Adherence to ethical principles in research is critical for our field. This issue, the fifth published by the MPRC/OUP partnership, reflects the priority we give to this concern. Valid informed consent, voluntary participation, scientific merit, minimizing risk, defining acceptable risk/benefit, equitable subject selection, and institutional review and monitoring authority are central to the conduct of human research, and procedures have been codified and modified over the years. Current status and new data concerning research ethics occupy most of this issue, and we are grateful to Laura Roberts and Laura Dunn for organizing this material into an outstanding theme.
The principles for ethical research in schizophrenia are not new. Criticisms of several aspects of psychiatric research in the past ten years have dramatically focused attention on these issues, leading to an extended public debate. The importance of questions surrounding ethical research with mentally ill participants received special emphasis when the President's National Bioethics Advisory Commission (NBAC) selected mental illness research along with human cloning as the first two issues for study.1
Hot issues several years ago included off-medication research, placebo-controlled studies, pharmacological challenge studies, and validity of consent in persons with psychosis. NIMH responded to these concerns with initiatives to develop research in biomedical ethics, and the field's response is represented by the reports in this issue. New topics have recently come into focus, none receiving more public attention than conflict of interest involving finance.
Together with colleagues, I have had the opportunity to address several of these issues elsewhere. This brief listing will enable the interested reader to evaluate views and potential bias of the editorial office of the Bulletin. We reviewed safety data on medication-free research and concluded that there were methods for the safe conduct of such studies,2 and that concerns of neurotoxicity were not supported,3 a view also shared by Wyatt.4 We showed that challenge studies were an important investigative approach, and the safety of the ketamine paradigm was confirmed.5,6 DeRenzo, Conley, and Love introduced a simple test to document the adequacy of informed consent,7 and a modification of this test is routinely applied in the informed-consent process at the MPRC. An empirical study of decisional capacity for consent suggested that psychotic symptoms were not the primary source of decisional impairment in research participants. Rather, impaired cognition was highly correlated with capacity. And, importantly, capacity for informed consent was improved with an educational informed-consent process.8 We also found that the optimistic bias that influences personal risk perception was less of an issue in persons with schizophrenia than in normal volunteers.9 We were concerned that so many reports cited the Declaration of Helsinki as the basis for ethical review when it seemed unlikely that this was the standard actually used in institutional review. We found Helsinki to be flawed in an important way, with the recent “clarification” creating a more realistic approach to an evaluation of the ethics of placebo substitution studies.10–12 Commentary has also been provided on the NBAC report, research ethics, and financial issues related to the pharmaceutical industry.13–17
The remainder of this editorial will contain a statement on two remaining issues. First, what do we expect authors to declare in relation to research ethics? If the report contains data from human or animal participants/subjects, we expect a statement regarding the review authority. If the review authority adheres to a published guideline, we want the relevant citation. Bernard Fischer's article in this issue outlines the primary statements providing explicit guidelines for the review of human research. And, of course, we need author assurance that any human research was conducted with valid informed consent and voluntary participation.
The second issue concerns conflict of interest. While much discussed of late, there are few published guidelines for editors. And there is little agreement as to what constitutes meaningful disclosure. We anticipate progress in this area, but at present we will use the following guidelines:
- Authors make a declaration of any potential conflict of interest that might influence their report or, if made public, might raise questions or embarrass. The author declaration will appear with the published article. Potential conflicts are to be resolved by the editor.
- Assigned editors and referees are expected to declare any potential conflict that might influence manuscript review. This is not limited to financial issues, but includes personal and professional relationships, competitive work, and the like. Potential conflicts are to be resolved by the editor.
- The editor-in-chief makes a financial conflict-of-interest statement to the publisher. This information is also available in the editorial office and is periodically updated. The present statement is as follows: “I do not hold stock or options in commercial entities concerned with medical products or discovery. I do not belong to any speaker bureaus. In 2004, I received consultation or lecture fees from Solvay, AstraZeneca, Lilly, and Pfizer, with a total of 12,100 USD. In 2005, I have received consultation or lecture fees from Janssen, Pfizer, and Solvay/Wyeth, with a total of 8,250 USD. These activities are approved by the University of Maryland School of Medicine. Members of my family have no holdings that might constitute a conflict of interest.”
There is an ongoing debate as to the most informative statement of personal financial interest. To list everything without stating the amounts is most common, but in my view the least informative. There is not much one can do with a list of a dozen or so companies without specifics. And long lists of small amounts are cumbersome. Interest would be piqued if the person listed substantial holdings in a company, patent ownership, or large fees or stock options. The Bulletin prefers this approach, but the definitions of “large” and “substantial” have not yet been set by consensus. So, for now, the editor-in-chief will report as above and will single out any single source exceeding 10,000 USD or a 5% ownership threshold (following proposed reporting guidelines at Harvard). The editor-in-chief will expect assigned editors, referees, and authors to list potential conflicts, being explicit as to financial sums when exceeding the 10,000 USD/5% ownership threshold.
As progress and consensus on conflict-of-interest reporting for medical journals is achieved, the Bulletin will consider modifying its approach. In the meantime, suggestions and comments on the full range of issues in ethics relating to our publishing responsibilities are welcome.