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In recent years, economic rationalism has forced public institutions to look for non-governmental sources of income and links with industry.¹

Our dermatology department needed equipment for which funds were not available from the hospital budget, but would be available from payment for participating in a drug trial. The trial sponsors wished to compare their product with the current "best" cream and a placebo in a randomised controlled trial. Participation would be voluntary, the risk of harm minimal, privacy would be protected and patients would be "suitably informed".

An administrative and financial agreement was arranged between our department and the professional contract research organisation responsible for the study. Details of this trial are shown in the Box. There was some pressure for quick approval, as doctors working from their private rooms had an impressive head start and were already entering patients in the trial. Our institutional ethics committee sought a number of changes to the trial protocol, but it was eventually approved. We had no sooner entered patients into the trial than it was closed: the required number of patients had been supplied by private practitioners. Was this a case of a public institution being too slow in responding to the demands of industry?

Perhaps, but there were other, more important issues, particularly those relating to restrictions of intellectual property, the opportunities for publication bias and informed consent of patients in clinical trials.

Intellectual property

The rights to the information gathered by the drug trial were legally under the control of the contract research organisation. It is likely that many patients enter drug trials believing that the resulting knowledge will be available for the common good. Would the public readily enter similar trials if they knew the intellectual property was controlled by the sponsors and may not be available for the public record? Commercial sensitivity, the complexity of running multicentre trials and timing of publication demand some flexibility, but an insistence on public record of all trial results should be non-negotiable.

Publication bias has consequences

My concerns about publication bias are shared by others,^2,3 and are as follows:

• If the findings remain the property of the sponsor, then how much evidence is never reported?

• How truthful is medical evidence that relies on publications selected by an industry which needs to sell new drugs or variations on existing drugs ("me-too" drugs)? "Me-too" drugs require clinical trials showing some advantage, and these trials may be designed with marketing strategies as the driving hypothesis. Trials that show no difference or no effect, or even adverse effects, are less likely to be published, while positive results are likely to be published and promoted. Pharmaceutical companies have to make a profit or they fail.⁴ There is evidence for selective publication of drug trial information,⁵ and even manipulation of information⁶ and opinion.^7,8

• Publication bias may result in unsafe or more expensive therapies being used. Health resources are limited and inefficient use results in rationing elsewhere. We need all available information to be on the public record to inform us in clinical decision-making.

Financial disclosure as part of informed consent

Recent judgments in the Australian justice system suggest that informed consent should involve disclosing all issues that might be significant to the patient making the decision.⁹

Patients may enter drug trials as part of an ongoing doctor-patient relationship, and this may make them feel more secure in the rigours and supervision imposed by trial conditions.¹⁰ Patients' trust in doctors is based on the belief that it is their health that remains the central focus. Full disclosure of financial interests might disturb this trust, particularly in trials conducted in private clinics with financial payment made directly to the medical investigator. In public institutions money gained from trials is not usually paid directly to doctors. Generally, most of it is spent on acquiring necessary equipment or to support further research — something likely to be supported by the public. Disclosing trial financial details to patients will create additional difficulties, but truth is more important than false trust.

The Royal Australasian College of Physicians' Ethical guidelines in the relationship between physicians and the pharmaceutical industry¹¹ and the National Health and Medical Research Council's National statement on ethical conduct in research involving humans¹² state that there should be disclosure to research participants of relevant aspects of the budget. More recently, financial disclosure in clinical trials has come under scrutiny in the media.^13,14 If we don't ensure such disclosure, then either the political or judicial system might impose it on us.

Suggested requirements for drug trials

We have progressed a long way in the ethical review of research. However, ethics committees also have increasing workloads and diminishing budgets. They are not necessarily equipped to obsessively interrogate and supervise all submitted projects.^15,16

I propose that trial submission forms to ethics committees have two or three further questions confirming a commitment to publish trial results¹⁷ and to disclose financial details. This would flag this requirement to both researchers and the industry. Some ethics committees may already have these requirements. The resulting transparency would increase public trust in clinical trials, which, in turn, might make patients more likely to volunteer, ensuring wide and valid representation of different trial subjects.

Is trial information reward enough for the public?

In entering drug trials the public are risking more than the pharmaceutical industries and the investigators. We all agree that clinical trials are necessary and that, in the right setting, they provide information on new and effective therapies. However, there are other rewards that could be offered to the public.

Ready public availability of information on the risks of pharmaceutical products would be an appropriate reward. It is estimated that 80 000 Australians are admitted yearly to Australian hospitals with adverse reactions to pharmaceutical products.¹⁸ A proportion of drug trial monies could be dedicated to the study and education of adverse drug reactions. Another proportion of drug trial monies could be dedicated to funding a trial register site¹⁷ to provide abstracts of all clinical trials and their results.

Finally, we need to examine how and by whom clinical trials are conducted as they are taken from academic medical centres into other sites.^3,19 Public institutions are the most protective environment for the public for pharmaceutical and biotechnology trials, provided they have transparent and available guidelines on their interactions with the pharmaceutical industry.^20-23

References

1. Health and Medical Research Strategic Review. The virtuous cycle. Working together for health and medical research. Canberra: Canberra Info 1999.
2. Chalmers I. Underreporting research is scientific misconduct. JAMA 1990; 263: 1405-1408.
3. Bodenheimer T. Uneasy alliance — clinical investigators and the pharmaceutical industry. New Engl J Med 2000; 342: 1539-1544.
4. Angell M. The pharmaceutical industry — to whom is it accountable? New Engl J Med 2000; 342: 1902-1904.
5. Rennie D. Fair conduct and fair reporting of clinical trials. JAMA 1999; 282: 1766-1768.
6. Hailey D. Scientific harassment by pharmaceutical companies: time to stop. CMAJ 2000; 162: 212-213.
7. Weatherall D. Academia and industry: increasingly uneasy bedfellows. Lancet 2000; 355: 1574.
8. Larkin M. Whose article is it anyway? Lancet 1999; 354: 136.
9. Rogers v Whitaker (1992) 175 CLR 479.
10. Chalmers I. What do I want from health research and researchers when I am a patient? BMJ 1995; 310: 1315-1318.
11. Royal Australasian College of Physicians. Ethical guidelines in the relationship between physicians and the pharmaceutical industry. Sydney: The College, 2000.
12. National statement on ethical conduct in research involving humans. Canberra: National Health and Medical Research Council, 1999.
13. Pyle G. The drug-body snatchers; No cure, Mrs James, but thanks for all the money; Playing patients in the fast lane; It's the money they have to have. Sydney Morning Herald 13 Feb 2001: 1,4.
14. Pyle G. Patient drug tests enrich hospitals; Vulnerable used as guinea pigs but who guards the guardians? Sydney Morning Herald 14 Feb 2001: 1,4.
15. Savulescu J, Chalmers I, Blunt J. Are research ethics committees behaving unethically? Some suggestions for improving performance and accountability. BMJ 1996; 313: 1390-1393.
16. Wise P, Drury M. Pharmaceutical trials in general practice: the first 100 protocols. An audit by the clinical research ethics committees of the Royal College of General Practice. BMJ 1996; 313: 1245-1248.
17. Scroccaro G, Venturini F, Alberti C, et al. Registering clinical trials. BMJ 2000; 320: 1339.
18. Roughead E, Gilbert A, Primrose J, Sansom LN. Drug related hospital admissions: a review of Australian studies published 1988-1996. Med J Aust 1998; 168: 405-408.
19. Angell M. Is academic medicine for sale? New Engl J Med 2000; 342: 1515-1518.
20. Lemmens T, Singer PA. Bioethics for clinicians: 17. Conflict of interest in research, education and patient care. CMAJ 1998; 159: 960-965.
21. Emanuel EJ, Wendler D, Grady C. What makes clinical research ethical? JAMA 2000; 283: 2701-2711.
22. Boyd EA, Bero LA. Assessing faculty financial relationships with industry. A case study. JAMA 2000: 284: 2209-2214.
23. DeAngelis C. Conflict of interest and the public trust. JAMA 2000; 284: 2237-2238.

Authors' details

Reprints will not be available from the author.
Correspondence: Dr C A Commens, 20 Hillcrest Road, Pennant Hills, NSW 2120.
ccommensATmail.usyd.edu.au

©MJA 2001
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