PhRMA Introduces Revised Principles on Conduct of Clinical Trials and Communication of Trial Results

On April 20, 2009, the Board of Directors of PhRMA¹, the Pharmaceutical Research and Manufacturers of America, released a revised Principles on Conduct of Clinical Trials and Communication of Trial Results (Principles), last revised in 2004.

PhRMA states that changes to the Principles, which are to take effect October 1, 2009, propose to:

• Increase transparency in clinical trials
• Enhance standards for medical research authorship
• Improve disclosure to manage potential conflicts of interest in medical research

Increased Transparency in Clinical Trials

• The new Principles call for disclosure of results from all clinical trials conducted in patients involving the use of products approved for marketing or investigational products whose development programs are discontinued, regardless of outcome.
• Therefore, some Phase I studies are now covered, whereas the previous principles excluded all “exploratory studies.”
• The Principles encourage disclosure of clinical trial results for products whose development has been discontinued, whereas the previous principles included only marketed products or products approved for marketing.
• The Principles define when development has been discontinued, stating “a development program is discontinued when 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.” Therefore, discontinuation is a molecule-based determination. Terminating development in certain indications or certain formulations would not constitute discontinuation under the new Principles. Furthermore, it appears that companies can delay disclosure of results with respect to terminated programs as long as there is an expectation that development will resume in the future or if the molecule is available for partnering or out-licensing.
• In the new Principles, PhRMA removed one statement that sponsors have discretion to determine who will have access to the sponsor’s study database and another statement that study databases generally are made available only to regulatory authorities. In their place, the new Principles state, “We seek to provide investigators with meaningful access to clinical data from the studies in which they participate.”

Enhanced Standards for Medical Research Authorship

• The new Principles regarding authorship conform to the International Committee of Medical Journal Editors (ICMJE) standards.
• Specifically, the new Principles provide more guidance on identifying who should and should not be an author and identifying sources of support for the clinical trial:
• For multi-center trials, the Principles specify that the multi-center group should identify the individuals with direct responsibility for the manuscript.
• Clinical investigators who do not make substantial contributions to the medical manuscript should not be authors, but instead should be acknowledged as “clinical investigators” or “participating investigators,” and the publication should include a description of their role in the clinical trial. The Principles further specify, “acquisition of funding, collection of data, or general supervision of the research group, alone, does not justify authorship.”

Improved Standards to Manage Potential Conflicts of Interest

• Consistent with PhRMA’s recently updated Code on Interactions with Healthcare Professionals, the new Principles circumscribe certain payments to clinical investigators and explicitly state that resorts are not appropriate venues for meetings related to a clinical trial. Nor should sponsors “provide recreational or entertainment events in conjunction with these meetings” or “pay honoraria or travel or lodging expenses for those who are not involved in the clinical trial.”
• The new Principles state that sponsors should recognize and support clinical investigators in meeting their standards and ethical obligations, including authorship:
• Authors are responsible for disclosing all financial and personal relationships that might bias their work and should state explicitly whether potential conflicts do or do not exist.
• Authors should (1) identify individuals who provide writing or other assistance and (2) disclose the funding source for this assistance.
• Authors should describe the role of the study sponsor (or state that it had no role) in any aspect of the study from design to the writing of the report and in the decision to submit the report for publication.

Conclusions

• The new Principles provide for expanded disclosure of clinical trial results, primarily by including Phase I clinical trials conducted in patients and clinical trial results for products whose development programs are discontinued.
• The new Principles conform to the ICMJE standards on authorship of clinical trial publications with the goal of ensuring that only individuals who make substantial contributions to the publication will be recognized as authors.
• The new Principles also improve standards with regards to conflicts of interest, including alignment with ICMJE standards for disclosure of potential conflicts.

Voluntary codes often become the “standard of practice” for the underlying conduct, such that compliance can become the expected norm against which conduct and expectations are judged by legal and regulatory authorities. Consequently, prudent clinical trial sponsors should review their internal processes and procedures and begin training their personnel in order to conform to the new Principles before their October 1, 2009 effective date. In addition, both sponsors and clinical trial sites should revisit their forms of clinical trial agreements in light of the revised Principles. 

¹ http://www.phrma.org/

Legal News Alert is part of our ongoing commitment to providing up-to-the-minute information about pressing concerns or industry issues affecting our clients and colleagues.

If you have any questions about this alert or would like to discuss the topic further, please contact your Foley attorney or the following:

David A. Charapp
Special Counsel, Private Equity & Venture Capital Practice
San Diego, California
619.685.4606
[email protected]

Leslie B Overman, Ph.D.
Associate, Biotechnology & Pharmaceutical Practice
San Diego, California
858.847.6816
[email protected]

Judith A. Waltz
Co-Chair, Life Sciences Industry Team
San Francisco, California
415.438.6412
[email protected]