Clinical trials are a big part of medical research and have lead to some amazing breakthroughs in the way we treat everything from diabetes to cancer. One common type of trial is known as a “double-blind” clinical trial. During this type of trial, half of the participants receive a placebo instead of the medication being tested. No one, even the doctors administering the drug, knows who is receiving the placebo and who is receiving the actual medication.
While it can be an effective method for removing the variable of researcher bias, it does raise an interesting ethical question. Are there ethical concerns with providing a placebo for a cancer patient, for example, who might be participating in a study as a last-ditch effort to survive?
Why use placebos in clinical trials?
Placebos have been used in clinical trials for nearly as long as there have been clinical trials. The introduction of a placebo, or sugar pill, as they’re colloquially known, is used to measure any placebo effect variable within the results of the trial.
The placebo effect is observed when a patient has a positive result from taking a placebo. In essence, the patient’s belief in the treatment creates a result. This result might be due to the patient’s perception, but there is nonetheless a measurable change in the patient’s health’s or well-being.
As a side result, the use of a placebo can also be used to eliminate or reduce research bias. Researchers might be more willing to select trial participants with a terminal diagnosis, for example, if a double-blind scenario isn’t being used. These terminal patients might be looking to find a miracle in a new experimental drug. These selections could encourage bias in the results of the trial.
Ethical concerns for placebo use
There are multiple schools of thought when it comes to the ethics of placebo use in clinical trials. Placebos make sense for drugs and treatments in their first clinical phase. During Phase I, the optimum dosage is determined and any major side effects present themselves. This stage of the trial is almost always conducted with healthy adult volunteers, and the placebo provided to half of these volunteers provides a source of valid scientific information.
In later phases of the trial, the question of ethics becomes an issue. Many researchers feel it is unethical to withhold a treatment that has had its efficacy proven during earlier trial phases just to collect additional scientific evidence. Withholding such treatment is the antithesis of the physician’s oath to do no harm.
This argument puts commercial pharmaceutical companies at a disadvantage, mainly because they are under significant pressure to prove their new treatment is somehow better than any existing treatments. Existing treatments, on the other hand, have only had to prove themselves more effective than a placebo.
Some professionals feel it is unethical to conduct trials without the use of placebos, arguing drug trials are not a black-and-white industry. There are many shades of gray that have to be considered—up to and including the fact that a double-blind trial isn’t always able to establish drug efficacy.
Greater risks than ethics
Additionally, though this has little impact on ethics, studies completed without a placebo group might not have all the information they need to safely prescribe and market a drug. A trial conducted to study the risk of myocardial infarction associated with the use of a drug known as rofecoxib utilized two groups:
- One group taking just the drug
- One taking the drug along with a non-steroidal anti-inflammatory drug like naproxen
With no placebo group, it was impossible to tell if the use of rofecoxib increased the risk of myocardial infarction or if naproxen decreased it. As a result, the drug was eventually pulled from the market because of a high risk of sudden cardiac death after another 3-year study was conducted.
What about ‘Right to Try’ laws?
Right to Try laws have been passed in 33 states, as of the time of this writing. These laws allow terminally ill patients to bypass the FDA’s “Compassionate Use” application process and receive treatment utilizing experimental drugs that have passed Phase I of their clinical trials. Compassionate use applications can take months or years to be approved, and many terminally ill patients just don’t have that kind of time to wait.
Unfortunately, these Right to Try laws could have a negative effect on clinical trials. Patients may be more likely to utilize the Right to Try option rather than signing up for a clinical trial. Under the law, patients will be guaranteed treatment with the experimental drug, while patients who sign up for a trial might only have a 50% chance to actually be treated with the drug.
The Right to Try laws are often the last chance a terminally ill patient has, and should be continued for compassion’s sake if no other reason. That said, their effects on participation in clinical trials should be taken into account.
Finding the balance between ethics and science
There are a growing number of medical professionals who consider the use of placebos unethical, especially when the efficacy of the treatment has already been proven. The most likely course of action will be to find a balance between the ethics and the science of the situation, and anyone who’s ever worked on an ethically gray topic knows how difficult that can be.
It’s hard to say whether we should compromise the use of placebos because of these ethical considerations when the same placebos may end up providing information that could protect or save lives once the drug completes its clinical trials.