GCP/QA SIAC Member Meeting 19 January 2007 Pamela Rose, Session Chair Clinical Trial Registries and Results Databases: Are you Ready for the Audit? GCP/QA SIAC Member Meeting 19 January 2007 Pamela Rose, Session Chair

Session Presenters Pamela Rose, Director, Clinical Trial Information Registries, TAP Maureen Strange, Clinical Trial Registration Gatekeeper, Lilly Tracy Beck, Clinical Trial Results Gatekeeper, Lilly John McKenney, SEC Associates

Session Learning Objectives Describe the audit plan used for auditing clinical trial registries and results databases. Discuss the lessons learned after auditing clinical trial registries and results databases. Learn similarities and differences of Disclosure audit and FDA audit. Learn the unique processes that may be required when auditing disclosure registries and databases.

What is Clinical Trial Disclosure Clinical Trial Disclosure is providing clinical trial protocol information and results on a publicly accessible website in a timely manner Should not be confused with Phase 4 patient or disease registries

Goals of Clinical Trial Disclosure Provide information sufficient for patients to enroll in clinical trial Enhance accountability and transparency of clinical trial information Provide access to results of clinical trials in a comprehensive and objective manner Improve industry reputation

Acronyms AAMC: Association of American Medical Colleges CTR: Clinical Trial Registry FDAMA: Food and Drug Modernization Act FACT Act: Fair Access to Clinical Trials Act ICMJE: International Committee of Medical Journal Editors IFPMA: International Federation of Pharmaceutical Manufacturers and Associations IOM: Institute of Medicine NIH: National Institutes of Health PhRMA: Pharmaceutical Research and Manufacturers of America WHO: World Health Organization ICTRP: International Clinical Trials Registry Platform

Public Disclosure of Study Information Clinical Trial Life Cycle Part 2: Post Trial Results Part 1: Register Protocol Information Within 21 days of enrollment of first subject One year after trial completion: Marketed drugs clinicaltrials.gov clinicalstudyresults.org

Clinical Trial Disclosure Landscape Inputs PhRMA AAMC IFPMA AMA Ottawa Grp Countries FDAMA-113 NIH Congressional Acts ICMJE IOM WHO-ICTRP States clinicaltrials.gov clinicalstudyresults.org Script Many different organizations have been issuing regulations and guidance related to sharing clinical trial information publicly. Not only does this tie to the FDA Modernization Act of 1997, but also to U.S. legislation, guidance by medical journal editors, the pharmaceutical industry itself, and others. Perhaps the text below can float when arrow touches the associated point? FDA Modernization Act 1997 Section 113: Study Sponsors of serious and life-threatening conditions are required by law to register study information on www.clinicaltrials.gov. Guidance for Industry: Information Program on Clinical Trials for Serious or Life-Threatening Diseases and Conditions, March, 2002 can be viewed at www.fda.gov/cder/guidance/index.htm. NIH: National Institutes for Health: NIH investigators are also expected to input study information into clinicaltrials.gov. FACT Act: Fair Access to Clinical Trials Act (S470). Currently being reviewed in the house and senate. This bill can be found at www.govtrack.us/congress/bill.xpd. ICMJE: International Committee of Medical Journal Editors. Includes 11 journals, including NEJM, Annals, Lancet, JAMA, and others. ICMJE has issued an editorial stating that Study Sponsors must register study information from all hypothesis-testing studies before enrollment of the first subject to ensure acceptance and review of the study results manuscript. This editorial can be found at www.icmje.org/clin_trialup.htm. IFPMA: International Federation of Pharmaceutical Manufacturers and Associations. Members of IFPMA include European, Japanese and US Associations. IFPMA issued guidance stating that Study Sponsors will register study information from all hypothesis-testing studies (all phase 3, and some phase 1,2 and 4 studies) into www.clinicaltrials.gov. www.ifpma.org. PhRMA: Pharmaceutical Research and Manufacturers Association. ­ Issued “Principles on Conduct of Clinical Trials and Communication of Clinical Trial Results.” in October 2002, updated June 2004, and gave guidance stating that Study Sponsors will register study information from all hypothesis-testing studies (all phase 3, and some phase 1,2 and 4 studies) into www.clinicaltrials.gov. These documents can be viewed at www.phrma.org. PhRMA also sponsors a clinical study results database at www.clinicalstudyresults.org. State of Maine has passed legislation (H.P.1141-L.D. 1618 Sec. 1. 22MRSA c. 605) requiring all manufacturers marketing drugs in Maine in the Maine Care and Senior Care programs to register all studies into www.clinicaltrials.gov and pay Maine $1000 per year to cover Maine’s expense for managing this program. IOM: Institute of Medicine sponsored a workshop June 2005 to discuss Clinical Trial Registries, generating a summary paper on developing a national registry. www.iom.edu. AMA: American Medical Association: The AMA supports a national clinical trial registry. Their Journal, JAMA, is a member of ICMJE. Ottawa Group: A group of Researchers, Editors and Meta-analysis groups (Cochrane group) led by Canadian Institutes of Health Research. A Statement outlining a set of guiding principles for the development of trial registers was generated after an open meeting was held October 4, 2004 in Ottawa, Canada. The statement can be viewed at http://ottawagroup.ohri.ca/background.html. WHO: World Health Organization: WHO generated a basic statement on clinical trial registration standards in April 2005 after a consensus meeting held in Geneva. The outcome summarized what should be registered and drafted the basic requirements for a minimum dataset. WHO has instituted a group to develop worldwide standards for registering clinical trials, the International Clinical Trials Registry Platform (ICTRP). Additional information can be found on www.who.int/ictrp/about/details/en/print.html. Users Systematic Reviewers (Cochrane, Oregon) Health Policy Makers Journal Editors Researchers & Funders Consumer Advocates Recruitment (Patients, doctors)

Disclosure History Hope Act 1988 1988 1997 2000 2002 2004 2005 2006 IOM Safety Review VIOXX and PAXIL Matters State of Maine Law Enzi Kennedy Act introduced PhRMA Principles Hope Act 1988 FDAMA 113 Law ICMJE Editorial WHO ICTRP FACT Act clinicaltrials.gov 1988 1997 2000 2002 2004 2005 2006 Register AIDs Studies Register to Publish Register all studies for drugs marketed in Maine Register studies on Serious, Life Threatening Illnesses Registry and Results Disclosure Register all hypothesis-testing studies Registry Standards Law Guidance Law

Current Disclosure Law/Guidance Registration Law FDAMA 113 State of Maine Guidance ICMJE PhRMA IFPMA WHO Results Disclosure Law State of Maine Guidance PhRMA IFPMA

Ensure Accuracy of Disclosed Information Why? To build public trust To comply with law and company policies It’s the right thing to do How? Implement good computer/electronic records practices Apply Quality Control techniques Audit disclosed information for accuracy Audit processes and procedures

Key References Guidance for Industry: Information Program on Clinical Trials for Serious or Life-Threatening Diseases and Conditions, March, 2002 www.fda.gov/cder/guidance/index.htm. ICMJE Editorial, www.icmje.org/clin_trialup.htm. PhRMA “Principles on Conduct of Clinical Trials and Communication of Clinical Trial Results.” October 2002. www.phrma.org. State of Maine Legislation, (H.P.1141-L.D. 1618 Sec. 1. 22MRSA c. 605). IFPMA Joint Statement, www.ifpma.org WHO Statement, www.who.int/ictrp/about/details/en/print.html