Regulatory Science Symposium: Clinical Trials Hurdles Session 5 - Clinical Trial Data Disposition, Results, and Transparency Group (2015)

Clinical trials results: data disposition and transparency

• Data disposition--where does all the data go?
  • Newspapers/headlines
  • Press releases
  • Clinical study report (CSR)
  • Abstracts/manuscripts
  • Registries such as www.clinicialtrials.gov
  • Submitting reports to regulatory authorities around the world such as IND, NDA/MAA
• Develop press release
  • Good - positive results and action plan and gain founding
  • Bad - negative results and individuals may stop using those medicines
  • Two audiences ie. investors, lawyers, other businesses, search engines
• Author clinical study report
  • A standard available for producing a report: ICH E3- structure and content of clinical study
  • De facto standard
  • Most transferable
  • Globally accepted and easy to use
  • Flexible for phase I studies
  • CSRs consists of the following:
    • Protocol element
    • Patients disposition
    • Data disposition
    • Statistics output
• Publications
  • Abstracts
  • Manuscripts not critical in industry and they will develop marketing materials later on
• Sharing results with sites/subjects
  • Press release
  • Tell those who are in the study how it went so no one is unaware
  • We do not have a good process for this, but putting into clinicaltrials.gov might assist with this objective
  • Sites are responsible to tell the subjects what the results are
• Submitting reports to regulatory authorities
  • US IND
  • National health authority of other countries (if required)
  • As part of marketing application (NDA/MAA)
• When do we submit study results/reports?
  • During development
    • Of an investigational new drug or clinical trial application (IND or CTA)
      • To support other clinical investigations
      • With IND annual reports
      • Informational amendments
      • Fulfill post-marking agreements- PMR/PMC
• Data repositories
  • Exist all around the world
  • Government sponsored
    • Clinicaltrials.gov
      • Transparency initiative
      • Basic uses - identify trials of potential interest for specific individual, track process of specific trial, identify ongoing and terminated/completed trials, identify investigators/research members for certain studies
    • National Institute of Health clinical data repository (NIH CDR)
      • Includes all clinical electronic data from 1975 to present
      • Updated daily and publicly funded
  • Industry/company sponsored (new)
    • Mandatory reporting
    • Voluntary participation
      • Principle for responsible clinical trial data sharing
      • Includes data from approved and non-approved drugs
  • Public-private partnership
    • Database for the aggregate analysis of ClinicalTrials.gov (AACT)
    • Issue: No idea where the data is aggregated from, questioning the quality of the data
  • Industry/company sponsored
    • PhRMA and EfPIA
    • Biopharma companies are committed to enhancing public health through responsible sharing, yet also not violating the patient privacy, integrity of regulatory systems, and maintaining incentives for investment in biomedical research
    • Look for trends to lobby around
  • Clinical trial data sharing is relatively new
    • Must vet investigators etc.
  • Background in the US
    • Suppression of research results led to safety issues and prevent innovation
  • Reasons to register clinical trials and report results
    • Human subject protections
    • Research integrity
    • Evidence based medicine
    • Allocation of resources
  • History of ClinicalTrials.gov
    • FDAMA 113 (1997): mandates registry
    • Launched site in Feb. 2000
    • FDAAA 801(2007): expands registry and adds results database
    • Still requires phases II-IV drug and device trials for all diseases
    • Requires result reporting (2008)
      • Basic results, expansion of results, FDA-approved trials
    • Added enforcement provisions
  • Clinicialtrials.gov
    • Report summary trials at trial completion for
      • Trials of devices
        • Small feasibility studies are exempt
      • Trials of drugs and biologics
        • Phase I investigations are exempt
  • Trial reporting:
    • Register study before first participant is enrolled
    • Keep entries up to date
    • Subject to FDAAA
  • Basic results reporting requirements
    • Submission within 12 months of the earlier of estimated/actual primary completion date
    • Can postpone results due to marketing but will have to post them eventually
  • Uses of ClinicalTrials.gov 
    • Audience: volunteers, finding a new drug, finding a center of research for a given condition/intervention

Accompanying text created by Annie Ly | Undergraduate Research Associate and Provost's First Generation Research Fellow | lyannie@usc.edu