Informed consent in clinical trials: ethical challenges

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You might have heard this a thousand times, but here is a restatement because it’s true: patient recruitment is the most painful process in the clinical trial. Of course, the term entails some sub-processes, among which informed consent probably ranks first in the level of time consumption and ethical challenges. Here we discuss five controversial issues that are causing trial conductors frequent headaches.

Linguistic, religious and cultural barriers

An informed consent form is required to provide patients with adequate information about the research including, but not limited to the purpose, the procedure, and potential risks. Simplifying these details to the extent that patients can fully understand is already a challenge, let alone translating into other languages.

With the globalization trends of clinical trials, it is vital that trial managers make clear of the necessary information to patients who don’t speak English. Yet misunderstandings do occur in the translation process that may lead to patients having inadequate information before signing the form or wrongly perceiving some details.

Other barriers facing trials with global sites are religious and cultural barriers. In some religions, it is against the rules of behavior to undergo some procedures in the trials, for example, taking blood samples is prohibited by the Jehovah’s Witness. In terms of culture, though in Western countries adult patients are expected to make decisions on their own, in Indian villages anyone must consult with all community members before deciding on anything. Trial conductors need to find a way to bridge the gap between scientific fulfillments and religious and cultural influences.

Patients’ perception

In most cases, patients are not willing to take part in clinical trials because they believe that trials do more harm than good. The idea of being a ‘lab mouse’ is not a bit appealing to patients who are in need of a concrete answer to their sickness. Most of the time it takes a long time for them to ponder over the decision to participate and they may even say no.

The ethical challenge presented here is to what extent potential risks and side-effects should be disclosed to these patients. If too many side-effects exist, they may feel discouraged to take part in the trial, which in turn might mean denying beneficial treatments to themselves. On the other hand, not providing patients with enough information is against the guidelines in Good Clinical Practices (GCP).

Special cases include children and vulnerable groups – essentially people who are unable to protect their own interests. Children above 7 years old are required to give a ‘child consent’ in addition to their legal guardians’ ones. Persuading these groups to join trials is challenging, especially when the prospective subjects themselves refuse while their legal representatives nod their heads.

False expectation and therapeutic misconception

The term ‘therapeutic misconception’ shouldn’t be foreign to clinical trial investigators and managers. The misconception occurs when a subject confuses the purpose of the trial, which is to test the efficacy of a new drug or treatment, with the purpose of ordinary treatment, which is to cure the patient’s illness. Basically, the patient thinks that participating in the trial is supposed to treat his disease while in fact, researchers are only trying to test whether or not the drug can do such thing. Although in some cases research subjects do receive the best treatment through clinical trials, this is not what trials aim at. The fact that patients enrolled in trials are not the direct beneficiaries can be challenging to explain, and to convince them to join the research.

Yet this is just one type of false expectations. Whereas in the case of therapeutic misconception, patients tend to exaggerate the benefits they might receive, the other end witnesses their disapproval of trials due to historical frauds and misconducts. These patients hesitate to join trials for fear of harmful impacts on their health, mostly due to fraudulent scandals of clinical trials in the past.

Deception and the use of placebo

In a double-blind randomized controlled trial, researchers test the efficacy of the drug against non-treatment. Therefore, a placebo (which looks exactly like the tested drug but has no therapeutic effect) and the drug are randomly distributed among patients with neither subjects nor investigators having awareness. The point is to deceive subjects into believing that they are receiving the effective treatment. In signing the informed consent form, they have agreed that they will not know whether they are given the drug or the placebo.

This would not be a problem if there wasn’t any case where a lack of treatment-exposed patients to harm, or even death. Using a placebo is definitely unethical in these situations because the benefits of enrolled subjects are sacrificed for the sake of scientific achievements. Researchers can choose to do a cross-over study where at one point the two groups of patients are switched so that both equally receive treatments. An active-controlled trial is also an alternative option here, though there is controversy over the effectiveness of this kind of trial design in determining the differences between the tested drug and non-treatment.

Conflict of best treatment

The ethical norm is that patients should always receive the best treatment available. If the tested treatment turns out to be highly effective, then nothing else needs to be said. However, the problem crops up when the drug used in the trial ends up being worse than the standard ones. By taking part in the trial, patients are denied the best treatment.

This seemingly too high an opportunity cost to pay greatly deters patients from signing the informed consent form and joining the trial. There has been a solution where there exists ‘honest professional disagreement’ among doctors as to what treatment is best. Nonetheless, a debate is still stirred up in extreme cases such as a surgical procedure versus orally taking medicines.

In short, it is undeniable that informed consent is a complicated process that has to deal with serious ethical challenges. That’s why an Institutional Review Board (IRB) or Institutional Ethics Committee (IEC) must present in any clinical trial in order to tackle these aforementioned problems if they happen to come up. Though the biggest purpose of the trial is to determine the efficacy of the tested drug, trial conductors should always pay much attention to the benefits of research subjects.

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