1. 1 PRIORITY MEDICINES FOR EUROPE AND THE WORLD Barriers to Pharmaceutical Innovation Richard Laing EDM/PAR WHO

2. 2 Barriers to Innovation: Background Cost and duration of medicines development have increased –Many projects in early development stages, but not enough of this potential innovation is being translated into market approvals. For some diseases, there remains an inadequate understanding of basic science, and potential targets for medicines development have not been identified.

3. 3 Recent Publications Three papers published almost simultaneously, plus commentary on Priority Medicines website –EMEA: Discussion Paper: The European Medicines Agency Road Map to 2010: Preparing the Ground for the Future –FDA: " Challenge and Opportunity on the Critical Path to New Medical Products" –Perspectives – "Cutting the Cost of Drug Development?" M.D. Rawlins –Sue Middleton: GSK Commentary on "Barriers to Innovation"

4. 4 Barriers to Innovation: Suggested Solutions All authors agreed that every aspect of the regulatory process should be re-examined and that the evidence base for regulatory practices should be critically analysed using modern methodologies. Preclinical studies –Many old tests and methods –New analytic tools needed –Validation of old methods required Clinical Studies –Regulatory authorities are risk averse so the RCT has become the gold standard –Other approaches even using historical controls may be possible and desirable

5. 5 Neglected Areas: Post marketing Surveillance and Patients All papers neglect Phase IV studies as a part of the innovation process. Great opportunities for Europe from use of electronic data bases for Phase IV studies on both efficacy and safety Apart from the industry paper, none of the three other papers mention any role for patients in this review. They are referred to as beneficiaries of the process but never as contributors to the decision-making.

6. 6 Key Unanswered Question? What should be the role of patients, patient organizations and consumer organizations in promoting innovation? Patients have been very effective in AIDS and orphan disease drug development. Patients are involved in the development of treatment guidelines for NICE

7. 7 A "barriers to innovation" Research Agenda Bottlenecks and barriers in the current medicines development process are to be identified and solutions elaborated to overcome them. –Range of stakeholders required: academia, clinicians, patient organizations, large and small industry, regulatory and ethics specialists –Every requirement within the medicines development process whether clinical or preclinical should be questioned for its regulatory relevance, costing, and predictive value. –The involvement of the EMEA and the various European national regulatory agencies and their scientists is critical to this initiative. –6 th Framework already has issued a call closing November 16th

8. 8 PRIORITY MEDICINES FOR EUROPE AND THE WORLD Comparative Clinical Trials Warren Kaplan

9. 9 Comparative Trials: Background For most medications at launch, we know little about whether or not a given medication is better value for the money than alternatives. –This knowledge gap exists because most drug regulatory authorities do not examine "value for money" For most medications at launch, clinical trials are not designed to look at whether or not a given medication is better than another drug. Typically, efficacy is measured versus a control which is often, but not invariably, a placebo lacking any active ingredient. –Many registration authorities do require comparative benefit studies To estimate comparative benefit between two medicines, large (time consuming and expensive) trials are needed since there are often small differences between treatment outcomes when comparing the interventions.

10. 10 Comparative Trials: Who should pay for them and who conducts them? Industry? Government? Or… Private insurers and the government could set aside some fraction of their annual medicines spending to endow an organization to provide an independent source of reputable research into comparative effectiveness and cost. –Electronic prescription and medical databases to conduct Phase IV and/or pharmacoepidemiologic studies in place of controlled, comparative clinical trials. –EU has a great comparative advantage over the USA as this kind of electronic linkage of prescribers and medical records is still fragmented in the USA –Phase IV studies could add a randomization step ("randomized epidemiology")

11. 11 Comparative Trials/ Comparative Effectiveness Europe 2005: "An information society for all", available at http://europa.eu.int/information_society/eeurope/2002/news_lib rary/documents/eeurope2005/eeurope2005_en.pdf. This Action plan on "electronic health" should be used as a way of creating post-marketing studies to better understand comparative effectiveness and cost-effectiveness.