New AAMC Principles for Protecting Research Integrity: A Small Step For Medical Research

In last month's American Association of Medical Colleges (AAMC) Reporter was a notice of the new AAMC Principles for Protecting Integrity in the Conduct and Reporting of Clinical Trials (The full document is here.)

The Principles contain some good bits. For example, they insist that a multi-site randomized controlled trial should have a publication and analysis committee which should have a right to access "any data generated druing the study that the committee deems necessary to ensure the integrity and validity of the study and any presentations based on it." The Principles also declare "ghost or guest authorship is unacceptable."

Had these Principles been in force in the UK (although, admittedly, they were written for the US), they might have averted the messy case at Sheffield University that we just addressed here and here.

However, the Principles are also notable for what they do not say.

In a previous post on Health Care Renewal, we discussed the study bv Mello et al of contracts between commercial sponsors and academic research institutions. The study identified a number of contract provisions that could let sponsors manipulate the design, execution, analysis, dissemination, and discussion of research.

Most of these contract provisions were not addressed by the new Principles.

To illustrate, I will list the provisions mentioned in this previous post (in italics), with comments on how the new Principles do or do not address them. (The percentages after each provision refer to the proportion of medical school contracting officials who would permit that provision in a contract with a research sponsor.)

• The sponsor will own the data produced by the research - 80%
  The principles implicitly allow the sponsors to own the data, but they say that a publication and analysis (P&A) committee should have access to any part of the data it "deems necessary to ensure the integrity and validity of the study...." This committee, in turn, should have a majority of academic members, but can include sponsors' representatives. How the committee should function is not specified.
• The sponsor will store the data and release portions to the investigator - 35%
  Again, the Principles implicitly allow this practice, as noted above.
• The investigators (whether at your site or any other site) are not permitted to alter the study design after the agreement is executed - 68%
  The Principles do not address who designs studies, nor who may alter them. They only state that "any deviations to the pre-specified plan should be identified and discussed."
• The sponsor is permitted to alter the study design after the agreement is executed - 62%
  Again, since alterations of the study are allowed, but who may alter them is not discussed, this is not directly addressed.
• The sponsor may prohibit individual site investigators from publishing manuscripts independently of the sponsor or group - 15%
  The Principles state "individual site investigators in a multisite trial should be free to analyze and publish data from the individual site, consistent with sound principles of analysis, but only after publication of the study as a whole and after review and comment (but not approval) by the P&A committee, or, in the absence of acceptance of the full publication, within 18 months from the specified end points or earlier termination of the study." So the Principles seem to prohibit this provision.
• The sponsor may include its own statistical analysis in manuscripts - 24%
  The Principles include a statement that "the P&A committee of multisite clinical trials (or the principle investigator of a single site study) should require that the sponsor of the study perform its analysis of trial data in a defined period of time." Thus, the Principles implicitly allow the sponsor to do the primary analyses of study data, and hence do not directly contradict this provision.
• The sponsor will write up the results for publication and the investigators may review the manuscript and suggest revisions - 50%
  Although the Principles state that all people who have a role in authoring manuscripts accurately disclose these roles, they do not specify who should be primarily responsible for manuscripts. They also explicitly say "it is acceptable for an employee of the sponsor to participate in drafting and publication activity, if fully disclosed." Thus the Principles do not contradict this provision.
• While the trial is going on, the investigators may not discuss research results (including presentations at scientific meetings) with people not involved in the trial - 66%
  The Principles do not address this provision at all.
• After the trial is over, the investigators may not discuss research results (including presentations at scientific meetings) until the sponsor consents to dissemination - 21%
  The Principles state that "the P&A committee or PI should make a good faith effort to disseminate results of the study through peer reviewed mechanisms," and that "researchers and their institutions have an ethical obligation when conducting human research to seek to make the results available publicly," and that "all trials meeting the ICMJE requirements for registration should make their results publicly available ... within 18 months of submission of a manuscript for publication." However, nothing in the document prevents the sponsor from otherwise exerting control over dissemination.
• The terms of the clinical-trial agreement are confidential - 62%
  The Principles do not address this provision.
• After the trial is over, the industry sponsor may prohibit investigators from sharing raw research data with third parties - 41%
  The Principles state "the sponsor, the investigators, and their institutions should a adopt a model for data sharing, post publication, similar to that of NIH." They do not further specify the NIH model.

Although these new AAMC Principles for Protecting Integrity in the Conduct and Reporting of Clinical Trials are a step forward, they are but one small step. Unfortunately, these principles fail to address many of the egregious contract provisions that commercial firms that sponsor research insert in contracts made between them and medical schools or academic medical centers in the US. Until more is done, commercially sponsored clinical research done in the US remains potentially under the control of the sponsors, rather than the academic "principle investigators."
I wonder how many patients would sign up as research subjects if they knew that the research was controlled by the company who made the drug or device being studied, rather than by the white-coated academic researchers?