Unperceived similarities between clinical trials and quantum physics

1.

The randomized controlled trial (RCT) is the best design to determine cause‐effect relationships in biomedical research. This is applicable to any other branch of science. When one compares two interventions (for example, medicines) in a RCT, the results (or observations) can be attributable only to the medicines, provided biases have been appropriately controlled. At the design stage, clinical equipoise is the first condition any RCT must comply with to be ethically acceptable. Clinical equipoise means that investigators do not know which medicine has a better benefit/risk ratio; in other words, there is a genuine uncertainty1 of their comparative efficacy or effectiveness.2 This has been proven to be true, since only slightly over 50% of 860 phase 3 RCTs have shown that new treatments were better than the comparators.3 Thus, at study start, results of all RCTs are unpredictable, uncertain, and indeterminate.

Participants in a RCT can be subject to the Hawthorne effect. This refers to research participants' behavioural changes in response to their awareness of participating in a trial. The name comes from the manufacturing plant near Chicago in which several studies took place between 1924 and 1933, to assess the effects of lighting and breaks on the workers. It turned out that the workers' output increased during the studies, translating the effect that individuals changed their behaviour in response to being observed. In the Hawthorne effect, the observer (ie, the investigator) has no intention to affect the participant's behaviour. The Hawthorne effect has been linked to very different clinical research situations, both in healthy individuals and in patients,4, 5 including biochemical baseline changes in trial participants after their recruitment.6 However, a systematic review on research participants found that although most studies reported some effect, their heterogeneity prevented confidently inferring the size of the effect.7 The Hawthorne effect follows a time‐dependent curve, and the magnitude of the effect depends on the frequency and intensity of observations of participants.8

Quantum physics is one of the most difficult disciplines in science. There is a well‐known statement by Richard Feynman, a Nobel prize winner in Physics, that nobody understands quantum physics. Most of us have, at the very best, a poor understanding of what quantum physics is. We know that it elegantly and precisely describes the microworld, that of molecules, atoms, and particles: how these work and interact. But it is useless to describe what we can understand more easily, the macroworld, that of planets, and what happens in our everyday experiences—which is described by classical physics. Although quantum physics is counterintuitive, it has been successfully applied (thanks to mathematics) by many people resulting in the development of nuclear plants, computers, lasers, digital cameras, and magnetic resonance imaging. While classical physics can predict the results of a measurement or observation (certain, determinate), quantum physics can only calculate probabilities (uncertain, indeterminate). Thus, the essence of both RCTs and quantum physics is the uncertainty, the indetermination of the observations or results.

According to quantum physics, particles such as electrons or photons, can be described as both particles and waves: the “wave‐particle duality” concept. In the case of particles with mass, the wave is not a physical wave, but rather a mathematical description: the “wave function.” The wave function provides the probability of the distribution of the position of a particle, for instance, the electron. An electron behaves either as a wave or as a particle depending on the type of experiment used to try to characterize its properties, but it cannot be observed as both wave and particle. This is called the observer effect, meaning that the act of watching affects the observed reality, that is, the experimental findings. This happens regardless of who the observer is—an individual or a machine—and depends on the level of observation.9 So, the observer effect is a definite feature of quantum physics, and it should always be considered to be present to a greater or lesser extent in RCTs, usually named as the Hawthorne effect. Both share a common and important feature: the effects increase with more intensive observation. Despite huge and obvious differences, the wave/particle duality could be regarded to be similar to the individual/participant duality.

Two common features of quantum physics and RCTs are described here. Uncertainty is at the core of both. The observer effect is always present in quantum physics (and other branches of physics) and in clinical trials, although in the latter, it cannot always be observable, measurable.

COMPETING INTERESTS

There are no competing interests to declare.

Dal–Ré R. Unperceived similarities between clinical trials and quantum physics. Br J Clin Pharmacol. 2020;86:192–193. 10.1111/bcp.14126