Informed consent procedures and information about potential side effects of newly prescribed treatments present a classic dilemma. Although providing information about potential risks and side effects is necessary both from a medicolegal perspective and to maintain patient autonomy in a shared decision-making process, it can fuel patients' worries and negative expectations. There is ample evidence that the impact of these negative expectations, also known as nocebo effects, can significantly limit the efficacy and tolerability of drug treatments and the adherence to longer-term treatment regimens.2,4 Research efforts have been directed towards minimizing the negative impact of adverse effect information with proposed strategies including authorized concealment of side effects, framing the information provided, and educating patients about the potential influence of the nocebo effect. Although the outcomes have been mixed, the overall findings have been promising.

In a new study published in this issue, Clemens et al.3 explored an avenue that has long been advocated but received little attention in empirical research so far. In 2 preregistered large-scale online investigations (N = 999 participants), they aimed to explore an individual's perspective on side effect information as a first step to personalize this process. Specifically, they examined how the characteristics of expected side effects (eg, frequency, severity, and duration) and the individual's tendency to avoid information influence the desire for side effect information about a treatment for lower back pain. The findings revealed that participants' desire for more information about side effects depends on the frequency and severity (but not duration) of side effects. Notably, participants displayed a lower desire for information when the symptoms were less severe and less frequent. In addition, patients' tendency to avoid information led to less information seeking, whereas participants' level of contact with the healthcare system, presence of a chronic health condition, or history of chronic pain had no significant influence.

Given that it is the way, in which information is perceived rather than the information itself that influences the occurrence of nocebo effects, it is crucial to consider a patient's need or preference for information. It may be equally harmful to overload patients with information that trigger nocebo effects as it is to withhold information from those who require comprehensive disclosure. Therefore, adopting a personalized approach could be a significant step towards establishing an information process that genuinely facilitates optimal treatment outcome.

However, there are still unresolved questions that warrant further investigation. First, the findings by Clemens et al. suggest that patients engage in a deliberative process to assess which side effects are worth knowing about, even if there is a potential risk of inducing nocebo effects, and which information can be disregarded, either because the side effect is rare or would have limited impact. Such decision-making requires the ability to integrate diverse information, such as considering the low frequency of a side effect but acknowledging its severe consequences if it were to occur. Second, informing patients about potential side effects also serves an educational purpose. By alerting the patient to possible symptoms, healthcare providers increase the probability that patients respond appropriately, such as seeking medical assistance, particularly in cases where a causal link between treatment and side effect may not be obvious to the patient. Future studies should therefore take into account factors such as health literacy and explore strategies to providing information that preserves safety without triggering nocebo effects.

Third, although Clemens et al. conducted their study in an impressively large sample, it is important to note that participants were drawn from a community-based sample of adults in the United States and included individuals with and without a history of pain (although this factor had no moderating influence on the results). Further investigations are warranted to determine the generalizability of these findings to populations with diverse characteristics, such as individuals experiencing different types of chronic pain or elderly patients.

Fourth, in this well-controlled experimental study featuring a factorial design, participants were required to imagine possible medical situations rather than experiencing actual treatments. It is important to recognize that patients' inclination for information about a drug and their ultimate willingness to take it will be influenced by the characteristics of side effects (as demonstrated in this study) but also by the individual suffering and the desire for pain relief.

Most importantly, it is essential to acknowledge that a healthcare professional's decision to withhold information should not and cannot preempt a patient's decision not to receive that information. Withholding information where it is sought undermines the collaborative decision-making process between the patient and the healthcare provider, where offering side effect information plays a pivotal role in reaching a well-informed treatment decision. Thus, the choice to forgo comprehensive information should be made by the patient from an empowered position and a sense of agency, even if—or especially if—it involves authorized concealment. The study conducted by Clemens et al. underscores that we cannot make this decision on behalf of the patient. In both studies, participants expressed a strong desire for information about side effects—and, so far, our understanding of the factors that predict an individual patient's need for information in a given scenario is very limited.

This study provides the foundation for future research endeavors focused on customizing information regarding side effects to meet the needs of individual patients, all while mitigating the occurrence of nocebo effects. In forthcoming studies, these personalized approaches should integrate not only clinical considerations and patients' preferences for information but also take into account factors such as a patient's goals, available resources, individual challenges, and preferred communication methods (eg, graphical, written, oral, and peer-to-peer information) to convey both risks and benefits of a treatment. Whether this necessitates the enhancement of healthcare professionals' communication skills through comprehensive training, harnessing the power of AI systems that can provide empathic and high-quality responses,1 or a thoughtful combination of both remains to be determined.

Conflict of interest statement

The authors have no conflicts of interest to declare. U.B. receives funding from the Deutsche Forschungsgemeinschaft (German Research Foundation)—TRR 289 Treatment Expectation—Project Number 422744262. K.W. is supported by the National Institute for Health and Care Research (NIHR) Oxford Health Biomedical Research Centre, UK.

References [1]. Ayers JW, Poliak A, Dredze M, Leas EC, Zhu Z, Kelley JB, Faix DJ, Goodman AM, Longhurst CA, Hogarth M, Smith DM. Comparing physician and artificial intelligence chatbot responses to patient questions posted to a public social media forum. JAMA Intern Med 2023;183:589–96. [2]. Bingel U. Avoiding nocebo effects to optimize treatment outcome. JAMA 2014;312:693–4. [3]. Clemens KS, Vang M, Colloca L, Sieg M, Vase L, Ruble A, Geers AL. The desire for side effect information in pain treatment: an experimental analysis of contextual and individual difference factors. PAIN 2024;165:383-91. [4]. Colloca L, Barsky AJ. Placebo and nocebo effects. N Engl J Med 2020;382:554–61.