The Pharmaceutical Research and Manufacturers of America (PhRMA) has toughened up its commitment to transparency and ethical conduct in clinical research by revising the Principles on Conduct of Clinical Trials and Communication of Clinical Trial Results first published by the industry association in 2002.

The revisions to PhRMA’s voluntary code are something of a pre-emptive strike. The announcement coincided with a public meeting held by the US National Institutes of Health on 20 April to discuss future regulations on expanding the Institute’s trial registry and results databank, ClinicalTrials.gov., as required by the Food and Drug Administration Amendments Act of 2007 (FDAAA).

The amendments build on revisions already made to the PhRMA Principles in 2004 and come around five months after the International Federation of Pharmaceutical Manufacturers and Associations updated its Joint Position on the Disclosure of Clinical Trial Information via Clinical Trial Registries and Databases, widening the scope of mandatory disclosure for efficacy studies.

The revised Principles, which take effect on 1 October 2009, commit PhRMA’s member companies to “the timely submission and registration on a public database of summary information about all clinical trials that we conduct involving the use of our marketed or investigational products in patients”. ‘Timely’ is taken to mean within 21 days of enrolling the first patient, as is the general requirement under the FDAA.

This commitment extends to some early Phase I studies, PhRMA notes. However, the specification that these are clinical trials involving “patients” indicates that industry is still reluctant to make most Phase I information public. It has previously cited concerns about commercial confidentiality, and the revised Principles further argue that disclosure of Phase I studies is in the main unlikely to benefit researchers or the public.

Some “very early exploratory clinical trials (i.e., most Phase 1 studies) typically involve limited testing in a small set of healthy adults, and therefore do not generally provide robust information regarding safety or effectiveness”, they state. “Because these studies typically involve healthy adults, a clinical trial registry would not be useful for patients seeking to enter such trials. In addition, due to their small size, and because such studies would not provide safety or effectiveness data in actual patients, results information would be limited.”

The Principles do, however, widen the scope of results disclosure by committing to post summary results of all clinical trials (as before, regardless of outcome) in patients with not only drugs that have been approved for marketing, but also those whose development programmes have been discontinued.

A “discontinued” programme is characterised as one where “the company is no longer studying the applicable molecule, does not expect to resume development, and has no plans for the molecule on its own or
through collaboration or out-licensing”.

PhRMA also says that if information from any clinical trial “is felt to be of significant medical importance, then we will work with investigators to publish the data”.

Authorship standards

Among other significant changes in the revised Principles, the US association has tackled concerns about ghost-writing of research papers by adopting the authorship standards of the International Committee of Medical Journal Editors (ICMJE). This means only individuals who make substantial contributions to medical manuscripts will be recognised as authors.

PhRMA has also aligned the Principles with ICMJE standards on the disclosure in medical manuscripts (both articles and letters) of any financial or personal relationships that may represent a conflict of interest. In addition, authors of journal manuscripts are asked to describe the role of the sponsors in designing the study, collecting and interpreting data, and writing the ensuing report.

“Our member companies have a longstanding commitment to ethical conduct of clinical trials and to transparency of reporting,” commented PhRMA president and chief executive officer Billy Tauzin.

“But, we’ve heard the calls that we could do more. And these revised Principles, which come on the heels of our updated Code on Interactions with Healthcare Professionals, further renew our pledge to ‘practice what we preach’.”