1. The fate of independent drug research in Italy: a cross-sectional study Nino Cartabellotta*, Corrado Iacono*, Sandra Petraglia §, Marco Mosti*, Alessia Cirilli §, Luca Pani § Increasing value and reducing waste in biomedical research conference Edimburgh, 28 th – 30 th September 2015 *GIMBE Foundation § Italian Medicine Agency (AIFA)

2. Bursary assigned by GIMBE Foundation is entitled to my father DISCLOSURE

3. In 2005 the Italian Medicines Agency - Agenzia Italiana per il Farmaco (AIFA) – set up the program on independent drug research, with focus on three areas: BACKGROUND Area 1. Orphan drugs for the treatment of rare diseases and drugs for non-responders Area 2. Head to head comparison of drugs and therapeutic strategies Area 3. Strategies to improve the appropriateness of drug use and pharmacoepidemiology studies

4. From 2005 to 2009 AIFA: -launched 5 call for proposal -approved 207 studies -assigned nearly € 96.600.000 In the AIFA program the registration of studies and the publication of results are not required for receiving all assigned funds Currently no public monitoring has been conducted in order to verify the publication of the results BACKGROUND

5. In March 2015, GIMBE Foundation assigned a bursary to explore the research waste of AIFA program on independent drug research AIFA provided full access to administrative data BACKGROUND

6. To estimate research waste, verifying for each approved study: Registration status in WHO registries Time gap from grant approval to start of study Fate: -Never started -Interrupted -In progress -Concluded Publication status of funded studies AIMS

7. Standardization, merging and check of consistency of 5 different AIFA databases Integrating new information from study protocols and other documents Evaluate publication status: -MEDLINE + Google -CENTRAL, EMBASE, etc -Contacts with principal investigators Evaluate registration status: WHO ICTRP platform METHODS

8. Standardization, merging and check of consistency of 5 different AIFA databases Integrating new information from study protocols and other documents Evaluate publication status: -MEDLINE + Google -CENTRAL, EMBASE, etc -Contacts with principal investigators Evaluate registration status: WHO ICTRP platform Only for 2005 and 2006 calls On 17 September 2015

9. RESULTS Assigned funds n. 83

10. RESULTS Areas of funded studies n. 83 *from 2005 to 2007

11. RESULTS Type of funded studies n. 164 n. 28 n. 15

12. RESULTS 2/3 of studies were not registered 22%42%

13. RESULTS Time-gap from grant approval to start of studies Grant approval Contract with AIFA Administrative approval § Ethical approval Start § From the research center of the PI Mean (± SD)515 (± 318) days* Range 7-2058 days* *Data available for 140/204 (69%) studies started

14. RESULTS Fate of 207 approved studies

15. RESULTS 48 reasons for interrupting 44 studies Waste = € 8.700.000

16. RESULTS 1/3 of studies unpublished yet 22%42%

17. RESULTS Nearly 50% of unpublished studies are concluded 22%42%

18. Some useful information were not available in AIFA database and in research protocols The publication status has been verified only: -for 2005-2006 calls -through Pubmed and Google searches LIMITS

19. Our study provides preliminary information on the fate and publication status of 207 studies approved by AIFA The final results will hopefully be used for redefining selection and funding criteria of studies, in order to maximize value and reduce waste of research CONCLUSIONS