Informed consent and placebo

I read two books recently – 1) The Immortal Life of Henrietta Lacks by Rebecca Skloot and 2) Trick or Treatment? Alternative Medicine on Trial by Simon Singh and Edzard Ernst and there are just so many different thoughts on my mind right now about medical research. Over the past few months, I have learnt a lot about the technicalities of the drug discovery and development pipeline from bench to bedside. However, I have been and am still struggling to form an intelligent opinion on the ethics of medical research, in particular clinical trials. In the simplest terms, clinical trials for potential drug candidates are done in 3 phases, the aim of the first phase is to test the safety of the drug usually in healthy volunteers (with the exception of some drugs, e.g. anti-cancer drugs), the aim of the second phase is to evaluate the efficacy of the drug in a small patient population while the third phase is done to evaluate the efficacy of the drug in a larger patient cohort. Conceptually speaking, this framework is logical and rather robust in evaluating new drug candidates. A closer scrutiny reveals a paradox in the framework that makes me rather uncomfortable and I am really curious to find out how doctors deal with this paradox on a daily basis.

In order for clinical trials to make any sense, there must be a control group and the patients in this control group are given placebo instead of the actual drug. This is important because the placebo effect is a very real phenomenon. It has been observed that patients actually showed marked improvement just simply because they are being treated and they expect that the treatment will help them and not because of the effect of the drug. As Simon Singh and Edzard Ernst have alluded to on numerous occasions in their book, sometimes patients show improvements after obtaining treatment from alternative medicine practitioners simply because they believe that the treatment will help them. In order to distill the pharmacological effect of the drug from any potential placebo effect the patients might get from the action of taking the drug itself, a placebo-treated control group is necessary in clinical studies. For now, let’s bear in mind that the placebo effect involves patients’ expectations that the treatment is beneficial to them.

Another equally important aspect of clinical trials (at least in today’s world) is the need for informed consent. The Declaration of Helsinki was drawn up based on the fundamental principle of respect for the individual, their right to self-determination and the right to make informed decisions regarding participation in research, both initially and during the course of the research. In the book “The Immortal Life of Henrietta Lacks”, the darker side of early evidence-based medical research is presented. One of Rebecca Skloot’s interests was to find out whether or not Henrietta Lacks and her family members have given their informed consent regarding the use of the first immortalized human cell-line, HeLa, obtained from Henrietta Lacks for medical research. The problem with HeLa cells is that somehow scientists got to know from whom HeLa cells originated from and they began to look for Henrietta Lacks’ family members to satisfy their scientific curiosity about genetics, particularly genetics of cancer. Rebecca Skloot also brought up several notable cases in the US where there was no informed consent, for instance the 40-year long Tuskegee syphilis experiment to investigate the natural progression of syphilis in rural African-American men. There are numerous ethical problems with this study, which includes researchers lying to the participants in the clinical trials so as to observe the long-term progression of the disease. Penicillin was also not administered to the patients even though it is known to be an effective cure for syphilis in the 1940s (the study was conducted between 1932 and 1972). Today, at least in the developed countries, there is an emphasis on obtaining the informed consent of patients before enrolling them on clinical studies.

To me, the paradox, in short, is that it seems that the placebo effect might be reduced when informed consent from the patients is obtained. Patients will be told that there is a chance that they are given placebo instead of the actual drug and patients, especially those in the developed part of the world, might believe that they are not treated. In the end, is the overaching objective of finding a better cure for diseases more important than the objective of treating existing patients as human beings who deserve a right to perfect information?

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