER The Business of Pharmaceutical Marketing Real World Evidence for the Canadian Pharmaceutical Market The concept of Real World Evidence (RWE) has traditionally been defined as the development of evidence using additional data beyond evidence from randomized controlled trials (RCTs). The term arose in the pharma-epidemiology community, highlighting the contrast in the value of evidence developed from real-life clinical practice to that developed from RCTs. The goal is not to replace RCTs, which are considered the gold standard of evidence, but to complement them. Such an approach would be considered normal in many industries. Any consumer purchasing an automobile would consider both factory-reported performance and that reported by fellow consumers driving cars in real life. Such approaches have been the norm in health care for some time, too, although they would often have been considered as observational research or real-life clinical practice. So why has RWE become such a focus of attention in recent years? The goal is not to replace RCTs, which are considered the gold standard of evidence, but to complement them. Three factors explain the adoption of the term Real World Evidence. 1. First, there has been a rapid rise globally in the capture of health care data in routine electronic format, which has fundamentally changed the manner, cost and participants who generate evidence. However, this evolution has not been uniform. For example, Canada has been behind the global curve when it comes to capturing electronic health data partly because of the slow uptake of physician EMRs and the highly fragmented nature of the health care system. 2. Second, the ability to interpret RWE and apply it to key decision-making has accelerated, with high-profile examples of impact proliferating across health systems. 3. Finally, there has been recognition that RWE has broader applications than research, and the term RWE is often interchanged with Real World Data (RWD). These broader applications go beyond the notion of public evidence, but apply the same techniques and data to enable internal business decision-making in pharma and by payers. Examples include designing trials, patient pathways and patient profiles or structuring the relationship between key players (e.g. pay-for-performance agreements between payers and providers). Randomized controlled trials remain the gold standard for demonstrating product safety and efficacy to secure market access. However, the inherent limitations of their data small sample size, a controlled environment and focus on short-term outcomes meant payer and regulator negotiations were primarily focused on qualitative documentation of value. Quantification was extrapolated mainly by using health economic modelling. Evidence requirements have shifted radically and RWE creates new challenges and opportunities for companies to succeed in this new environment. These include: Increasing availability of and demand for reliable and robust data Changing the mix of data, with RWE used to complement RCT data Shifting ownership of data to third parties, creating data asymmetry Expanding assessments of safety, value and effectiveness based on RWE over the full life cycle of a drug product Evidence requirements have shifted radically and RWE creates new challenges and opportunities for companies to succeed in this new environment. 367

3 WHITE PAPER 2 These developments will significantly change the scope and relevance of outcomes research, with new paradigms and a major impact on value creation in the real world. Technologies are now transforming the value of data by enabling health care stakeholders to engage, make connections and draw inferences in ways that were previously not possible. In order to extract the value they need from real-world data, organizations must consider collection, aggregation, integration and presentation of the data. The past few years have seen a lot of innovation in RWE spanning data, analytics and technology, often enabled by partnerships between various stakeholders. These innovations are creating new opportunities for researchers to use real-world information with payers and regulators. For example: Encryption methodologies allow for de-identification, blending and linking data across various data sets, illustrating the full patient journey. Data marts integrate RCT with other data and allow companies to answer the same questions faster, for less money and answer new questions more easily. Software and data platforms enable access to data to both researchers and decision-makers in a more efficient manner. These developments will significantly change the scope and relevance of outcomes research, with new paradigms and a major impact on value creation and demonstration in the real world. Real World Evidence can be used to help support arguments from RCTs throughout the market access process, as shown in Figure 1. Figure 1 Where RWE Can Improve Access NOC/Price CDR/HTA Evaluation for listing Promotion PAAB Health Canada /PMPRB Does the drug do more good than harm in a defined group of patients? Price? CADTH/pCODR What are the health and value consequences associated with this drug relative to other interventions? F/P/Ts Pan-Canadian Purchasing Alliance What are the cost consequences and which patients are going to benefit most? Prescriber How does the drug perform relative to other interventions in this patient? AE alerts Risk/Benefit/ Price benefits Outcomes/ Value Superiority/$$ Program tracking Source: IMS Brogan RWE Team 368

4 WHITE PAPER 3 Evidence of Change PMPRB According to the Patented Medicine Prices Review Board, of 97 new drug products reviewed in 2011, 24 drug products were classified as Moderate Improvement. Of these 24 drug products, 11 (representing six medicines) were classified as Moderate Improvement based on primary factors and 13 (representing eight medicines) were classified that way based on secondary factors. The moderate level of therapeutic improvement is therefore being used and secondary factors are being applied. The types of evidence used have included randomized open label studies, observational studies, cohort studies, cross-sectional surveys, case control studies, guidance documents, expert opinion and expert opinion reviews. The secondary factors highlighted now as additional points for reviewing the pricing of products are: Route of administration Patient convenience Compliance improvements leading to improved therapeutic efficacy Caregiver convenience Time required to achieve the optimal therapeutic effect Duration of usual treatment course Success rate Percentage of affected population treated effectively Disability avoidance/savings Many of these factors are not available from clinical trials and will rely on RWE data both in Canada and in other countries to deliver the required evidence. CADTH In the summer of 2012, the Canadian Agency for Drugs and Technologies in Health published the Quality Assessment Tools Project Report July It reviewed and set standards for the way in which the body of evidence to support a health technology assessment is handled. Additionally, in a 2009 CADTH HTA report 1 the authors commented: Despite the apparent utility and the almost pervasive presence of administrative data, HTA analysts do not always have access to these data. Indeed, analysts have not made use of the secondary analysis of data from administrative databases in Canada. The lack of use may be due to the difficulties in obtaining the data and the analysts lack of familiarity with the intricacies of the data. A wider use of administrative data would enhance the relevance of HTAs to decision-makers who need to plan resource use. Many of these factors are not available from clinical trials and will rely on RWE data both in Canada and in other countries to deliver the required evidence. 1 Canadian Agency for Drugs and Technologies in Health. Using Canadian Administrative Databases to Derive Economic Data for Health Technology Assessments

5 WHITE PAPER 4 When studying the available administrative data, the linkage between visits, patients, prescriptions, lab results, time off work and patients vital signs are not typically available. Usually, the HTA then defers to an RCT linked with a budget impact analysis and a literature search. The evolution of RWE from EMRs and other non-claims data may enable CADTH to make decisions with enhanced insights. For example, the UK s Medicines and Healthcare products Regulatory Agency and England s National Institute for Health and Care Excellence use insights from CPRD (Clinical Practice Research Datalink UK) and IMS Health Disease Analyzer EMR databases. Pan-Canadian Purchasing Alliance The pan-canadian Purchasing Alliance is gaining momentum even though most activity is happening behind the scenes and is not for public disclosure. In the meantime, Pradaxa and Xarelto have been added to the PEI drug formulary and were two of the first drugs to be reviewed by the pan-canadian Purchasing Alliance, according to a statement 1 by PEI s Minister of Health and Wellness, Doug Currie. There is no doubt that demonstrating the value of medicine will be key in gaining the best price, early intervention and successful listing agreements. There appears to be uncertainty about the final methodology that will be used in reviewing products for listing. It is anticipated, however, that RWE data will be considered as part of a submission when it supports the demonstration of the value of a medicine. The guidelines laid out for Canadian BIAs specifically exclude nondrug-related costs, such as medical procedures, ER visits, physician visits and diagnostic procedures. Federal, Provincial and Territorial Drug Plans One of the pivotal documents used by payers to decide on listing a drug product is the budget impact analysis (BIA). The guidelines laid out for Canadian BIAs specifically exclude non-drug-related costs, such as medical procedures (e.g. surgeries), emergency room visits, physician visits, diagnostic procedures and hospitalizations. The guidance PMPRB provides to F/P/T plans for selecting product listing criteria encourages decision-makers to consider the greater financial impact of a new drug on the health care system. Signs of a more holistic approach to cost drivers within the health system are emerging. Achieving success will require concerted effort by the pharmaceutical industry in collaboration with provincial budget holders to create a new landscape where, for example, a new oral therapy can reduce costs of infusion clinics. PAAB-Approved Promotional Claims A January 2013 report 2 from the Pharmaceutical Advertising Advisory Board included the following statement: Claims based on observational evidence can provide additional information to aid HCPs [health care providers] in making appropriate therapeutic choices that may not be captured in claims based solely on experimental evidence, such as randomized trials. Observational research can reliably answer clinically relevant questions in a complementary way. It can also provide important information for clinical decisions in an easier fashion than experimental research. Some important information for clinical decision-making cannot be reliably answered with experimental studies Pharmaceutical Advertising Advisory Board. Guidance Document for Claims based on Non-Experimental (Observational) Studies. January

6 WHITE PAPER 5 From EMRs to Real World Evidence De-identified EMR data is the most relevant data currently available in the Canadian market to use in RWE studies. It follows the patient pathway over time, capturing diagnoses, vital signs, lab test results, time off work, drug identification numbers, programs (smoking cessation programs, medication reviews, telemedicine), smoking status, specialist referrals and more. This data enables studies to be undertaken that follow a typical RCT protocol. The EMR data collected needs to be of the highest standard, epidemiologically relevant and referenced to prescription data in order to demonstrate accuracy and represent the Canadian population as a whole. This data is now available from IMS Brogan for the Canadian market and studies can be undertaken with the Canadian RWE team as part of the global RWE Centre of Excellence. The EMR data collected needs to be of the highest standard, epidemiologically relevant and referenced to prescription data. The steps that need to be undertaken to take EMR data and build an RWE data warehouse are complex and are governed by strict privacy guidelines and regulations. Once this process has been defined and the data warehouse built, the patient dimensions can be extracted and used to undertake Real World Evidence studies. The many inputs to the process are shown in Figure 2. Figure 2 Patient Dimensions to Support RWE Studies Age Int. codes Sex Programs Smoking status ICD-9 Diagnosis Patient Vitals: BP, Pulse, Temp., BMI Rx: DIN, Dose, Refills, Length Lab results Referrals specialty Freq. short-term absence Longitudinal analysis over time Source: IMS Brogan RWE database

7 WHITE PAPER 6 Early planning is required to ensure the quality of responses, rational RWE spend throughout the life cycle, and proactive efforts to differentiate and position a brand. RWE Can Improve Competitive Position Throughout a Brand s Life Cycle The complex logistics involved in fulfilling RWE requirements call for a heterogeneous approach. Fundamentally, early planning is required to ensure the quality of responses, rational RWE spend throughout the life cycle, and proactive efforts to differentiate and position a brand. Success will depend on: Careful and routinely updated analysis of current and future comparators, drilling down to actual/perceived differentiation on specific claims, to enable tactical planning of individual studies to address those differentiation claims A long-term view of supporting a product's claims with analyses of specific data sources, based on early inventory/vetting of databases that could support RWE studies and specific plans to address gaps by creating data sources where they are unavailable A tactical evidence-generation plan that enables prioritization of data acquisition and analyses both to anticipate external demands and to maximize the execution of a differentiation strategy Key RWE Learning from Around the Globe Comparators Pre-launch: RWE should focus on documenting the real-world performance of existing comparators and the standard of care, particularly those related to the endpoints that are central to the Target Product Profile. Patient segmentation and market sizing should also be completed pre-launch. Post-launch: RWE emphasis after launch should shift toward not only replicating RCT efficacy and safety findings in real-world settings, but also seeking explicit head-to-head differentiation from comparators in the real world. In addition to safety and efficacy claims, this should consider product usage characteristics, such as dose adjustments, adherence, appropriate use, and cost consequences of treatment, which can influence the product s cost effectiveness or value equation. By this stage in a product s life cycle, the large body of RWE evidence supporting its safety, effectiveness and use can be viewed as a competitive advantage. Established products: A range of RWE studies can be valuable for established products facing new market entrants or the generic conversion of comparators. By this stage in a product s life cycle, the large body of RWE evidence supporting its safety, effectiveness and use can be viewed as a competitive advantage. Competitive intelligence on the expected profile of new entrants can inspire RWE studies that cement differentiation claims before competitors can launch. RWE can also enhance generic defence strategies, highlighting the magnitude of a product's differentiation to prevent discussions coming down to price reductions alone. Outlook Scenario Real World Evidence will be introduced to the Canadian market in late Pilot studies and stakeholder discussions with federal/provincial/territorial governments, the PMPRB and CADTH will help to build on their recommendations to make use of RWE. As in other countries, the period of mid-2014 to end of 2016 will see the uptake of RWE as a core discipline within pharma and the use of Canadian data especially focused on broadening the scope of limited listings. In the longer-term (2017 and beyond), there will be additional use of RWE to support pay-forperformance agreements, progressive licensing and pharmacovigilance. 372

8 IMS BROGAN, a Unit of IMS MONTREAL Trans-Canada Highway Kirkland (Québec) H9H 5M3 (514) OTTAWA 535 Legget Drive, Tower C, 7th Floor Kanata, Ontario K2K 3B8 (613) TORONTO 6755 Mississauga Road, Suite 200 Mississauga, Ontario L5N 7Y2 (905) ABOUT IMS IMS Health is a leading worldwide provider of information, technology, and services dedicated to making healthcare perform better. With a global technology infrastructure and unique combination of real-world evidence, advanced analytics and proprietary software platforms, IMS Health connects knowledge across all aspects of healthcare to help clients improve patient outcomes and operate more efficiently. The company s expert resources draw on data from nearly 100,000 suppliers, and on insights from 39 billion healthcare transactions processed annually, to serve more than 5,000 healthcare clients globally. Customers include pharmaceutical, medical device and consumer health manufacturers and distributors, providers, payers, government agencies, policymakers, researchers and the financial community. Additional information is available at We understand the Canadian healthcare market, and your issues. We can help you connect knowledge across all aspects of healthcare. For additional information on our IMS Brogan solutions, please contact your account representative. For more information on RWE, please contact Neil Corner, ncorner@ca.imsbrogan.com IMS Health Incorporated and its affiliates. All rights reserved. Trademarks are registered in the United States and in various other countries.