Conflict of interest guidelines for clinical guidelines

Governments have a compelling interest in guidelines that represent only evidence-based research, unaffected by competing interests. Underresourced health authorities must have confidence that appropriate medications and practices are recommended. The inclusion of more expensive but less efficacious medications can incur significant cost because of the exponential gearing effect that guidelines may have. For example, Eli Lilly sparked a controversy by funding the development of “Surviving sepsis” guidelines while conducting a sophisticated campaign for clinicians to advocate for greater access to activated protein C in treatment, and while having financial ties with a number of guideline authors.7

A COI occurs when “a set of conditions in which professional judgment concerning a primary interest (such as a patient’s welfare or the validity of research) tends [or has the potential] to be unduly influenced by a secondary interest (such as financial gain)”.8 COIs can arise through the acts of individuals, institutions and professional bodies; the most common are authors having financial links with industry, including being paid consultancies or honoraria, or holding company shares. EDITConscious, wilful manipulation of guideline content is likely to be rare; undeclared and poorly managed conflicts are likely to be more common.

Both financial and non-financial conflicts are problematic. Non-financial conflicts may include serving as a board member or having a spouse in the employ of a pharmaceutical company. The Lancet’s statements on COIs are lucid and practical. The journal refuses to publish authors who:

In summary: “Is there anything ... that would embarrass you if it were to emerge after publication and you had not declared it?”10

Effective management of conflicts depends on individual attributes (such as self-awareness) and institutional management processes. Conflicts may have an institutional source if significant corporate funding is received and staff participate in related guideline development. Good practices are particularly necessary to manage institutional conflicts, as individuals in those instances may be less likely to perceive or declare a conflict.

Guidelines are valuable and vulnerable. Our review of the country’s most prolific guideline developers shows that only 15% of guidelines have COI statements (Box 1). This raises questions about whether medical bodies are affected by unrecognised, and thus unaddressed, extraneous interests, and may erode the trust the community has in the profession11 to speak authoritatively about health problems.

A recent study of 313 Australian clinical guidelines used between 2003 and 2007 found that almost 80% had no competing interest statement.12 This lack of disclosure is inexplicably inconsistent with practices adopted by peer-reviewed journals and with guidelines for participation in meetings of some medical organisations.13 Rates of conflict disclosure on guidelines are so low that, at best, they may indicate that the profession is in a “precontemplative” phase, oblivious to the existence or extent of the issue.

We were unable to quantify total sponsorship from pharmaceutical companies to guideline-developing bodies as institutions and to individuals on guideline-drafting panels. While organisations often disclose corporate supporters on their websites, information on how much is donated and where it is directed is neither easily accessible nor comprehensive. In some cases, the websites of pharmaceutical companies are more informative than developers’ websites. For example, Pfizer Australia declares on its website a donation of $150 000 in 2010 towards the Heart Foundation’s Career Development Fellowship.14 However, there is no corresponding statement on the Heart Foundation website or in its annual reports.15 One must consult the 2011 Fellowship Application Guide to learn that “Funds may be available from member companies of the Heart Foundation Pharmaceutical Roundtable to support several Research Awards each year”.16 The Guide lists the corporations that constitute the Roundtable, including Pfizer, but does not specify the amount Pfizer provides.17 Pharmaceutical sponsorship of medical research and professional bodies is considerable, raising the spectre of influence, which should be unequivocally confronted by the profession.18

Developing sound processes

It is insufficient for developers to claim to have internal processes for conflict management, which they do not outline. The benefit of having a published COI statement is that it allows medical and non-medical audiences to consider biases developers may have, and seek other evidence when warranted. We propose a six-step process (Box 2) to improve the transparency of guideline development. We further propose that guideline developers should publicly outline the processes by which they manage conflicts. Conflict statements for guidelines should inform the reader about the nature of competing interests and how they were managed.

Developers of guidelines may adopt a number of strategies, including the following:

• A period of 3 years from when industry assistance was last received may be regarded as sufficient time for the conflict to have lost its potential for “undue influence” and allow researchers to resume their places on drafting committees (with all past benefits still being declared).

• The structure of drafting panels could be tiered, and those with a competing interest would only discuss or draft certain sections of the guidelines (eg, sections relating to the nature of the disease), while those without a competing interest might be responsible for writing sections on treatments.

• Some researchers may contribute to guidelines at early stages with the final product prepared by those without competing interests, as rigorous processes to manage conflicts may restrict the participation of prominent figures with extensive links to industry.18

• The committee chair may be an individual who has not received industry benefits and could have the final decision on recommendations concerning treatment options.

In the United States, the National Institutes of Health (NIH) have detailed and instructive rules to manage COIs for employees (Box 3). The suggestion that conflict management processes be public is an additional requirement.

There may be some advantage if independent, statutory bodies produce future guidelines20 and other groups cease independent guideline development. In the United Kingdom, the National Institute for Health and Clinical Excellence (NICE) is part of the National Health Service and is the main body for clinical guideline development. The Australian Commission on Safety and Quality in Health Care or the NHMRC National Institute of Clinical Studies could assume a similar role, though this would require government funding. This seems unlikely given the current outsourced model that — despite its flaws — costs the government little.

Placing statutory bodies in charge of guideline development may prevent institutional-level conflicts, but not those of individual panel members. NICE has a policy encompassing many types of financial and non-financial interests.21 The policy provides that committee heads with financial conflicts should not take part in guideline development.22 The COIs are recorded in minutes that are accessible on the internet, and a COI register is accessible on request. An increasing number of conflict statements are now included in the guidelines themselves.

The NHMRC key principles for developing guidelines do not mention the management of COIs.23 The NHMRC standards and procedures for externally developed guidelines refers to the issue, asking that drafting groups disclose their COIs, but is silent on the need to publicly disclose conflicts and how they are managed.24 The NHMRC must urgently promote a more ethically sound development process for guidelines. It should be a condition of NHMRC guideline approval that competing interest declarations and processes are made public. This would be consistent with the NHMRC’s rigorous process of conflict management in the evaluation of research grant applications — it is no lesser cause nor fewer dollars that are at stake in the development of clinical guidelines.

Finally, although the pendulum must swing towards greater transparency, this must be balanced against the risk that overly onerous obligations become a disincentive to participation in guideline development. It is important to establish a culture of disclosure and sound management of conflicts rather than attempting to implement a standard that cannot be met. As Tim Kendall of NICE has said, “It’s hard to find clinicians for guidelines who don’t have some COIs. We think it’s important that the guideline process is open and transparent”.25