Therapeutic Guidelines Limited is a not-for-profit company. Its reputation is staked not only on its publications, but also on its independence of government and pharmaceutical interests. It is financially self-sufficient and does not receive any form of government or industry funding. This is a very satisfactory position to be in, both intellectually and administratively, but it also means that Therapeutic Guidelines needs to carefully manage its resources, relationships with other organisations and the clinical community, and the decisions it makes about the use of its products.

Therapeutic Guidelines evolved out of activities dating back to the 1970s, when a group of health professionals formed to develop antibiotic guidelines in response to the worrying and emerging problem of antibiotic resistance. The guidelines are now widely respected and are an accepted part of the Australian medical culture. They are characterised by their comprehensiveness, authority, convenience, currency and reputation for being a trustworthy source of independent therapeutic advice.

The Therapeutic Guidelines collection currently includes around 3000 topics, which are regularly revised and published. Experts work in multidisciplinary groups to consider feedback, assess and evaluate the evidence and develop the content. The finalised content is reviewed by external experts if required, endorsed by professional organisations and vetted through internal quality control processes.

The Therapeutic Guidelines website provides detailed information about the history and activities of Therapeutic Guidelines, including a description of the process used to develop the content, and our activities to support the quality use of medicines in developing countries.

Preparing guidelines is a complex process involving a large number of players. There are several areas where independence and bias need to be considered, and several factors that can threaten the reliability of the advice Therapeutic Guidelines provides. Every step needs careful thought and planning to maintain the integrity of the process. In some areas, such as managing conflict of interest, Therapeutic Guidelines can institute measures that allow it to control the integrity of the process. In other areas, such as the limitations of the available evidence, Therapeutic Guidelines has much less control.

Reliable research is an integral component of Therapeutic Guidelines. To ensure that the evidence is appropriately assessed, Therapeutic Guidelines works with people who have both critical appraisal skills and the relevant clinical experience to provide guidance about the treatments most likely to be beneficial and least likely to cause harm to patients.

The issue of conflict of interest has been the focus of much discussion in the guideline community and in other contexts and a number of organisations have developed conflict of interest policies as a result. For example, to develop the American Thoracic Society’s Official Policy Statement on the management of conflicts of interest1 , Schünemann and colleagues used existing reviews of policies that were prepared for the World Health Organization (WHO) and for an American Thoracic Society guideline methodology workshop as their evidence base. They also looked at the policies of selected organisations (American College of Physicians, American College of Chest Physicians, American Medical Association, Society of Critical Care Medicine, International Committee of Medical Journal Editors, and WHO). The resulting American Thoracic Society Policy Statement provides the following, particularly helpful definition:

Conflict of interest is defined as a divergence between an individual’s private interests and his/her professional obligations such that an independent observer might reasonably question whether the individual’s professional actions or decisions are motivated by personal gain, such as financial, academic advancement, clinical revenue streams, or community standing.

So, how well is conflict of interest managed in clinical practice guidelines? Research over the last 10 years shows that many guidelines do not disclose author conflict of interest statements:

  • 79% in a study of 313 Australian guidelines (2009)
  • 58% in 215 guidelines involving drugs on the National Guideline Clearinghouse (2004)
  • 95% in 44 guidelines endorsed by North American and European societies (2002).

However, the landscape is gradually changing. The need to declare and publish conflicts of interest is now more widely accepted, and current thinking is that robust mechanisms are needed to help manage people’s declared conflicts. Many organisations have published advice in this area, but the US Institute of Medicine2 and the Guidelines International Network3 statements are particularly useful. 

In 2008, the Institute of Medicine was directed by the US Congress to develop standards for the development of rigorous, trustworthy clinical practice guidelines. This was prompted by concerns from clinicians, methodologists and consumer groups about the quality of guideline development processes and the resulting questionable validity of guideline recommendations and guideline-based performance measures. Three years later, the Institute published a 266 page report that contained eight proposed standards covering all the elements considered to be essential to developing sound guidelines.2

The Institute of Medicine report proposes the following strategies for managing conflicts of interest:

  1. Written disclosure of current and planned, commercial and noncommercial, intellectual, institutional, and patient–public activities pertinent to the scope of the guidelines before appointment.
  2. Each expert group member to report and discuss all conflicts of interest with the group and explain how their conflict of interest could influence the development process or specific recommendations before starting the work.
  3. Members to divest themselves of financial interests they or their family members have, and not participate in marketing activities or advisory boards of entities whose interests could be affected by the recommendations.
  4. Whenever possible, expert group members should not have conflicts of interest.
  5. In circumstances where expert groups are not able to perform their work without members who have conflicts of interest, such members should represent not more than a minority of the expert group.
  6. The Chair or Co-Chairs should not have conflicts of interest.
  7. Funders should have no role in the development process.

In response to concerns about the feasibility of implementing such a long list of criteria, Guidelines International Network developed a more succinct seven page document that proposes a minimum set of international standards for developing trustworthy guidelines.3

Both sets of standards emphasise the need for strategies to actively and transparently manage conflicts of interest.

Therapeutic Guidelines Limited’s conflict of interest policy

The pharmaceutical industry and government both rely heavily on bodies outside their own spheres, such as universities and hospitals, for product development and regulation. In this context, given their experience and expertise, it is likely that Therapeutic Guidelines directors and members of expert groups have, or have had, some association with the pharmaceutical industry and government committees.

To minimise the possibility of inappropriate influences, Therapeutic Guidelines has included the following strategies in its conflict of interest policy:

  • Expert group members are asked to declare any potential conflicts of interest before being appointed. • Once appointed, a register of declared interests is maintained, circulated and updated at every expert group meeting.
  • All expert group meetings are chaired by Therapeutic Guidelines’ Medical Advisor, who has no conflicts of interest that could, or could be perceived to, erode the integrity of the guidelines.
  • The Chair decides how to manage declared interests and discusses these with expert group members.
  • Information about expert group members’ declarations of interest and how these were managed are published when the guidelines are released.

The conflict of interest policy for the Board of Therapeutic Guidelines and all members of its guideline teams is available on the website. This new policy was updated in 2012 to ensure that declared conflicts of interest are also published online. It is being implemented prospectively as each guideline is updated and new expert groups are established and provide their consent.

To conclude, one of the key objectives for this forum is to consider best practice regarding the management of conflicts of interest and to identify whether there is anything further that Therapeutic Guidelines should do to manage potential sources of bias when developing its guidelines.

Equally important is the need to focus on the issue of bias in the research literature and evidence base, and to consider whether new sources of funding and regulatory changes are needed to improve the scope and design of clinical trials.