Conflict of interest (COI)
when an individual has interests in the outcome of the research that may lead to a personal advantage and that might, therefore, in actuality or appearance compromise the integrity of the research or investigator’s judgment in conducting or reporting research
COIs can stem in a variety of ways in biomedical research.
- The potential sources of bias start from the study design and its conduct
- to conclusions made out of the research and subsequently its publication.
- protocol violations may go unreported, contributing to a flawed outcome.
- Researchers à selective in reporting research outcomes or analyses, which is a well-documented source of bias.
- Evidence also shows that studies with an underlying financial COI, tend to publish research outcomes that favor the financial interest.
TYPES OF COI
COI in clinical research may be classified as financial or non-financial and can take place at the level of
- Principal Investigator (PI),
- Ethics Committee (EC) members,
- Institutions or Sponsors
At the level of a PI,
- an underlying financial COI could potentially influence his/her professional decisions.
- certain adverse events (AEs) during a study may be chosen, to be under-reported by the PI.
- This motive may, in turn, save the sponsor from paying compensation
- However, such a move may prove detrimental to patient care and later endanger public health.
- non-financial COIs involving PI can be academic where he/she desires for prestige, power and professional advancement or has an interest in obtaining positive results in order to obtain publications.
- PI may also have a personal COI by way of preferring family and friends for a particular treatment such as in an unblinded study in a desire to alleviate pain and suffering.
- may similarly be involved in financial gain and may have an inclination towards approval of industry-sponsored studies.
- personal preference may result in biased decisions of EC members towards studies submitted by family and friends
- by way of favoring a pharmaceutical company to receive financial support for research may imply a financial COI.
- An institution may also be involved in non-financial COI for political reasons.
- Further, when an institution conducts a CME, acceptance of funding from the industry may bias the topic chosen for the CME event, in favor of the interests of the industry rather than the institution’s own mission.
- Such COIs may also lead to bias by the institution or organization while developing a guideline and advocating treatments to patients.
Sponsors often have underlying COIs as they can profoundly influence study designs, analysis, and interpretation of data. Further, they may also tend to suppress a negative result or AEs.
COIS IN INDIA
- One major instance of COI in India was the highly publicized clinical trial on the Human Papillomavirus (HPV) vaccine that was carried out in India in 2009.
- This trial was a collaboration between USA based organization PATH (Program for Appropriate Technology in Health) and ICMR.
- The trial drew much attention after several serious adverse events such as convulsions and death of numerous children were reported.
- It was later reported by India’s Parliamentary Standing Committee on Health and Family Welfare that this trial had some major COIs.
- Firstly, the ICMR, which was to formulate ethical guidelines for researchers were found to be directly involved in the advisory committee of the project.
- Secondly, manufacturers had earlier provided financial support to conduct the vaccine trial in the Department of Obstetrics and Gynecology, All India Institute of Medical Sciences (AIIMS), whose Head of Department was later appointed as a member of the enquiry committee.
- This was a clear instance of COI as her findings could not be relied upon. There were several other lapses reported such as non-disclosure of an international trip of the same individual, sponsored by the manufacturer, under the Foreign Contribution Regulation Act (FCRA).
- the trial was subsequently stopped
DISCLOSURE OF COI
- Currently, the requirement for authors to disclose the list of companies that provide funding support for their studies, while applying for publication, is greater than ever before.
- The importance of disclosure of COI lies in the fact that readers, reviewers, and editors are allowed to assess for themselves, potential biases and their impact on the validity of the results and conclusions of any study.
- However, this does not imply the resolution or elimination of a COI.
SHOULD PATIENTS BE INFORMED OF COI?
- In order to market a new drug or device, a pharmaceutical company often provides gifts, royalties or consultant payments to the clinician.
- Such financial interests may prompt a clinician to subconsciously change his/ her behavior towards the patient.
- This would likely be pertaining to the cost of health care rather than patient clinical outcomes.
- For the patient to understand and be fully aware of such conflicts, better methods need to be implemented.
- These may include a one-on-one dialogue with the physician or reaching out to an institutional or public domain, which provides information on financial disclosures and their implications for example, on a medical center website.
- Such websites may help a patient to access and process the information at his/her own pace and convenience.
GUIDELINES FOR COI IN INDIA
- The Indian Good Clinical Practice (GCP) guidelines, emphasizes the need for identifying COI between scientific responsibilities and possible business interests of researchers
- The latest ICMR guidelines, revised in 2017, suggest recommendations for research institutions, researchers and ECs to help identify and manage COIs in research. However, a clear outline of what constitutes a COI is lacking.
- research institutions should develop and implement policies and Standard operating procedures (SOPs) to address COI issuesà
- educate their staff about such policiesà
- monitor the research for accuracy and objectivity and advise à
- not to interfere in the functioning and decision making of the EC.
- Researchers are advised to ensure that documents submitted to the EC include disclosure of COI (financial or nonfinancial) that may affect their research
- IECs on the other hand, are suggested to evaluate each study based on any disclosed COI and ensure that appropriate action is taken to mitigate this and
- recommends that their members should also disclose their own COI and take appropriate measures to recuse themselves from reviewing or decision making on protocols related to their COI and make appropriate suggestions for management, if COI is detected at the institutional or researchers level.
- Financial and non-financial COIs are often treated the same way. However, their implications remain different.
- Some non-financial COIs may be associated with ethical and privacy issues and may affect disclosure. For example, in certain studies like abortion-related health outcomes or same-sex transmission of disease, it may be difficult to disclose the researchers’ own experience with abortion or their sexual affiliation respectively.
- When a COI disclosure reveals a potential, perceived or actual COI, a management strategy should be developed to document and proactively address the issue.
- In some circumstances, simply the act of declaring the conflict may be sufficient to adequately mitigate or manage it.
- Other strategies à consideration of removal from situation or conflict or restricting the access of the person to relevant information that is sensitive or confidential and
- recruitment of an independent third party to oversee part or all of the process which can be applied to the level of PI, EC, and Institution.
- when a member of the IEC is himself/herself in a clear COI, during the review of his/her own research project(s). In such instances, the member must be refrained from being present during the particular project’s review.
- Occasionally, the parent organization might have a strong interest in bringing a project to fruition. In such cases, it is important for the IEC to act independently from the parent organization and institutions must respect the autonomy of the IEC
- institutions to have policies for declaring and managing COIs that should be percolated to all stakeholders (investigators, IEC members, sponsors, authors, and editors) through workshops organized by central agencies drawing examples from real-life scenarios.