Introduction to Drug Development

Transcription

1 Introduction to Drug Development Yves Geysels, PhD Head Clinical Research Operations, Belgium Past President of the Associoation of Clinical Research Professionals (ACRP) Board Member of the European Forum for Good Clinical Practice (EFGCP)

2 Objectives Understand the complex process of Drug Development Some Facts and Figures Stages in the discovery and development of a new medicine Quality standards Current Clinical Research Environment and Trends 2 Introduction to Drug Development, Yves Geysels EACPT Gent, Aug 2007

3 Facts and Figures About 12,000 molecules in various stages of R&D Up to 20,000 clinical trials/yr/ww. Up to 1,5 Mio pts included Only 1 out of 5-10,000 molecules will become a NMP NMP reach the market /yr 1 NMP= yrs of research and cost approx. 630 Mio 1 NMP is studied in approx. 80 clinical trials Source: J.P.Tassignon, training investigators in the conduct of clinical trials, ECLIN, Introduction to Drug Development, Yves Geysels EACPT Gent, Aug 2007

4 Industry spends more to get less Industry R&D Expense ($ Billions) Source: Source: FDA CDER & CBER; Evaluate Annual NME Approvals $40 $35 $30 $25 $20 $15 $10 $5 $0 R&D Investment NME Approvals Introduction to Drug Development, Yves Geysels EACPT Gent, Aug Thanks to John Orloff

5 Source: Borrowed from APBI, A-Z of Medicines research, 4th ed, April Introduction to Drug Development, Yves Geysels EACPT Gent, Aug 2007

6 Pharmaceutical R&D Staged drug development Research Toxicology Phase I Phase II Phase III Phase IV PK Efficacy Approval Market Initial safety Safety Multi-phase Sequential Milestone-led 6 Introduction to Drug Development, Yves Geysels EACPT Gent, Aug 2007

7 Staged Drug Development: Phase 0 Purpose: to evaluate precisely the risk of administration to man Effect of molecule on vital organs of animals Potential effects on genes, reproduction, etc Absorbation of molecule in blood Way of being metabolized This information in various animal species, rodents and non-rodents, will be evaluated Extrapolation to man (MABEL, NOEL) 7 Introduction to Drug Development, Yves Geysels EACPT Gent, Aug 2007

8 Staged Drug Development: Phase I Purpose: After a full review of preclinical data this phase tests various doses of the drug in healthy subjects to determine the dose related tolerability and safety and drug absorption and PK Phase I PK studies (ADME) Source: Definition of Clinical Trial Phases (Jones T. BMJ 2001; 322: ) Guide to clinical Trials, Bert Spilker, Raven Press, Introduction to Drug Development, Yves Geysels EACPT Gent, Aug 2007

9 Staged Drug Development: Phase II Purpose: On the base of dose range and PK identified in Ph 1 this phase evaluates the efficacy and tolerability of the drug over a range of doses compared to placebo in patients with the disease Source: Definition of Clinical Trial Phases (Jones T. BMJ 2001; 322: ) 9 Introduction to Drug Development, Yves Geysels EACPT Gent, Aug 2007

10 Staged Drug Development: Phase III Purpose: This phase uses a selected dose from phase II to evaluate efficacy and tolerability of the drug in a large number of subjects compared with placebo or other similar drugs. Required by HAs for approval of a NDA Source: Definition of Clinical Trial Phases (Jones T. BMJ 2001; 322: ) 10 Introduction to Drug Development, Yves Geysels EACPT Gent, Aug 2007

11 Staged Drug Development: Phase IV Purpose: A study that is started after approval and whose primary intention is the support of publications rather than registration or label changes, i.e., results are not intended to be included in a submission dossier. Focus on Pharmacovigilance, Pharmacoeconomics Source: Definition of Clinical Trial Phases (Jones T. BMJ 2001; 322: ) 11 Introduction to Drug Development, Yves Geysels EACPT Gent, Aug 2007

12 Significant new technologies have emerged Protein chips Transgenic animals Proteomics Cheminformatics Pharmacogenomics Bioinformatics Source: Strategic Planning Pharma Molecular modelling Functional genomics 12 Introduction to Drug Development, Yves Geysels EACPT Gent, Aug 2007 In silico experimen tation

13 which trigger a paradigm shift in R&D and medicine From... To... Clinical definition of disease diagnosis Molecular definition diagnosis and predisposition 13 Introduction to Drug Development, Yves Geysels EACPT Gent, Aug 2007

14 AND we need new medicines... Critical Path Initiative, FDA Innovative Medicines Initiative, EU Risk New Clinical Trial Paradigm FIM, Exploratory CTA 14 Introduction to Drug Development, Yves Geysels EACPT Gent, Aug 2007

15 Pharmaceutical R&D The New Paradigm Target discovery and validation PoC clinical trials Clinical development Exploratory Phase Confirmatory Phase Target Proof-of-Concept Efficacy Approval Market Safety Adaptive Parallel Data-led 15 Introduction to Drug Development, Yves Geysels EACPT Gent, Aug 2007

16 Comparison of Adaptive Seamless Trial Design with Separate Phase II and III Trials Learning Confirming Standard 2 phases A B C D Control Planning & Designing Phase III Adaptive Seamless Design A B C D Control Learning, Selecting and Confirming Dose Selection 16 New trends and paradigms in CR&D Yves Geysels May 30, 2007 Personal

17 Definition Adaptive Design (AD) Trials Is a trial which incorporates the possibility of modifications in the trial design according to pre-specified rules, based on data collected from the ongoing trial. Seamless Design Trials Is one which combines what normally would be considered two separate sequential trials into a single trial. If there is some form of adaptation and the data from both trials (or stages) of the seamless design are combined, then the trial is an Adaptive Seamless Design (ASD) Trial 17 New trends and paradigms in CR&D Yves Geysels May 30, 2007 Personal

18 Changing Paradigm Flexible Trial Guidance Multi-Phase Sequential Milestone-led Adaptive Parallel Data-led 18 Introduction to Drug Development, Yves Geysels EACPT Gent, Aug 2007

19 The Key Development Challenges Vision: Transform drug development through integration of innovative approaches and technologies in close partnership with Regulatory Authorities. Science & Technology Safety External Stakeholders Communication & Training Integrate relevant scientific and technological advances, optimize data integration, sharing and mining Improve evaluation systems to detect potential signals earlier and manage risk effectively Engage HAs regarding studies and policy for use of new technologies in drug development Provide effective and innovative strategies and tools for communication and training 19 Introduction to Drug Development, Yves Geysels EACPT Gent, Aug 2007

20 Rapidly changing external environment Over the next two decades there will be a revolution in medicine this advance may be as great as in the past two millennia. Financial Times, May 2006 Societal expectations Technology Information availability Patients, healthcare providers, regulatory authorities, payors, ageing population IT, nanotechnology, genetics, biosensors, drug delivery, imaging Internet, patient groups, home diagnostics, publishing of clinical trials, data mining 20 Introduction to Drug Development, Yves Geysels EACPT Gent, Aug 2007

21 Key drivers to transform the Development model Modeling and Simulation Rapid compound selection in man Biomarkers Innovative clinical trial design Integrated safety assessment and risk management Novel approaches for targeted and innovative therapies Technical innovation Quality by design manufacturing 21 Introduction to Drug Development, Yves Geysels EACPT Gent, Aug 2007

22 Quality Standards All clinical trials, whatever the phase, must be conducted according to the medical professional code of ethics, the guidelines on Good Clinical Practice and the applicable laws. Detailed International Directives and Guidelines GMP QA and SOP Inspections 22 Introduction to Drug Development, Yves Geysels EACPT Gent, Aug 2007

23 Summary The Environment in R&D is changing with increasing Innovation and thus increased Costs Productivity is declining therefore we need a new Paradigm for R&D. FDA s CPI / IMI advocates innovative, flexible trial designs to speed up the clinical development Process. 23 New trends and paradigms in CR&D Yves Geysels May 30, 2007 Personal

24 Thank you for your attention!

25 Last Updated: Wednesday, 15 March 2006, 09:52 GMT BBC NEWS:VIDEO AND AUDIO Hear more about the clinical drug trials this to a friend Printable version Six taken ill after drug trials The six are being treated at Northwick Park hospital BBC LONDON Travel, features and more from the BBC website for London Six men remain in intensive care after being taken ill during a clinical drugs trial in north-west London. The healthy volunteers were testing an anti-inflammatory drug at a research unit based at Northwick Park Hospital when they suffered a reaction. SEE ALSO: 'They say he needs a miracle' 15 Mar 06 Health Q&A: Drug trials 15 Mar 06 Health Confusion over drug trial rights 26 Feb 06 Health Woman died on cannabis drug trial 12 Dec 05 South Yorkshire Drug research openness promised 06 Jan 05 Health Relatives are with the patients, who suffered multiple organ failure. Two men are said to be critically ill. An investigation has begun at the unit, run by Parexel, which said it followed recommended guidelines in its trial. The men were being paid to take part in the early stages of a trial for the drug to treat conditions such as rheumatoid arthritis and leukaemia until they were taken ill on Monday within hours of taking it. Eight volunteers were involved, but two were given a placebo at the unit which is on Northwick Park Hospital's grounds but is run independently. This is an absolutely exceptional occurrence - I cannot remember anything comparable Richard Ley, Association of the British Pharmaceutical Industry 25 Introduction to Drug Development, Yves Geysels EACPT Gent, Aug 2007 RELATED BBC LINKS: Clinical trials