What we don’t know about informed consent
Christine Pace and colleagues question whether developing countries are really lagging behind in the quality of their consent processes for participants in clinical trials. They argue that the available data fail to back up these claims, and say that we should suspend judgement until more rigorous studies are conducted.
The authors are members of the Department of Clinical Bioethics at the US National Institutes of Health. The opinions expressed here are the authors’ and do not reflect the policies and positions of the National Institutes of Health, the US Public Health Service or the US Department of Health and Human Services. Email: [email protected].
Many commentators in medical, bioethical and popular literature have voiced concern about the quality of informed consent given by research participants in developing countries. They claim that in some of these countries, low levels of education, poor access to health care, lack of familiarity with biomedical research and even gender roles may jeopardise the ability of prospective research participants to make fully informed and voluntary decisions.
Quantitative studies of the quality of informed consent are one way to assess the validity of these claims. These evaluate what the research participants understand about clinical trials they have decided to join, and how voluntary their decisions are. Such studies can also evaluate the characteristics of participants and their circumstances that are thought to have a critical influence on informed consent. Comparing data from similar studies in developed and developing countries could also illuminate any differences or similarities in the quality of informed consent in the two settings.
Given their aims, have any of these studies actually produced evidence for the widespread concern about the quality of informed consent in developing countries?
A dearth of data
Despite all the discussion and doubts surrounding informed consent, existing data are in fact scarce and limited, particularly from developing countries. To our knowledge, only six quantitative studies on the quality of informed consent of actual research participants (or in one case, the parents of child participants) in developing countries have been published; taken together, they surveyed only 423 individuals in four countries. [refs. 1-6] Although more studies have been conducted in developed countries, many of these have small sample sizes (with nearly half below 100) as well.
Taken as a whole the studies present a number of problems. The range in questions makes it difficult to draw comparisons across studies and settings, the questions are often imprecise or ambiguous, and at least three-quarters of the studies from developed countries assessed participants’ recall of the details of the trial, rather than comprehension at the time they decided to join.
The paucity and methodological problems of studies from both settings mean we lack evidence for any claims that informed consent is worse in developing than developed countries. Yet, while any conclusions are premature, the data may nonetheless yield some hypotheses about the quality of informed consent in developed and developing countries that could be further addressed in future studies.
There are indeed warning signs about participants’ comprehension and whether they are acting voluntarily, but in contrast to some claims, these warnings seem to apply to both developed and developing countries. In the available studies, comprehension was often incomplete; for example, only 10 per cent of mothers of children in an influenza vaccine trial in the Gambia knew that there was a placebo group, [ref. 4] and only 30 per cent of participants in phase I, II and III oncology trials in the US were aware that the treatment they were receiving was unproven. [ref. 7]
Several studies also reveal problems centring on participants’ knowledge that they were free to quit the trial. The most troubling data come from studies in Bangladesh and South Africa, [refs. 3, 5] though it is not clear how this compares with the industrialised world, since a question about quitting was asked in only one study from a developed country.
If at this point the data serve mainly as a reminder that problems with informed consent are not unique to developing countries, they also suggest that characteristics such as low levels of education or lack of access to health care should not be assumed to consistently predict a research participant’s comprehension or voluntariness. Indeed, several of the studies that have sought such correlations did not find them.
Just as important, we cannot assume that participants in clinical research in developing countries even have these characteristics. A study we recently conducted in Bangkok, Thailand, found that as many as 72 per cent of participants in an HIV trial had at least finished high school. [ref. 8] This is a reminder not only that developing countries themselves lie along a spectrum in terms of their educational and health care resources, but also that little is known about who participates in clinical trials in these countries, or, for that matter, in developed countries.
There is a clear need for more data on the quality of informed consent from a diversity of trial types and settings, and an equally important need to suspend our judgments until such data are available. Future studies must be rigorous, using validated instruments at the time of participants’ decision-making. With coordination and standardisation of these instruments, investigators could even use them to integrate formal assessment of the quality of informed consent into their protocols.
Seeking to better understand the strengths and weaknesses of the informed consent process should not be a distraction from the broader context of research ethics, however. Informed consent is an important ingredient for ethical clinical research, but it is only one ingredient, and does not obviate the need for careful consideration of the many other ethical challenges facing investigators and sponsors of clinical trials in developing countries.
The authors are grateful to Jim Lavery for his comments on the manuscript.
 Fitzgerald D, Marotte C, Verdier R, Johnson W, Pape J. Comprehension during informed consent in a less-developed country. The Lancet 2002; 360:1301-1302.
 Joubert G, Steinberg H, Ryst Evd, Chikobvu P. Consent for participation in the Bloemfontein Vitamin A trial: How informed and voluntary? American Journal of Public Health 2003; 93:582-584.
 Karim Q, Karim S, Coovadia H, Susser M. Informed consent for HIV testing in a South African hospital: Is it truly informed and truly voluntary? American Journal of Public Health 1998; 388:637-640.
 Leach A, Hilton S, Greenwood B, et al. An evaluation of the informed consent procedure used during a trial of a Haemophilus influenzae type B conjugate vaccine undertaken in The Gambia, West Africa. Social Science and Medicine 1999; 48:139-148.
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 Joffe S, Cook E, Cleary P, Clark J, Weeks J. Quality of informed consent in cancer clinical trials: A cross-sectional survey. The Lancet 2001; 358:1772-1777.
 Pace C, Grady C, Chuenyam T, et al. Unpublished data. 2003.