What is conflict of interest in research

Conflicts of interest can bias guideline recommendations to disproportionately favour new, expensive and less effective treatments and products. This is often to the detriment of both the public and the health systems on which they depend (Williams, Kevat et al. 2011). They can also promote over-diagnosis, over-treatment and lead to the medicalisation of normal human states and behaviours (Moynihan, Cooke et al. 2013). For example, dietary guidelines may be influenced by the conflicts of interest of companies, and of groups lobbying on their behalf, whose profits could be adversely affected by recommendations in the guidelines (Nestle 2013).

If a conflict of interest is not appropriately anticipated, recognised and managed it can bias guideline recommendations. If this bias comes to light it can discredit guidelines and cause serious reputational damage to guideline developers (Coyne 2007).

It is inevitable that most people involved in guideline development will have an interest or stake in the process—this is typically why they were selected to participate in the first place. A conflict of interest arises when there is a risk that their professional judgment or actions regarding a primary interest (i.e. the guideline) will be unduly influenced by a secondary interest (such as financial gain) (Institute of Medicine 2009).

Despite the simplicity of this definition, conflict of interest is a contentious and frequently misunderstood subject. Emerging evidence demonstrates that the understanding of conflict of interest has significantly deviated from its original meaning (Rodwin 2017)—that an individual would stand to directly or indirectly benefit from the recommendations of the guideline they are developing. The pervasiveness of financial conflicts of interests in guideline development (Bero 2017), which are by far the most damaging to guidelines, is being overshadowed by calls to report and exclude individuals based on non-financial interests (Lenzer 2016; Bero and Grundy 2018).

What is an interest?

As defined in the NHMRC Act 1992, interests are ‘any direct or indirect pecuniary or non-pecuniary interest’. Pecuniary (financial) interests are fundamentally problematic and can undermine confidence in a guideline. However, many non-financial interests are not considered problematic and could reasonably be viewed as essential components of character, personality and life experience (Bero and Grundy 2016). These can include:

• having published opinions on the effectiveness of a clinical, public or environmental health  intervention which is considered in a guideline
• publishing research that may be used in a guideline
• being an acknowledged expert or opinion leader on an intervention considered in a guideline
• having personal experience of a disease or condition considered in a guideline
• holding positions and convictions (political, intellectual, religious, ideological or other) relevant to the guideline.

Much of the current confusion comes from a misunderstanding that these sources of bias are conflicts of interest and therefore need to be managed. For example, there is a public perception that the personal interests of guideline development group members (such as lived experience, religious or political beliefs) may inappropriately influence decision making in guideline development. Similarly, members might be considered to be overly attached to a field of research, a particular clinical practice intervention, an ideological viewpoint or an intellectual position—this might give the impression that they cannot make objective and unbiased decisions.

While it is true that there is a risk of bias in these situations, they should not be confused with genuine conflicts of interest, which are primarily financial in nature (see Table 1 for examples). Bias from personal and intellectual interests is addressed by other means, such as reaching group consensus in decision making. A balance of different and even opposing personal and intellectual interests are precisely what you need to make sure your guideline development group can engage in healthy, informed discussion and debate on your guideline topic. The role of Chair is critical in these situations to steer the group through decision making processes in an impartial and transparent way (see Section 3).

Table 1. Types of conflicts of interest

NHMRC has published examples of interests that should be disclosed by individuals conducting research, participating in NHMRC peer review activities or seeking NHMRC Council or committee membership. You will note that none of these policies include disclosing interests such as religious beliefs, or having personal knowledge or experience of a disease or condition being considered in a guideline. This is not considered an interest for the purposes of determining conflicts of interest, or a valid or legal reason for excluding anyone from a guideline development group. While these interests might even be why you want to include an individual on the group, this information is defined as personal or sensitive information according to the Privacy Act 1988 and must be handled with careful consideration.

It is important for you to understand that having a conflict of interest does not in itself imply improper motivation or individual wrongdoing. Also, having a conflict does not necessarily preclude your involvement in a guideline development group. However, it is widely understood that conflicts can directly influence decision making in health care (Robertson, Rose et al. 2012; Dunn, Coiera et al. 2016) and this is often an unconscious act (Collins 2006; Cain and Detsky 2008). Because of this it is essential that all conflicts of interest are identified, transparently reported and appropriately managed to reduce the risk of bias. In particular, it is strongly encouraged that the risk of bias from financial conflicts of interest be eliminated by excluding individuals with these interests, particularly the Chair, from the guideline development group.

Sponsorship of the guideline development process by organisations or commercial entities is also considered a conflict of interest (Institute of Medicine 2009; Institute of Medicine 2011); however, this does not necessarily mean there is an issue with the guideline. The financial support provided by the funder, or the participation of a funding agency in guideline development (even as an observer) can have an influence on the working of a development group, which may bias a guideline.

While some mention of sponsorship conflicts of interest have been made in this module, ways to manage this and other sources of bias will be discussed in greater detail elsewhere (see the Project planning and Assessing risk of bias). This module primarily focuses on how to identify, report and manage conflicts of interest related to individual members of the guideline development group.

What to do

1. Develop a conflict of interest policy

Guideline developers should develop and operate under a conflict of interest policy that is understood and adhered to by everyone involved.

The key components of a conflict of interest policy are:

• identification of the scope of the conflict of interest policy and to whom it applies
• a process for disclosing interests (Section 5)
• guidelines for accepting sponsorship for the guideline development process
• a process for appointing chairs and development group members (Section 3 and Section 4)
• a process for identifying conflicts of interest (Section 2)
• a process for managing conflicts of interest (Section 6).

Interests which may contain personal or sensitive information must be managed in a way that is consistent with privacy and anti-discrimination legislation. For example, there must be no discrimination in the selection of guideline development members based on religion beliefs or health conditions.

Your policy should also include sanctions or penalties for dealing with circumstances where a member has failed to disclose interests that may impact guideline development. For example, if an individual has knowingly misled the group regarding their conflicts of interest, removal of the member from the guideline development group is necessary.

Examples of existing policies and disclosure forms are provided in Useful resources.

2. Determine if an interest is a conflict of interest

All guideline development group members must disclose interests relevant to the guideline topic. Group members must also be made aware of each other’s interests so that they can decide if a conflict of interest exists. This can be an item for discussion at your first developers meeting. Alternatively, a smaller working group of members can be assigned to review disclosures, identify conflicts and report back to the group for decision making. Some guideline developers even appoint dedicated conflict of interest advisors or legal teams to review their declarations.

There are many ways to determine whether an interest poses a conflict of interest. It may help you to consider the tips in Table 2 whenever interests are declared (Bero and Grundy 2016).

Table 2: Tips for making decisions about conflicts of interest (adapted from Bero and Grundy 2016)

If there is disagreement within your group about whether a conflict of interest exists, consider if the conflict of interest would ultimately stand up to public scrutiny (the ‘pub test’). You can also consult a group that is separate from the panel such as legal team. If there is a chance that it will reduce the trustworthiness of the guideline it might be prudent for you to take a more cautious approach—assume that a conflict of interest exists and manage it.

3. Appoint an independent chair

The chair’s primary qualification should be expertise in chairing and facilitating groups. The role of chair is critical as they are ultimately responsible for guiding your development group through the conflicts of interest policy. For this reason, it is strongly encouraged that the chair is independent, meaning they have no financial conflicts of interest and are free of non-financial interests as much as possible. The chair does not need to be an expert in the content area of your guideline; however, they should have a general understanding of the content to be able to participate in the discussion and deliberations (see the Guideline development group module). You should document and make public the process of how an unconflicted chair is recruited. It is prudent to appoint an independent chair prior to appointing other development group members. The chair can then assist you in the selection and screening of prospective members.

If you are unable to appoint a chair who is entirely free of non-financial conflicts of interest then the strategies employed to manage the chair’s conflicts must be documented and implemented at the start of each guideline development meeting. For example, you can nominate another member of the group who has no conflicts of interest in the relevant topic to act as chair for a particular discussion. The conflicted chair can withdraw from the meeting—they would therefore not be involved in drafting or approving any recommendations related to that discussion.

Co-chairs can be used where guidelines are likely to be complex or leadership is required to be shared amongst different disciplines (Institute of Medicine 2011). In this case, both co-chairs should aim to be free of conflicts of interest as described above.

You may be required to provide the chair with assistance when identifying and managing conflicts of interest of the guideline development group members. Some guideline developers even appoint dedicated conflict of interest advisors whose role is to advise and support the development group chair.

4. Select development group candidates

Selection of members for the guideline development group is described in greater detail in the Guideline development group module. When considering prospective candidates for your guideline development group, you should review their declarations of interests against the agreed conflict of interest policy.

While it is inevitable that many people under consideration will have interests because of their skills and expertise, you must avoid appointing members to the group if they possess serious conflicts of interest—for example, employees of pharmaceutical or device manufacturer companies, or people with a direct financial interest in the potential recommendations of the guideline.

It is strongly encouraged that your guideline development group will be composed of members with no financial or other links to relevant industry groups. If this is not possible then you should attempt to minimise the number of members who have financial or organisational conflicts so that they form a minority of members. Efforts to identify un-conflicted members should be documented.  Conflicted individuals must adhere to a strict conflict of interest management plan. This will ensure that they are not involved in any work where their interests can influence guideline recommendations. The management plan must be published in your final guideline for transparency.

5. Disclose interests throughout development

The business of guideline development groups should be conducted with all members of the group being aware of other members’ conflicts at all times. Because a member’s circumstances might change during development, a process for disclosing interests should be outlined in the group’s conflict of interest policy (Section 1).

A continuous disclosure process should include:

• a structured checklist of possible interests to be disclosed (e.g. financial ties or other affiliations through consulting, stock or shares, grants, honoraria, travel support, patents)
• an open-ended option to disclose any other interests not covered by the structured checklist
• the amount of each financial interest (which should not be limited by monetary thresholds)
• the timeframe of each interest (e.g. ongoing, current, or past—within 3–5 years).

Disclosure of interests is an ongoing process. Members must update their disclosures and advise fellow group members of any changes as they arise. The updated disclosures, any conflicts of interest and a description of how they were managed must be published in the final guideline. It is also good practice to make the disclosure of new interests a standing agenda item at your guideline development group meetings. This will allow for regular group discussion of potential conflicts.

6. Manage conflicts of interest

If you have determined that a guideline development group member has a conflict of interest there are ways to manage the situation. This will ensure that the process is as transparent as possible and that any risk of bias is minimised. These methods should be described in detail in your group’s conflicts of interest policy (Section 1). Some options include:

• a conflicted member being present but not taking part in any discussions or decision making related to the specific area or issue
• a conflicted member recusing themselves from a meeting when a decision or recommendation is made related to the conflict of interest
• excluding a conflicted member from involvement in the writing or approval of recommendations associated with the conflict
• removing a conflicted member from the guideline development group for failure to disclose major conflicts of interest (this may also require re-evaluating the evidence or guideline recommendations depending on the stage of guideline development)
• a conflicted member eliminating potential conflicts of interest during the duration of guideline development (such as leave of absence from board positions)
• disallowing input from sponsoring organisations in guideline development
• ensuring that any decision to exclude members from discussion and decision making is made in full consultation with all members of the group and/or the independent assessors of the interests (such as a conflict of interest advisor or legal team)
• recording all decisions in the final guideline or publicly-accessible administrative reports associated with the guideline.

7. Publish declarations of interest in the guideline

Your final guideline (either in the guideline itself or in the administrative reports published alongside the guideline) must include a statement for each guideline development group member declaring their interests related to the guideline topic, noting whether they had conflicts of interest or not. The information you publish must describe what the conflicts were and the strategy used to manage each of them. It is essential that the whole process is transparent and publicly accessible. It is also strongly recommended that you include this information when your guideline and any administrative reports are released for public consultation.

NHMRC requirements

Guidelines approved by NHMRC must meet all requirements outlined in the Procedures and requirements for meeting the NHMRC standard. The following requirements apply to the Identifying and managing conflicts of interest module:

• A.1 The organisation/s responsible for developing and publishing the guideline is/are named.
• A.2 Sources of funding for guideline development, publication and dissemination are stated.
• A.3 A multidisciplinary group that includes end-users, relevant disciplines and clinical experts is convened to develop the purposes, scope and content of the guideline, and the process and criteria for selecting member are described.
• A.4 Consumers participate in the guideline development, and the processes employed to recruit, involve and support consumer participants are described.
• A.5 A complete list of all the people involved in the guideline development process is provided, including the following information for each person: name, profession or discipline, organisational affiliation and role in the guideline development process.
• A.6 Potential competing interests are identified, managed and documented, and a competing interest declaration is completed by each member of the guideline development group.
• A.7 A list of organisations formally endorsing the guideline is provided.

Additionally, subsection 29(1) of the Public Governance, Performance and Accountability Act 2013 requires that:

“An official of a Commonwealth entity who has a material personal interest that relates to the affairs of the entity must disclose details of the interest.”

If the NHMRC or other Commonwealth entity were to appoint a committee to develop a guideline under their legislation, and where under their legislation a committee member is an official for the purposes of the PGPA Act, appointed members of the committee would be legally required to disclose details of the interest not just in relation to the scope of the guideline, but in relation to the affairs or activities of the Commonwealth entity. Further information on the scope of this provision is provided in the Finance Resource Management Guide No 203 available at: http://www.finance.gov.au/government/managing-commonwealth-resources/general-duties-officials-rmg-203.

NHMRC Standards

The following Standards apply to the Identifying and managing conflicts of interest module:

2. To be transparent guidelines will make publicly available:

  2.3 The declarations of interest of members of the guideline development group and information on how any conflicts of interest were managed

  2.4 All sources of funding for the guideline.

4. To identify and manage conflicts of interest guideline developers will:

  4.1. Require all interests of all guideline development group members to be declared

  4.2. Establish a process for determining if a declared interest represents a conflict of interest, and how a conflict of interest will be managed.

Useful resources

Developing NICE guidelines: the manual (2014) – 3.6 Code of conduct and declaration of interests

Cochrane Collaboration disclosure of potential conflicts of interest information

Examples of existing declaration of interests policies:

Policy on the Disclosure of Interests Requirements for Prospective and Appointed NHMRC Committee Members

2014 UK National Institute for Health and Care Excellence (NICE) Policy on Conflicts of Interest (currently under review)

2015 Guidelines International Network: Principles for Disclosure of Interests and Management of Conflicts in Guidelines

World Health Organization (WHO) Handbook for Guideline Development: Chapter 6 - Declaration and management of interests

National COVID-19 Clinical Evidence Taskforce Conflict of interest policy and Declaration of interest policy

References

Bero, L. (2017). Addressing bias and conflict of interest among biomedical researchers. JAMA 317(17): 1723-1724.

Bero, L. and Q. Grundy (2018). Not all influences on science are conflicts of interest. American Journal of Public Health Editorials (Forthcoming 2018).

Bero, L. A. and Q. Grundy (2016). Why Having a (Nonfinancial) Interest Is Not a Conflict of Interest. PLoS Biology 14(12): e2001221.

Cain, D. M. and A. S. Detsky (2008). Everyone's a little bit biased (even physicians). Journal of the American Medical Association 299(24): 2893-2895.

Collins, J. (2006). Professionalism and physician interactions with industry. Journal of the American College of Radiology 3(5): 325-332.

Coyne, D. W. (2007). Influence of industry on renal guideline development. Clinical Journal of the American Society of Nephrology 2(1): 3-7; discussion 13-14.

Dunn, A. G., E. Coiera, et al. (2016). Conflict of interest disclosure in biomedical research: A review of current practices, biases, and the role of public registries in improving transparency. Research Integrity and Peer Review 1.

Institute of Medicine (2009). Conflict of Interest in Medical Research, Education, and Practice, National Academies Press.

Institute of Medicine (2011). Clinical Practice Guidelines We Can Trust. Committee on Standards for Developing Trustworthy Clinical Practice Guidelines, National Academies Press.

Lenzer, J. (2016). When is a point of view a conflict of interest? British Medical Journal 355.

Moynihan, R. and L. Bero (2017). Toward a Healthier Patient Voice. More Independence, Less Industry Funding. Journal of the American Medical Association Internal Medicine.

Moynihan, R. N., G. P. Cooke, et al. (2013). Expanding disease definitions in guidelines and expert panel ties to industry: a cross-sectional study of common conditions in the United States. PLoS Medicine 10(8): e1001500.

Nestle, M. (2013). Food politics: How the food industry influences nutrition and health.

Robertson, C., S. Rose, et al. (2012). Effect of financial relationships on the behaviours of health care professionals: a review of the evidence. Journal of Law, Medicine and Ethics 40(3): 452-466.

Rodwin, M. A. (2017) Attempts to redefine conflicts of interest. Accountability in Research - Policies and Quality Assurance, 1-12 DOI: 10.1080/08989621.2017.1405728.

Rose, S. L., J. Highland, et al. (2017). Patient Advocacy Organizations, Industry Funding, and Conflicts of Interest. Journal of the American Medical Association Internal Medicine.

The Royal Australasian College of Physicians (RACP) (2006). Guidelines for ethical relationships between physicians and industry, Third Edition.

Williams, M. J., D. A. Kevat, et al. (2011). Conflict of interest guidelines for clinical guidelines. The Medical Journal of Australia 195(8): 442-445.