Although the idea of equipoise is a philosophical concept, it’s important for reporters to understand because it underlies the bioethical justification for any and all clinical trials. Equipoise is, originally, “a state of genuine uncertainty on the part of the clinical investigator regarding the comparative therapeutic merits of each arm in a trial,” according to Benjamin Freedman, PhD, who discussed it in his 1987 paper in the New England Journal of Medicine. Or more plainly, researchers “have to admit they don’t have the right answer.” But Freedman proposed a slightly revised clinical definition of equipoise: “genuine uncertainty within the expert medical community — not necessarily on the part of the individual investigator — about the preferred treatment.”
Deeper dive
If a single researcher knows that a specific therapy is better than all others, he or she is ethically obligated to offer that treatment. But this definition is flawed, allowing the individual biases of a particular research to potentially rule out the majority of clinical trials. Therefore Freedman amended the idea to refer to a medical consensus, setting up what is “now considered to be the fundamental or guiding principle concerning the ethics of enrolling patients in randomized clinical trials.”
Clinical equipoise is essential when a major goal of clinical research is to find better treatments than already exist for conditions that need it, such as pancreatic cancer or neurodegenerative diseases. This concept enables large numbers of patients to safely enter most clinical trials because they know they will receive, at the very least, the current recommended first-line therapy.
Equipoise is one of the considerations Institutional Review Boards must weigh in determining whether a proposed trial design is ethical. It is also the reason certain types of studies, such as one randomizing children to be fully vaccinated or unvaccinated with vaccines that have already been approved through the usual processes, as many anti-vaccine advocates request, will never be approved by an IRB. It would be unethical to deny effective prevention of infectious diseases to children, so outside of clinical trials for a brand new vaccine, only studies of a vaccine whose long-term benefits are genuinely uncertain will be approved. Even in those trials, the control arm is often a different (already commonly used and recommended) vaccine or, if it is an inert substance, the children will typically receive the vaccine 6 or 12 months later.
Still equipoise is rarely straightforward, and medical ethicists continue to debate about it in medical journals. The simple fact that clinical benefit can be measured in different ways, including quality of life, makes it challenging to consider, but that’s why researchers get approval from Institutional Review Boards before moving forward with a trial. Meanwhile, any journalist exploring the side effects and risk-benefit balance of a treatment will want to give thought to the equipoise underlying clinical trials for the therapy they are writing about.