Therapeutic independence and evidence-based medicine

Panel members 

Professor Rachelle Buchbinder

Professor Terry Campbell

Professor Silvio Garattini

Associate Professor David Menkes

Assistant Professor Barbara Mintzes

Dr Philipa Rothfield

Associate Professor Ian Scott

Moderator

Professor Paul Komesaroff

Each panellist was invited to comment on the issues raised by Professor Silvio Garattini and Assistant Professor Barbara Mintzes in their earlier presentations, and comments from the forum participants were also invited.

To what extent are there sufficient mechanisms to discern between biased and independent data?

In the area of psychiatric medicine there has been considerable concern about the influence of commercial interests on the data used to register new medications, especially for ‘atypical’ (second- and third-generation) antipsychotics, as well as selective serotonin reuptake inhibitors and related antidepressants.

There are also widespread concerns about the lack of follow-up data on the long-term effects of newly registered therapeutic products. Regulators need to have ways to follow up effectiveness and safety data on a routine basis. Some of the mechanisms for assessing the quality of the data include consideration of the comparative effectiveness of the new drugs, but often this information is not available because of the trial design used, deficient ascertainment and incomplete reporting.

Does the process used to allocate research grants and funding naturally encourage researchers to ‘talk up’ their study and the results?

There is considerable support for finding ways to fund investigator-initiated trials. Full disclosure of all drug company links and funding should be required. Fines and other penalties should be imposed if drug companies falsify data. Some of the fines could be used to fund investigator-initiated trials.

There are persisting issues of real and perceived conflicts of interest. Some people will not be able to easily identify whether they have conflicts, or will have interests they are not aware of (e.g. they may not know where their university gets its funding sources). People funded by government may also be influenced by the government's current policy imperatives. These issues, including definitions of ‘independence’, are often complex.

There is a need to ensure that guideline development groups include wide representation from different health disciplines and people with different backgrounds and skills, and it should be clear where there are contrasts between sets of norms, values and ideals. This will allow members of guideline development groups and committees to get a wider picture of each contributor’s influences.

The issue of conflict of interest is not a solely medical/health issue. For example, it is important that all influences and interests are known when members of a jury are selected. Directors and businesses also have formalised processes for declaring and managing conflicts. People submitting journal articles are also required to make declarations in accordance with the statements on conflicts of interest in medical journals by the World Association of Medical Editors and the International Committee of Medical Journal Editors. Medical journals need to be checked to ensure they follow their own code of ethics and actively enforce their policies with contributors.

There is a need to educate clinicians and consumers in critical appraisal of intervention studies and other types of studies, in part to enable awareness of the pervasive risk of bias from diverse sources.

There are opportunities for guideline developers such as Therapeutic Guidelines in Australia to identify areas where further research is needed to fully cover the spectrum of information required in each therapeutic area. There could also be opportunities for guideline developers to have a role in setting the research agenda and in actively promoting changes in healthcare practice.

Is there a need to reinforce the critical capacities of the people on ethics committees? Do the ethics committees and researchers actively work within the framework of ethical principles for medical research described in the Helsinki Declaration?

Ethics committees have the ability to change or seek modifications to protocols or the design of studies they are considering. However, this can be difficult, especially when multicentre approvals are being considered. There was discussion about whether the ethics committees could introduce a process of independent scientific review of study design before considering proposals. NPS MedicineWise has recently been working with ethics committees to help them access high quality information about medications. There are also plans to change the structure of ethics committees around Australia. This might include the opportunity to provide training and information to committee members to ensure they understand issues associated with study design and the need for transparency and independence.

The problem of overdiagnosis must be addressed by guideline developers. The British Medical Journal¹ and the Cochrane Collaboration are actively discussing and debating the growth of new diseases and the medicalisation of normal human development and ageing being promoted by the pharmaceutical industry and other vested interests.

The influence of consumers is seen as vital in all parts of the guideline development process. If there is going to be real change, it is important to recognise that patients and consumers are at the heart of the system and that they matter the most. Consumers must be given credit for being able to understand and digest information about their health. They want to know what treatments are going to do, how they work, how long they will take to work and what the risks and benefits are.

The Cochrane Colloquium works actively and effectively with consumers. It is useful to involve consumers in the design of every trial so that researchers and funders know that the right questions are being asked. For example, in the area of musculoskeletal medicine many consumers want to know basic information that will help them in their daily lives, such as ‘what is the best kind of mattress to help reduce or manage back pain?’, but this topic is not well covered by research.

The important issue is how to improve the quality of science and to take the focus away from the product and instead to focus on the needs of the person.

How can we introduce greater transparency into the data relating to drugs? Who should be the agent for change? Who are the critical players/partners/stakeholders to lead the call for change? What are the preconditions for change? What are the barriers to introducing these changes?

The government has some awareness of these issues and has recently established a website for registering clinical trials (www.anzctr.org.au). At this stage there is no requirement to publish the results of all registered trials.

There are three main areas where change is needed:

1. Regulators should make publicly available all of the information they have access to when approving a drug.
   
2. Regulators should require applicants seeking approval for their drugs to demonstrate that the new drug has a proven therapeutic benefit compared to existing treatments.
   
3. Governments should take steps to increase the number of investigator-driven clinical trials.
   

Is there a wider role for Therapeutic Guidelines in progressing these discussions? For example:

• Would it be possible for Therapeutic Guidelines to take a leadership role in establishing gold standards of behaviour and good governance in clinical research and to provide advice to other Australian guideline developers on ways to manage conflicts of interest?
  
• Is there a wider global role for Therapeutic Guidelines and its products?
  
• Can Therapeutic Guidelines extend its purely scientific approach to include wider contextual issues such as social determinants?
  
• Can Therapeutic Guidelines take on a role promoting a wider understanding of the value of guidelines and also teaching critical appraisal skills?
  
• Does Therapeutic Guidelines have a role in improving the uptake of guidelines?
  
• Can Therapeutic Guidelines begin to develop guidelines that address comorbidities?