More disclosure Sponsors also face stiff penalties under FDAAA for failing to comply with requirements for posting clinical trial results
on the clinicaltrials.gov/ database. The result has been a surge in trial listings in the system operated by the National Library of Medicine (NLM)
at the National Institutes of Health (NIH); the database now has information on more than 71,000 studies, more than half involving
drugs and biologics. Sponsors continue to object to posting full information on most Phase I trials, and generics firms oppose
listing bioequivalence studies, but other contentious issues have been resolved. The next big challenge is to clarify policies for posting the results of listed studies. Sponsors have been submitting results
information since last fall, creating a database that now has some 700 records, more than 400 from industry sources. Submissions
at this time consist of tables listing basic results, which includes demographic and baseline characteristics of participants
and primary and secondary outcomes, in both cases for the full trial and for each study arm. Reports on serious and frequent adverse events have to be added to the database beginning in September 2009. FDAAA calls for
providing this data in a tabular format, but it's not obvious that the information is useful to patients or researchers. Sponsors
seek clarity on what events are considered "serious" and on time frames for submitting AE reports; one hope is to gain more
synergy in AE reporting requirements for NIH, FDA, and other entities. A number of thorny policies remain to be worked out by September 2010, as discussed at an NIH public forum held in April to
hear comments from industry and other stakeholders. Key issues are whether results must be filed for discontinued studies;
if sponsor-written narrative summaries would be biased and promotional; and how to harmonize reporting standards with other
countries. Providing narrative summaries of results was the most contentious issue. Consumer advocates and medical journal editors objected
that allowing sponsors to submit summaries of study results creates an opportunity for marketers to publicize not-yet-approved
treatments. Consumers Union proposed that NIH staffers write up objective trial summaries, supported by an additional user
fee on FDA applications. Pharma companies identified the International Conference on Harmonization E3 study synopsis as an
internationally accepted format for technical summaries, but sought assurance that FDA will not charge companies with illegal
promotional activity based on required results disclosure. A related issue is whether providing summaries reduces the need to post full clinical trial protocols. Sponsors fear that
full protocols may reveal proprietary information on how data will be assessed, and also raise privacy issues by disclosing
the names of all investigators and subinvestigators. And pharma companies want leeway to determine which discontinued studies
warrant reporting of results, limiting that primarily to studies dropped for safety reasons. Industry moved to defuse some of the opposition by unveiling a revised version of the PhRMA (Pharmaceutical Research and Manufacturers
of America) voluntary clinical trial disclosure policy, which now supports "timely registration of all interventional clinical
trials involving patients." That still would leave out most Phase I safety studies, which enroll primarily healthy volunteers.
PhRMA also would limit reporting on Phase IV trials to those that are interventional, as opposed to the vast spectrum of observational
studies. Avoiding conflicts PhRMA also supports the authorship standards set by medical journal editors that permit only real contributors to a manuscript
to be listed as authors and require disclosure of sponsor involvement with a study and relationships with authors. These fit
the recommendations for avoiding conflicts of interest in biomedical research proposed in a high-profile report from the Institute
of Medicine (IOM). An expert panel chaired by Bernard Lo, professor of medical ethics at the University of California San
Francisco, advises against researchers claiming authorship of ghost-written publications or accepting any gifts, meals, drug
samples or fees from industry. The report backs full disclosure by physicians and researchers of all payments from pharma companies and other manufacturers
and supports legislation requiring drugmakers to report all payments to health care providers, researchers, and health-related
organizations. There are recommendations for curbing industry support of continuing medical education and efforts to remove
industry influence from organizations developing clinical practice guidelines for practitioners—all proposals that fit well
with the pro-regulatory stance of the new administration. Jill Wechsler is the Washington editor of Applied Clinical Trials, (301) 656-4634 jwechsler@advanstar.com
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