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When the Last Hope Is a Coin Flip: Placebo Trials in Terminal Care

  • codeofcures
  • Aug 21
  • 5 min read

Updated: Aug 31

Are placebo-controlled trials ethical for terminally ill patients when the trials may represent their last hope?

By Crystal Kong and Chloe Cherng

Image from Grey’s Anatomy
Image from Grey’s Anatomy

You may have heard of Grey’s Anatomy–the long-standing medical show that has pulled millions of viewers over the last decade. Beyond the romance and drama, the show highlights the life of surgical interns and often raises real-life ethical dilemmas faced by doctors. One example is Derek Shepherd’s randomized placebo trial for patients with an incurable disease called Alzheimer’s. The trial involved a minimally invasive procedure where patients received a drug or a placebo via injections into the brain. In this storyline, patients who had run out of options turned to Derek’s trial as their last hope. However, some patients were not given the treatment: instead, they were given a placebo, leaving them with little to no chance of improvement This raises an uncomfortable question: how can placebo-controlled trials that withhold treatment from desperate terminally ill patients be ethically justified? 


What is a Placebo?

A placebo is often used as a control in experiments alongside the treatment. 

In terms of clinical trials, it appears and behaves like the real medication, but it contains no active ingredients and has no actual effect on the participants. When testing a new medication, some receive the treatment while others receive a placebo. The usage of a placebo is crucial due to the placebo effect. 


The placebo effect occurs when patients experience real improvement in their symptoms after taking a placebo. There are numerous theories for the existence of this effect: the patient is on the verge of recovery, the act of receiving care triggers a biological response, or the patient believes effectiveness is inevitable. Therefore, a placebo is necessary in clinical trials to determine if improvement is due to the treatment or placebo effect. These trials are known as placebo-controlled trials (PCTs). However, the phenomenon is not effective when pertaining to serious conditions, as it primarily affects symptoms that are regulated by the brain. Thus, there are many ethical guidelines for the usage of placebo controls in research. 


There are four cases where PCTs are generally ethically acceptable according to a review of ethically acceptable uses of placebo (Millum 2014). First, when no proven effective intervention exists for the condition under study, or when the placebo is compared against an investigational treatment added to standard care, the use of a placebo is generally uncontroversial. This also applies when treatments work in certain populations, but their effectiveness cannot be assumed in others. Placebos become helpful and not ethically controversial as they help establish whether a treatment is effective. Second, PCTs are permissible when withholding treatment would expose participants only to temporary discomfort or minor delays in symptom relief, with no risk of serious or irreversible harm. Third, when a condition responds inconsistently to both established therapies and placebos—such as depression—placebos provide a reliable baseline to evaluate whether new interventions outperform natural variability or psychological effects. Finally, PCTs are ethical when participants are not deprived of interventions they would otherwise receive, and when the research is designed to benefit the host population. Across these cases, the key principle is that when a placebo is used, it must not cause undue harm, irreversible damage, or exploitation of vulnerable patients. 


Ethics in PCTs for Terminal Illness

For patients with terminal illnesses with no available cure, such as advanced cancer or Alzheimer’s, researchers find that their participation in PCTs can advance scientific understanding and develop potential treatments. In some cases, the patient is undergoing palliative care, whether it be during the end-of-life stage or progressing towards it. When this occurs, the involvement of patients in research becomes an ethical issue because patients must accept the risk of receiving a placebo, potentially diminishing all hopes for recovery if the treatment is deemed effective. 


Though these cons may scare patients, a patient’s participation in these trials is based on having complete autonomy. Before entering a trial, patients and their families are well informed about the risks. Those who consent rely on their luck and hope to be selected to receive the drug. In addition, terminally ill patients can have a shift in perspective, making them more likely to accept the trial. Some see PCTs as their last hope and would prefer to be at risk of getting the placebo instead of the treatment than giving up all hope by not being in the trial at all.


PCTs also create ethical tensions for doctors. As doctors, it is their duty to act in the best interest of their patients by providing them the highest standard of care they can. Thus, giving a patient a placebo may feel like an “abandonment” of that responsibility, especially when the patient is desperately seeking treatment. Doctors are forced into a difficult ethical debate: choosing between their duty to provide immediate care to the patient in front of them and their responsibility to advance knowledge that may benefit countless patients in the future. Informed consent can help address this ethical tension, but even when patients agree to these risks, many physicians feel conflicted as they struggle to balance compassion and science. 


In PCTs involving patients with terminal or life-limiting illnesses, crossover designs are strongly encouraged instead of a pure placebo. This provides patients at least some access to the potential benefits of the treatment. Doctors must ensure the risks of dying before crossover are minimized in order to have the PCTs in the first place. However, if the disease is rapidly fatal and progressive, crossover might not happen for the placebo patients to benefit. In these cases, doctors ensured to the best of their ability that the individuals were fully aware of all possible outcomes of the trials, and that ethical measures were taken in the best interest of the participants.


Conclusion

When it comes to clinical research with the participation of volunteers, ethical issues are bound to arise. Especially when the trials involve terminal illnesses, it becomes difficult for doctors to balance patient care with scientific progress. Research suggests that many families understood and even embraced this tension. One study found that while 14% of the relatives considered the participation of their loved ones in research a bit burdensome, 10% considered it a bit stressful, and 83% considered it to be valuable. The survey conducted showed that decisions were often made jointly between patients and their loved ones and, overall, most relatives expressed pride and respect for the patient’s participation. This reflects the perspective of terminally ill patients who are seeking a personal cure but also desire to be an essential part of advancing medicine. For this reason, ethical guidelines exist for PCTs and must be followed to take place. Ultimately, while conflicts will always remain, doctors strive to uphold these standards to ensure research is conducted as ethically as possible. PCTs play a significant role in medical progress, helping to develop treatments that can offer hope to patients facing serious illnesses and improve their quality of life.



Works Cited

Council for International Organizations of Medical Sciences. (2002, October).

International ethical guidelines for biomedical research involving human subjects. PubMed. https://pubmed.ncbi.nlm.nih.gov/14983848/ 

Daugherty CK;Ratain MJ;Emanuel EJ;Farrell AT;Schilsky RL; (n.d.). Ethical, scientific,

and regulatory perspectives regarding the use of placebos in cancer clinical trials. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. https://pubmed.ncbi.nlm.nih.gov/18227527/ 

Ethical use of placebo controls in research. AMA. (n.d.). https://code-medical-

Millum, J., & Grady, C. (2013, November). The ethics of placebo-controlled trials:

Van Esch, H. J., Stoppelenburg, A., van Zuylen, L., van der Rijt, C. C., & van der Heide, A.

(2022, December). When a dying patient is asked to participate in a double-blind, placebo-controlled clinical trial on symptom control: The decision-making process and experiences of relatives. Palliative medicine. https://pmc.ncbi.nlm.nih.gov/articles/PMC9749009/ 



 
 
 

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