From the initial pool of 279 non-duplicate records, 17 articles met the inclusion criteria (see Fig. 1). As shown in Table 4, most of these articles were published between 2019 and 2023 (11 out of 17). The studies vary in design, with most being qualitative studies or conceptual analyses, and one randomized controlled trial (Publication 12). Sample sizes and populations differ widely; most papers (10 out of 17) were conceptual pieces while the empirical ones focus on healthcare professionals (e.g., surgeons, physicians) or patients with specific conditions such as chronic pain.
Ethical issues
In total, we inductively derived 37 discrete ethical issues (“codes”) from the 17 articles. Each distinct concern was assigned a single code. Through iterative qualitative analysis, these codes were grouped into five overarching themes:
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1.
Sociocultural and contextual factors.
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2.
Implementation and logistics.
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3.
Informed consent.
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4.
Patient health behavior and dynamics.
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5.
Therapeutic relationship.
Each theme captures related ethical discussions that cut across multiple articles. In the following section, we inspect the five themes with their 37 corresponding codes. In Table 4 we list the theme, code, corresponding publication (numbered as per Table 3), a brief explanation of the code and an example quote68,69,70,71. This allows readers to see both a concrete instance (via the quote) and the scope (which publications) for each code (a discussion on using quotes in qualitative studies can be found here72). After Table 4 we provide a summary text for each theme, where codes are printed bold, and publication numbers are mentioned again.
Sociocultural and contextual factors
The theme of Sociocultural and Contextual Factors became apparent in the discourse on placebo use. This theme encompasses the intricate and often contentious perspectives that various stakeholders hold regarding the legitimacy and utility of placebos within healthcare settings.
Publications coded under Alternative Medicine (Publications: 17, 5, 6, 9, 10, 13) reveal a recurrent concern regarding the potential for placebo use to foster or reinforce beliefs in the efficacy of the placebo itself or the broader concept of mind-body healing. A salient quote from publication 17 encapsulates the apprehension that such beliefs could be mistakenly held as sufficient for curing serious illnesses, thus neglecting established treatments. This suggests a risk of placebos contributing to an overvaluation of “positive thinking” in healing, possibly leading to the avoidance of medically proven interventions. Publications 3, 7, 13 and 14 also suggest a possible paradigm shift that pertains to the cultural and ethical discourse around placebo treatments potentially advancing and redefining their role within medical practice. A forecasted change, as detailed in publication 13, might see placebo therapy integrated into a legitimate clinical method, albeit in specific situations delineated by clear guidelines. The theme further engages with the influence of social norms (Publications: 3, 13) on patient-physician interactions, particularly how patients’ expectations of treatments are constructed and sometimes confronted in the context of OLPs. Publication 3 provides an account of a participant suggesting that OLPs could challenge social conventions, indicating a potential shift in the dynamics of patient-clinician relationships. Lastly, publications 8, 13 and 17 contribute to a discussion on how the use of placebos might affect patient and parental attitudes view on medicine. A noteworthy concern is that an increased reliance on placebos could inadvertently escalate the expectation for immediate “treatments” for every symptom, potentially exacerbating issues within medical practice as highlighted by publication 17. In summary, this theme underscores a complex interplay between sociocultural and contextual factors and the use of placebos to justify the use of alternative medicine. The data indicates both concern for the potential misappropriation of placebos and an optimistic outlook for their ethical integration into medical practice, subject to ongoing cultural and ethical discourse.
Implementation and logistics
The exploration of OLPs within the systematic review highlighted a nuanced spectrum of implementation and logistical considerations critical to their integration into medical practice. Acceptability was a pivotal concern, with intervention preference varying widely; some patients exhibited a readiness to embrace OLPs as an extension of their current treatment regimen (Publications: 2, 3, 4, 5, 6, 7, 8, 9). However, the potential for OLPs to serve as a dose extending OLP alongside active medication was met with both intrigue and scepticism, prompting calls for more definitive evidence to validate this application (Publications: 2, 3, 4, 8, 9, 11, 13, 15, 17). The issue of blinding in placebo-controlled trials was also broached, with publications indicating a challenge in maintaining the rigour of double-blind placebo research design when comparing open with hidden placebos and evaluating them against the best available treatment (Publications: 8, 9, 14). Doubts concerning the clear efficacy of OLPs were prevalent, with several studies suggesting a strong imperative for future research to provide solid evidence for their effectiveness, as OLP efficacy not clear yet (Publications: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 14, 16, 17). Indeed, future work is needed by large-scale, pragmatic randomized trials to assess the true potential of OLPs, which was a recurrent theme, emphasizing the importance of robust, evidence-based conclusions (Publications: 1, 4, 5, 6, 7, 8, 9, 11, 12, 16). Legal aspects emerged as a barrier to the prescription of OLPs, with practitioners expressing concern over the consequences of possible negative outcomes from OLP use (Publications: 3, 4). Opinions were divided; some viewed OLPs as comparable to other prescriptions, while others called for additional provider training or patient education to ensure appropriate use, which is summarized under the code ‘logistics’ (Publications: 3, 7, 8, 9, 17).
‘OLP by Proxy’ was acknowledged as a phenomenon, particularly in paediatric care, where the belief systems of parents could significantly influence the placebo response in children, highlighting a complex dynamic in placebo use (Publications: 10, 11). The cost of OLPs was another factor affecting their acceptability, with patients hesitant to incur costs for an inert substance, suggesting economic factors need to be considered in the implementation strategy (Publications: 2, 7, 14).
Lastly, the notion of replacing drugs by OLPs was contemplated, especially in the context of treatments for conditions such as ADHD, where the goal might be the gradual withdrawal from active drugs. This theme suggested a careful and considered approach to introducing OLPs into the treatment regimen (Publications: 2, 9, 11).
Throughout this theme, it was apparent that while there is an underlying positive sentiment towards OLPs, their acceptance and practical application hinge on a multitude of factors that span the spectrum of ethical, legal, logistical, and economic considerations. The synthesis of these insights portrays a healthcare landscape cautiously navigating the potentialities of OLPs, with a clear consensus on the need for continued investigation and dialogue.
Informed consent
In the context of informed consent within the use of OLPs, this theme has uncovered several dimensions of concern and consideration. The ambiguity inherent in the disclosure process was highlighted, with some practitioners opting for vague language to introduce placebos to patients. This strategy involves offering OLPs with phrases like “here’s something you could try and let’s see if it works,” which, while avoiding definitive claims about the treatment keeping up ambiguity, could lead patients to assume they are receiving an active medical intervention (Publications: 1, 6, 7). The necessity for clinician OLP literacy is underscored, pointing to a need for comprehensive training to ensure that the wider adoption of OLPs is accompanied by accurate patient understanding and expectation management (Publications: 5, 7, 8, 9, 11). Publications suggest that OLPs are consistent with IC values and it is both achievable and necessary to mitigate the ethical risks associated with OLP use (Publications: 5, 7, 13, 16, 17).
The definition of OLPs was also a focal point of debate. It was proposed that recent discussions around OLPs, which often include considerations of communication, empathy, and other contextual factors, should not blur the conceptual boundaries of OLP and other non-specific effects (Publications: 3, 9, 15). OLP Disclosure practices are central to the ethical deployment. Evaluating whether the disclosures made in open-label placebo studies would be ethically acceptable in clinical encounters first requires a clear understanding of what is divulged to participants. Publications stressed that the disclosures and informed consent in clinical trials must be subject to careful moral scrutiny to differentiate them from disclosures in other therapeutic contexts (Publications: 1, 2, 5, 7, 9, 11, 15). Furthermore, the influence on decision-making was considered important. It was posited that the way in which OLPs are presented could independently influence how patients understand their illness and symptoms, and thus their maintenance and healthcare-seeking behaviour (Publications: 1, 11). A critical concern raised was the potential for patients not to fully understanding the consent and hence the concept of OLPs, raising alarms about the consistency of messaging and comprehension across care teams and between clinicians and patients (Publications: 7, 8, 11). Moreover, the notion of patients’ right to ‘not know’ or to know less was discussed, emphasizing the ethical complexity in ensuring that patients can consent to OLP use without forfeiting their right to fully informed consent or the benefits of a safe and transparent patient-clinician relationship (Publication: 13). In synthesizing these insights, it becomes evident that informed consent for OLPs is a multifaceted issue that intersects with ethical, communicative, and educational domains, each demanding careful attention to uphold the integrity of patient care and the ethical standards of clinical practice.
Patient health behaviour and dynamics
In the sphere of patient health behaviour and dynamics, this theme presents a multifaceted view informed by patient expectations and the perceived harms versus benefits of OLPs. Expectations play a crucial role in the acceptability of placebo treatments, with outcomes depending greatly on how patients anticipate the effectiveness of treatment (Publications: 5, 9, 11). Physicians need to carefully evaluate harm vs. benefits (Publications: 3, 7, 9, 13, 15). The potential influence of OLPs on healthcare-seeking behaviour is complex. On the one hand, they can empower patients, providing a sense of control and comfort. Yet, there are once more concerns that by being prescribed placebos, some patients may lose faith in mainstream medicine, erroneously believing that placebos legitimize complementary and alternative treatments, which influences help-seeking behaviour (Publications: 5, 6, 16).
The phenomenon of nocebo effects—where an inactive substance causes negative outcomes—is also a significant concern. This includes the potential for unknown risks or ‘nocebo effects,’ where the expectation of an adverse effect by patients precipitates or exacerbates the experience of that symptom (Publications: 2, 3, 8, 9, 17). Moreover, there is the issue of overestimating the positive effects of OLPs. While considerable research remains to be done, there is a need for honesty about the current understanding of the boundaries of placebo potential and the realistic communication of what placebo responses can and cannot do for people (Publications: 2, 5, 7, 10, 11). Overprescription of drugs is a concern tied closely to the use of OLPs. The widespread use of placebos could intensify the already prevalent expectation for treatments for every symptom, potentially leading to an overreliance on medication in general, which may crowd out other forms of care or lead to the devaluation of non-pharmacological treatments and to overprescription of drugs (Publication: 17). Lastly, the issue of structural injustice was addressed. Assumptions made about patients when they are giving testimony can be rooted in biases and power imbalances between social groups. When OLPs are integrated within minority or participant groups that have been historically disbelieved or devalued, there is a risk that this might reinforce social disparities. This runs the risk of exacerbating these imbalances (Publication: 16).
Therapeutic relationship
The dynamics within the therapeutic relationship are critically reflected upon within this theme. In environments where medical expertise is rapidly expanding and the lexicon becoming ever more specialized, the relationship between healthcare providers and patients is strained, with the latter often feeling overwhelmed and isolated (Publications: 2, 3, 10, 14, 15). Agency, particularly in the context of OLPs, is emphasized as a key component of the therapeutic relationship. It is recognized that the role of agency in placebo effects is complex and traverses the clinical context, necessitating a broader view of potential for promoting placebo effects in various domains. This involves understanding the underlying mechanisms of how they can promote agency and benefit patient outcomes (Publications: 3, 9, 10, 11). Additionally, the concept of autonomy within the therapeutic relationship is underscored, highlighting the importance of patient autonomy in any placebo-centric practice. The review suggests that autonomy plays a critical role in domains far beyond the immediate clinical encounter (Publications: 7, 9, 10, 14, 17).
Deception is a contentious issue that can include offering false hope, the downplaying of risks and ambiguously formulated messages that may foster more positive expectations than the evidence justifies. The fine line between justified optimism and exaggerated confidence presents a moral dilemma, where placebo-based approaches must operate within the bounds of truthfulness (Publications: 1, 5, 8, 15).
The impact of OLPs on long-term health outcomes and the potential for blame was discussed, acknowledging the uncertainty about how different patient groups may internalize the use of OLPs. There is a risk that patients, especially those with medically unexplained symptoms, may internalize blame, which could be mitigated by how practitioners frame the use of OLPs (Publications: 6, 9, 10, 11, 14, 17). Paternalism in the therapeutic relationship was also critiqued, particularly when researchers assume a psychogenic mechanism for patients’ experiences, leading to the use of placebos rather than a conventional pill, potentially even without the patients’ full understanding or consent (Publications: 15, 16). Responsibility in prescribing OLPs is highlighted, posing the question of the ethical considerations that fall within the bounds of medicine and what is considered difficult care. The necessity for clear communication about the influences on placebo responses is emphasized, especially regarding informed consent processes (Publication: 10). Lastly, trust is identified as a cornerstone of the therapeutic relationship, with concerns that the prescription of placebo treatments could undermine trust in physicians, particularly if there is a perceived imbalance in the relationship (Publications: 5, 9, 12, 13, 14, 17).
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