References and Resources
(1) Principles for Protecting Integrity in the Conduct and Reporting of Clinical Trials, Association of American Medical Colleges, 2006 (PDF)
(2) Protecting Subjects, Preserving Trust, Promoting Progress: Policy and Guidelines for the Oversight of Individual Financial Interests in Human Subjects Research, Association of American Medical Colleges, 2001 (PDF)
(3) Clinical trial registration: A statement from the International Committee of Medical Journal Editors, Annals of Internal Medicine, 2004 (PDF)
(4) Is this trial fully registered?: A statement from the International Committee of Medical Journal Editors, 2005
(5) Clinical trial registration: Looking back and moving ahead, 2007
(6) Developing model language for disclosing financial interests to potential clinical research participants, KP Weinfurt et al, IRB: Ethics and Human Research, 2007
When conducting industry-sponsored research, research teams should agree upon the research plan prior to the start of the research. This can help promote objectivity in research and avoid conflicts between investigators and sponsors.
Research plan: Research teams, especially those involving representatives from industry and academia, should discuss and agree upon research methods, including data selection and statistical analyses prior to data collection to avoid bias in the research process. These terms are especially important for investigators who might be authors on papers describing the results of the study. Therefore, the mutually agreed-upon standards should be included in a contract, and investigators should be involved in any amendments to this agreement.
Data access and analysis: The research team should designate a research committee or a principal investigator (PI) for the purpose of coordinating data access and analysis (1). One approach to achieve this goal is for the PI and other key investigators in a study with industry to work directly with the statisticians and others to access the database, ask questions, and challenge conclusions before finalizing the study results.
When conducting industry-sponsored research, regard all significant financial interests in research involving human subjects as potentially problematic and thus as requiring close scrutiny (2). In research involving human participants, investigators should be aware that more stringent institutional review and oversight is appropriate, and many institutions apply such stringency.
Types of human subjects research: There are many types of research involving human participants from basic research to clinical trials. Even within the realm of clinical trials, different benefits, risks, and protections occur. For example, medical device and surgery research can have different profiles of risks and rewards than pharmaceutical research. Phase III trials may pose greater potential for financial gain; however, there are more protections against bias due to the fact that they are larger, conducted at multiple centers, and are double or triple blinded. Phase I trials may be more susceptible to the influence of single investigators, but may be impossible without a committed investigator who also comes with financial interests (for example, the inventor of the technology being tested). Even when it is possible to exclude an investigator with financial interests, it may not be in the best interest of the public if that conflicted investigator has the most knowledge and expertise to carry out the study. For example, the researcher may be a surgeon who has developed a unique surgical technique. All of these issues should be considered.
Rebuttable presumption: Investigators in human subjects research should not play a role (absent compelling circumstances) when they have significant financial interests in the outcome of the research (2). If compelling circumstances exist and an investigator with significant financial interests is involved, he alone should not determine experimental design or data analyses. These aspects of the study should be decided by review mechanisms that utilize investigators without significant financial interests in the study outcome. The balance of benefits and risks to patients and the research should be considered by both institution and investigator in every case. Phases of clinical trials have different benefits and risks, and each case should be judged on those circumstances.
Disclosure to human research subjects: Investigators should be aware that some institutional review boards may require that information regarding relevant financial relationships be disclosed to patients and human research participants.
Tool. Model patient disclosure language developed through a study funded by NIH on disclosure of financial interests to human research subjects (PDF) (6)
Adherence to research plan: Investigators must always know and adhere to agreed upon design elements, including patient inclusion criteria for enrollment, in clinical studies. Not adhering to these criteria may call the study into question. These rules must always be followed as a part of good clinical practice.
Registering clinical trials: Registration and results reporting of clinical trials in ClinicalTrials.gov is a is a new requirement under the FDA Amendments Act of 2007. More information can be found here. Pre-registration of clinical trials is also a condition of publication for some journals. In the case of sponsored research, the sponsor is responsible for registration or for designating the responsible party. Investigators should assure that their trial is being registered. Furthermore, information provided in the registration should be full, complete, and accurate. The International Committee of Medical Journal Editors (ICMJE) has produced information on clinical trials registration and publishing (3,4,5).
Use all grant and contract funds only for their intended purpose. Investigators must not use federal funds to perform research for a company with which they have a financial relationship (unless this is the explicit purpose of the mechanism used to fund the research, such as Small Business Innovation Research or Small Business Technology Transfer grants). Others who are involved with the company may not understand the constraints on grant recipients in academic institutions and may encourage or expect the diversion of funds to activities that benefit the company more directly.
When owning significant (using PHS/NSF definition) equity (stocks or options) in a company that is sponsoring research in your laboratory, understand that this poses unique challenges and risks for maintaining objectivity in research because it has a larger potential for financial gain than other forms of compensation.
Investigators should disclose the equity interest promptly and accurately so that the institution can monitor and manage them. Investigators holding supervisory roles in the university should pay special attention to risks because they may be responsible for the review and oversight of faculty members/investigators relationships with industry.