DIA GCP/QA SIAC All Member Meeting Pamela Rose Takeda Global Research and Development Inc.

Clinical Trial Transparency is Here to Stay… Researchers are required to disclose clinical trial protocol information and results Many stakeholders (academic centers, governmental agencies, patient advocacy groups, etc) WHO recommends registration of all trials Every year, more countries are requiring registration and results disclosure 23 April 2009

Some of the Challenges… Transparency without compromising drug development Global, multi center trials Multiple country registrations with varying requirements (content, timing) Results format varies by country Consistency of information Update one country registration; update them all Documentation of registration Company processes Process for posting results on clinicaltrials.gov 23 April 2009

PhRMA Principles updated Announced at the NIH Public Meeting 20 April 2009 Effective October 1, 2009 Register all clinical trials involving patients Post results summaries for all clinical trials involving patients for approved medicines as well as medicines whose research programs are discontinued. 23 April 2009

NIH Public Meeting Issues for Discussion Post results of unapproved products? Post data summaries without being misleading or promotional? Post non-technical summaries? What information? Who should write them? Post full protocol? Procedures the Agency should consider for QC Increase results posting timing to 18 months after LSLV of Primary Outcome? Post results for studies registered before effective date of the regulation? Appropriate timing for registration updates Standard format for submission of required basic results Statement that should accompany voluntary registrations Other 23 April 2009

NIH Public Meeting Pre-registered Speakers Katie McCarthy: BIO Francis Crawley: GCP Alliance Lisa Griffin Vincent: AdvaMed Edward Campion: NEJM Gordon Johnston: GPhA William Vaughan: Consumers Union Jeffrey Francer: PhRMA Howard Rutman: Taro Pharmaceuticals Inc. Carlea Bauman: C3 Colorectal Cancer Coalition 23 April 2009

NIH Public Meeting Key Points Submit comments to the Docket until 22 June 2009 NLM 71,398 Trials registered on CTgov 678 results submitted Expect results will be clear, informative and will be understood by someone who doesn’t know about the trial FDA 7 working groups implemented Challenges include unclear language, technical issues, unrealistic statutory deadlines, integration of NLM and FDA procedures, multiple stakeholders 23 April 2009

NIH Public Meeting Key Points BIO Post ICH E3 synopsis Post results from trials discontinued due to safety issues Information posted should be useful and understandable GCP Alliance Post results of all trials Post complete protocol 23 April 2009

NIH Public Meeting Key Points AdvaMed Post results of trials discontinued for safety reasons Create text/check box for waiver/delay No posting of complete protocol Add text area on SAE section NEJM Posting results on CTgov will not be a barrier to publishing on NEJM Results posting should Not include narrative summary; risk of overinterpretation Post AE Facts only; distinguish between major and minor effects 23 April 2009

NIH Public Meeting Key Points GPhA Generic Bioequivalence studies should not be registered Consumers Union Results should be public Register phase 1 trials Narrative summaries cannot be trusted FDA should hire scientists to review data and write narratives Collect full protocol; release if requested Post results within 1 year LPLV 23 April 2009

NIH Public Meeting Key Points PhRMA Register trials conducted in patients Post results summaries for all clinical trials involving patients for approved medicines as well as medicines whose research programs are discontinued Post technical ICH E3 synopsis Study best way to generate lay summary AE information should be consistent with FDA requirements Do not post full protocol 23 April 2009

NIH Public Meeting Key Points Taro Pharmaceuticals Bioequivalence studies for generics should not be registered prior to approval C3 Colorectal Cancer Coalition Results should be understandable Results should all be in one database Canadian Representative Consider international format/impact 23 April 2009

NIH Public Meeting Key Points King and Spaulding AE %/frequency should be presented on the table instead of requiring reader to calculate Consumer Advocate/Journalist Post all results, especially early stage failures Include narrative summary 23 April 2009

Contact Information Pamela Rose Associate Director, Clinical Trial Registration and Results Disclosure Takeda Global Research and Development Inc. Pamela.rose@tgrd.com Office: 847-582-5758 23 April 2009