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Placebos in the context of clinical practice Lauri Teivonen lääketieteen kandidaatti Helsinki 01.03.2021 Tutkielma lauri.teivonen@helsinki.fi Ohjaaja: Pekka Louhiala HELSINGIN YLIOPISTO Lääketieteellinen tiedekunta
i.
HELSINGIN YLIOPISTO − HELSINGFORS UNIVERSITET
Tiedekunta/Osasto − Fakultet/Sektion – Faculty Laitos − Institution – Department
Lääketieteellinen tiedekunta Medicum
Tekijä − Författare – Author
Lauri Teivonen
Työn nimi − Arbetets titel – Title
Plasebot käytännön lääkärintyön kontekstissa
Oppiaine − Läroämne – Subject
Lääketiede
Työn laji − Arbetets art – Level Aika − Datum – Month and year Sivumäärä -
Syventävä tutkielma Maaliskuu 2021 Sidoantal - Number
of pages
21
Tiivistelmä − Referat – Abstract
Plasebon käsite on usein helpoin ymmärtää lääketutkimuksen yhteydessä. Tällöin plasebon
odotetaan olevan tehoton vertailuaine, jotta tutkittavan hoitomuodon vaikutukset pystytään
erottamaan ja osoittamaan. Tästä huolimatta suuri osa lääkäreistä ympäri maailmaa kertoo
kyselytutkimuksissa käyttävänsä jotain plaseboksi katsomaansa valmistetta tai menettelytapaa
kliinisessä työssään. Tämä hankalasti määriteltävä termi sisältää tosiasiassa laajan ja
monivivahteisen joukon tapoja hoitaa potilasta. Klassisen, tehottomaksi mielletyn sokeripillerin tai
suolaveden ohessa plaseboiksi mielletään vaihtelevasti vitamiineja, antibiootteja, heikkoja
kipulääkkeitä, perusvoiteita ja jopa aiheettomia verikokeita. Kliinikon oma määritelmä plasebolle
vaihtelee sekä kulttuurien ja kieliryhmien välillä että tämän erikoisalasta ja kokemuksesta riippuen.
Tämän tutkielman tavoitteena on kriittisesti tarkastella plasebon kliinistä käyttöä koskevaa
tutkimustietoa viimeisten vuosien ajalta. Kuudessa tuoreessa kyselytutkimuksessa paljastuu, että
plasebon tietoinen käyttö on usein paitsi pyrkimys saada aikaan potilaan hoitoa tehostava
plasebovaikutus, myös kliinikon tarvitsema työkalu erilaisten potilas-lääkärisuhteen haasteiden
kanssa toimimiseen. Taipumus hyödyntää perusteettomalta tuntuvaa hoitoa saattaa juontua
kliinisen päätöksenteon luonnollisesta hankaluudesta. Tuloksia tarkastellaan eettisestä
näkökulmasta; nykyisessä potilaan itsemääräämisoikeutta kunnioittavassa hoidossa plaseboihin
liitetty harhaanjohtaminen nähdään perustavanlaatuisena ongelmana. Tässä tunnistetaan tarve
panostaa ilmiön tarkasteluun laajemmin jo lääketieteellisen peruskoulutuksen yhteydessä.
Avainsanat – Nyckelord – Keywords
Placebos ; Ethics, Clinical ; Physicians, Primary Care
Säilytyspaikka – Förvaringställe – Where deposited
E-Thesis
Muita tietoja – Övriga uppgifter – Additional informationii.
HELSINGIN YLIOPISTO − HELSINGFORS UNIVERSITET
Tiedekunta/Osasto − Fakultet/Sektion – Faculty Laitos − Institution – Department
Faculty of Medicine Medicum
Tekijä − Författare – Author
Lauri Teivonen
Työn nimi − Arbetets titel – Title
Placebos in the context of clinical practice
Oppiaine − Läroämne – Subject
Medicine
Työn laji − Arbetets art – Level Aika − Datum – Month and year Sivumäärä -
Thesis March 2021 Sidoantal - Number
of pages
21
Tiivistelmä − Referat – Abstract
Placebos tend to get regarded as inactive, ineffective treatments with the deceptive
appearance of genuine medicine. However, a majority of physicians around the world
report applying some form of treatment that they perceive as placebos in their clinical
practice. What they mean by placebos often includes a vast and heterogeneous group of
interventions far removed from the inert substance as placebos are understood in the
context of a clinical drug trial. A vague intention to evoke a beneficial placebo effect is but
one of many reasons given for this practice, and from six recent empirical studies it
emerges that clinicians tend to employ what they perceive as placebos to cope with
uncertainty in difficult situations where patient expectations or needs are not being met.
The ethics and ramifications of placebo and clinical management through perceived
placebos are explored.
Avainsanat – Nyckelord – Keywords
Placebos ; Ethics, Clinical ; Physicians, Primary Care
Säilytyspaikka – Förvaringställe – Where deposited
E-Thesis
Muita tietoja – Övriga uppgifter – Additional informationiii.
TABLE OF CONTENTS
1 Introduction ..................................................................................................................................................... 1
2 Understanding placebos................................................................................................................................ 2
2.1 Definitions of placebo and related terms ....................................................................................... 2
2.2 Approaches to study placebos in a clinical setting ....................................................................... 4
3 Recent developments .................................................................................................................................... 5
3.1 Studies on the clinical use of placebos ............................................................................................ 5
3.2 Central findings ..................................................................................................................................... 7
4 Discussion ........................................................................................................................................................ 9
4.1 Issues........................................................................................................................................................ 9
4.2 Cognitive biases in clinical decision making ................................................................................ 10
4.3 Ethical concerns .................................................................................................................................. 11
4.4 Concluding remarks ........................................................................................................................... 12
References ................................................................................................................................................................ 13
Supplements ............................................................................................................................................................ 161 1 INTRODUCTION The idea that an academically trained healthcare professional might prescribe a placebo to their patient in order to alleviate their symptoms (if not cure them entirely) strikes many as absurd, bordering on quackery. The placebo is often understood in the context of the clinical trial, in which a sugar pill or a saline injection is pitted against a hopefully potent pharmacological agent. In this setting placebo is, quite literally, what we expect nothing of. However, multiple surveys of physicians around the world have found that a majority has employed what they perceive to be placebos in their clinical practice (1). What then is perceived as placebos within the clinical setting remains heterogeneous and vague. The aim of the present study was to examine the development in the understanding of placebos in the context of clinical practice in recent years. The paper was modelled after an earlier review, taking a similar conceptually oriented approach (2). The conceptual confusion related to the terms is deep-seated and uncertainty brands the entire field of placebo studies (3). In the beginning of this thesis a few of the different ways to define and understand placebos and placebo effects are described, providing some backdrop to the issues examined in the following chapters. Earlier approaches to study the prevalence of placebo use by doctors in the clinic are discussed briefly. Six recent empirical studies are reviewed: what have we learned of the clinical application of placebos within the past decade? Finally, the ethics of prescribing placebos as therapeutic agents is brought into focus. The encounter of the person in need of care and the professional provider of care, here referred to as the patient-provider relationship, is nowadays thought to be built on an honest exchange of information to respect a patient’s autonomy. An understanding of placebos that necessitates deception undermines this autonomy (4).
2 2 UNDERSTANDING PLACEBOS 2.1 Definitions of placebo and related terms To paraphrase Howard Brody, it is hard to define placebos without engaging in a small-scale project to reform modern medical thinking. Within the limited scope of this thesis it may be more helpful to instead describe a few different ways the word “placebo” is used in medical literature, showing how the definition is highly context-dependent. As such, it is difficult to define in a fashion that is practical in clinical use. In a linguistic approach, the word placebo can be used in three ways (5). Placebo as the component of a clinical trial. In this context, placebo is the null option where the bar is set for comparison. In practice, this requires merely the appearance of treatment to control for the effect of the intervention we are truly interested in. (5) Some authors differentiate this meaning by using the term “pure placebo”, leading to further confusion. Placebo as treatment. In questionnaires targeted to healthcare professionals, definitions of placebo in the clinical setting include some common criteria: 1) the aim to please the patient, 2) an intervention or a form of treatment that is perceived by the providing party as ineffectual or of no significant therapeutic value by itself, and 3) deception, which is not necessarily the concealment of the treatment’s true nature but may merely be the encouragement provided to the patient that the intervention will be beneficial for them. (5) The necessity of the deception aspect has been debated. It may be argued that ideally the entire therapeutic encounter incorporates reassurance that the patient will be helped, and this is seen as difficult to separate from the concept of the placebo (6). Sometimes falling under this umbrella of placebo-as-treatment are non-essential examination procedures, e.g. blood tests and X-rays, when these diagnostic tools are used to meet a patient’s demands or expectations and to cope with uncertainty rather than to aid in the formation of a diagnosis (7). Placebo as rapport. Here the terms placebo and placebo effect are used to refer to the beneficial effect inherent to a patient-provider relationship, requiring no conscious effort or conscious
3 acknowledgement from either party. It has been shown that a patient being unaware of being administered a painkiller impairs the effectiveness of the treatment (8). The terms “care effect” and “positive care effect” have been used to describe this type of beneficial effect inherent to any therapeutic encounter (9, 10). It is the second description, placebo-as-treatment, that a large portion of the conceptual confusion around placebos falls under. It encompasses both the classical pure placebo used in the strictest sense, similar to the trial context, as well as the huge variety of interventions known as “impure placebos” and “nonspecific methods”. The classic example is using antibiotics to treat what the clinician suspects to be a viral illness. In a recent focus group study addressing physician attitudes toward placebos in the US, one example given of an impure placebo was gabapentin, a commonly used medication for neurological pain, because of its debatable therapeutic benefits (6). In this sense, nearly anything existing within the scope of medicine could be deliberately applied as placebo, and what one doctor might consider evidence-based medicine another could regard as placebo. Use of ambiguous terms such as “impure placebo” remains a major methodological issue in modern placebo research (9). The large meta-ethnography by Hardman et al in 2020 describes the development of the definition in three steps, somewhat mirroring the linguistic approach: The original definition of placebos in modern medicine was a substance-forward one, originating from Henry Beecher, which developed in the direction of a process-forward definition as placebos were first examined through a meaning paradigm in the early 2000s (3). In recent years understanding of the term has evolved into a contextual definition that is seen related to setting (11) and patient characteristics (12) among other factors. Leaving the terminology altogether undefined can pose a problem just as an inadequate definition can distort the conversation. The disconnect between how placebos are understood in theory and in practice remains a central issue (3). Negative and positive connotations from the research context and the clinical context bleed into each other. Both
4 patients’ and clinicians’ attitudes toward placebos vary greatly, and not least because of the many explanations given to the concept. Indeed, the very way the question about the use of placebos is worded may distort the information we can glean from the respondent - the framing may be anything between positive and derogatory, rarely being completely neutral. The explicit use of the word placebo itself may change or compromise the results of a survey (13). 2.2 Approaches to study placebos in a clinical setting Quantitative studies on the practical application of placebos by doctors have sent out questionnaires along with a variety of definitions of the central concepts. The respondents are asked about prescribing, ordering or administering placebos, pure placebos, impure placebos, placebo treatments, non-specific therapies, sometimes with an open-ended question that allows the respondent to elaborate on their own definition of the subject. A standardised questionnaire has so far not been commonly accepted, each author developing or customising one for the purposes of their study. This impairs the consistency and comparability of the studies, as it can not be conclusively determined that the questionnaires actually measure the same thing (2). Depending on the definition of placebo, the prevalence of placebo use may vary between 12% and 97% within the same data set (7). These dramatic numbers often lead to flashy headlines in newspapers, as placebo’s negative connotation as “fake treatment” is allowed to capture the public imagination. The deliberate use of placebos has been studied in a controlled setting with so-called open- label placebos, meaning a physiologically and pharmacologically inert therapeutic agent that is presented to the patient as having a “non-specific effect” instead of a “specific effect” (14, 15). “Non-specific” here tends to carry the connotation of “mechanism that is not understood”, but is often not clearly defined. This framing has a positive connotation as it appears to remove the necessity of deceiving the patient.
5 3 RECENT DEVELOPMENTS 3.1 Studies on the clinical use of placebos In this narrative review, the aim was to critically examine empirical studies on placebo use in a clinical practice context, published within the past decade, and identify possible modern trends in the field. Studies were gathered primarily through Medline searches, detailed in Supplement 1, as well as key author searches through Medline and PubMed. Exclusively qualitative surveys concerning professional attitudes and quantitative surveys on patient views were excluded. Altogether 6 articles were identified, the earliest published in Poland in 2013 (12) and the latest in Australia in 2019 (16). The other studies were undertaken in the UK (7) Germany (17) Canada (18) and Portugal (19). Characteristics of the studies are provided in Supplement 2. In addition, a meta-analysis from 2018 (1) and a meta- ethnography from 2020 (3) were examined for their views on placebo research on a larger timescale. In the six studies, sample sizes ranged from 122 to 2018 practicing doctors, mostly general practitioners, but also including internal medicine specialists, rheumatologists, orthopaedic surgeons and paediatricians. The response rates varied between 9% for an online survey sent via email to a sample of 1543 Australian doctors (16) up to 78% for a sample of 220 Polish doctors all of whom were contacted personally (12). In two large sample size European studies the response rate averaged 46% (7, 17). The questionnaire forms and the definitions of the central concepts remain variable in the new studies. As a standardised survey instrument does not currently exist, all of the studies had either adapted a questionnaire from previous studies or developed one of their own. By far the most cited survey instrument was Nitzan and Lichtenberg’s questionnaire survey from 2004 (20). Both Bąbel and the Portuguese authors reported adapting exclusively this instrument for their use. Howick et al used an adapted questionnaire influenced by Nitzan and Lichtenberg, Hróbjartsson and Norup (21), Fässler et al (22), Sherman and Hickner (23), Tilburt et al (24), and Meissner et al (25). Faasse and Colagiuri based their survey instrument
6 on the questionnaire detailed by Howick. Harris et al used the American questionnaire detailed by Sherman and Hickner (23) to enable direct comparison of their data sets. Linde et al had earlier developed their own 50 item questionnaire, detailed comprehensively in a separate paper (26). In one study (12) the explicit use of the word ‘placebo’ was omitted from the survey form entirely, opting instead to refer to “nonspecific methods of treatment”. The definition given for this term was given as follows: “For our purposes, we construe nonspecific methods of treatment to be all the medical substances, practices, and procedures whose efficacy is difficult to prove scientifically, even though they might seem efficacious. These may be pharmacological treatments of both inactive types (e.g. sugar pills, injections of saline), and active types, where the latter are used in cases in which - at least theoretically - they should have no impact on the symptoms of a patient (as with antibiotics in the treatment of viral illnesses, or vitamins taken for fatigue). The same method which is specific when it is used in one case (e.g. antibiotics in the treatment of bacterial infection) may be nonspecific in other case (e.g. antibiotics in the treatment of viral illnesses). Frequently, methods from natural and/or alternative medicine (e.g. homeopathy and certain physiotherapeutic procedures) are considered to be examples of nonspecific methods of treatment: they happen to be effective, yet the mechanism of their operation is often impossible to explain scientifically.” (sic) Another study eschewed defining the term placebo entirely, instead relying on respondents’ self-reporting on treatments they themselves perceived as placebos (19). These extremely broad descriptions are deliberately open to interpretation. However, they render the survey instruments vulnerable to response bias. Four out of six studies retained some form of the pure-impure placebo dichotomy, contrasting the clinical trial equivalent with a large variety of therapeutic practices employed as placebos by the respondents. Two studies directly referred to the older convention of pure
7 and impure placebos, considering it pragmatic to also allow respondents to comment upon the accuracy of the terms. (7, 18) Howick et al also included the use of diagnostic measures, such as non-essential physiologic or technical examinations like blood tests and X-rays, as impure placebos. The German paper chose to separate placebos, limited to the strict clinical trial sense, from less accurately defined non-specific treatments (17). The methodological issues present with the use of ambiguous wording are acknowledged in all but one of the studies, the most recent one from Australia. In it, Faasse and Colagiuri introduce the terms “active placebo” and “inert placebo”. Active placebo was described as being “active treatments prescribed solely or primarily to enhance treatment outcomes by increasing positive expectations - rather than through any specific physiological or pharmacological treatment effect” and inert placebo as “like a sugar pill or saline injection that are prescribed to enhance patient expectations and improve outcomes via the placebo effect”. Interestingly, the most common “inert placebo” treatments prescribed were saline nasal spray and aqueous skin creams. (16) While intranasal saline is pharmacologically relatively inert, it also has a specific active effect in reducing nasal obstruction through diluting mucus and enhancing its flow. It can hardly be considered a classical “pure” placebo. The authors deliberately sought to highlight the conceptual overlap (16), but the methodological issues remain. As a result, the two categories can not be directly compared with similar categories in the other studies. 3.2 Central findings The use of “pure” placebos in the clinical trial sense remains rare. When such a category was specified separately, the percentage of respondents declaring their use within the past 12 months ranged from 12% up to 50%. However, it remains unclear how the respondents have interpreted the concept of placebos and whether they truly abide by the strict definition. Only Linde et al asked their participants specifically about prefabricated placebos; in their study 5% of respondents reported that they had prefabricated placebo tablets or “globules” in practice (17).
8 A majority of respondents across all studies profess to resorting to some variety of non- specific intervention or other methods that they themselves perceive as placebos. The most common interventions overall prescribed in this manner by clinicians were vitamin and mineral supplements. Concerningly, Faasse and Colagiuri discovered that within the Australian sample they had obtained the single most common intervention prescribed as a placebo was antibiotics, one in five doctors reporting doing so to treat what they believed to be a self-limiting viral illness (16). Cultural factors affect placebo use among doctors. As noted by Bąbel, Poland is one of very few developing countries with any data collected on placebo use (12). While only one respondent out of 171 reported the use of sugar pills in the course of treatment, a majority (56%) has either prescribed or recommended homeopathy to their patients. In this study, the most common reasons given for placebo use in general were “to supplement a specific method” (56%) and “to calm patients” (46%) (12). In the Canadian study that included a comparison to an earlier US survey, it was found that while the overall rate of prescribing placebo-like non-specific treatments was similar, Canadian physicians were less inclined to call it placebo use, preferring a vague description of treatments without expected, evidence- based efficacy. Physicians in the US were more inclined to tell their patient they were prescribing a medication rather than a placebo, with the opposite being true among Canadian physicians. The difference was speculated to stem from US physicians being more reserved to prescribe ineffective treatments openly, as medications and treatments in the US are generally more expensive. (18) Braga-Simões et al were interested in the correlation between placebo prescribing behaviour and practitioner characteristics. They utilized a version of the Jefferson Scale of Physician Empathy questionnaire translated to Portuguese along with their placebo use questionnaire. Interestingly, 43% of physicians responding to the questionnaire reported not offering any clarifying comment to the patient upon recommendation, perhaps reflecting a more paternalistic culture of care. Only 10% openly disclosed that they were prescribing a placebo.
9 In this study the most common reasons given for applying placebo treatments were “to calm the patient” (60%) and “to distinguish between real and imaginary symptoms or organic and psychological symptoms” (60%). Favourable attitudes toward placebo prescription and a higher rate of actual prescription were associated with a higher empathy score, as well as a younger age. (19) In the German study, the most common reasons given for applying these methods were a genuine belief that a beneficial effect would result, perceived pressure from the patient in the form of explicit demands or an unmet medical need, supplementing a specific method of treatment, and as a diagnostic tool (17). In the Canadian data set alone diagnostics were the most common reasoning given (18). The precise way in which the placebos aided in diagnosis was not elaborated upon. 4 DISCUSSION 4.1 Issues In each of the six studies either a unique definition of placebos is given or the authors rely entirely on the respondents’ interpretation of the questionnaire. While the findings indicate that the prevalence of the use of placebos in clinical practice is largely consistent between samples, the differences in methodology among the studies make rigorous numerical comparison of the data sets infeasible. In addition to heterogeneous definitions of the related terminology, cultural differences may explain parts of the differences observed. Paternalistic attitudes toward a physician’s authority and patient autonomy still affect modern medicine, particularly in developing countries (12, 27). The circumstances that motivate doctors to choose what they perceive as placebos to treat patients are complex. When asked to give reasons for prescribing placebos, a large number of doctors report genuinely believing a beneficial “placebo effect” would be obtained.
10 However, it may be that attempting to evoke a placebo effect is better characterized as an a posteriori justification rather than the initial reason for applying the treatment. (1) A fundamental conceptual difference between placebo use and something having a placebo effect has also been pointed out (2). The high-quality meta-analysis by Linde et al in 2018 posits that it may be inadequate or inappropriate to label the use of all above-mentioned non- specific interventions as use of placebos (1). While a deliberate attempt to harness a placebo effect through applying a non-essential medical procedure may be seen as placebo use, using a pharmacologically inert substance to aid in a differential diagnosis, as described by Harris et al, would not qualify as placebo use in the same sense. The large meta-ethnography by Hardman et al in 2020 appears to come to a similar conclusion, suggesting that in further research the concept of placebos in the clinical setting might be best abandoned entirely (3). 4.2 Cognitive biases in clinical decision making In the 1970s, cognitive biases were recognized to affect a clinical professional’s day-to-day decision making (28). Does a clinician’s willingness to apply placebos in their practice stem from a kind of cognitive bias? A certain extent of uncertainty is unavoidable in clinical work, especially in a primary care setting. The initial encounter with a patient is often brief, and there is rarely enough time or resources to fully form an accurate diagnosis and a treatment plan. “To calm the patient” appeared as an option on several of the questionnaires, with 30% to 60% of respondents reporting it as one of their reasons. Braga-Simões et al also found this to correlate with a higher empathy score using an adapted JSPE questionnaire, but also with a younger age of the practitioner (19). Is a more empathetic physician more inclined to try unconventional means to alleviate the patient’s anguish, or does it reflect a lack of experience in managing difficult clinical situations?
11 Commission bias is defined as resulting from the paternalistic obligation toward beneficence, in that harm to the patient can only be prevented by active intervention. In other words, it presents as a tendency toward action rather than inaction. (28) In a situation where time is limited, the patient’s complaint is non-specific, or the patient demands clinical examinations or treatments, the doctor may be inclined to employ non-specific treatments to ameliorate the patient’s concerns or to help with the diagnosis. 4.3 Ethical concerns Placebos may be seen as a threat toward modern views of patient autonomy. An implicit covenant of trust within the therapeutic encounter requires truthful and complete information transfer. (10) As a traditional understanding of clinical placebos has necessitated deception, the idea that placebos might be employed in clinical practice could be seen to erode the trust in the patient-provider relationship (4). In the Polish paper included in this study, a large number of respondents confessed to the use of placebo interventions in the guise of a specific method, when the use of the specific method could not be justified or could have harmed the patient (12). The role of information in the patient-provider relationship has become central, and both sides need to be able to make fully informed decisions. Blease et al pose the question: is a certain level of ambiguity or deception permissible and ethical, if the patient can genuinely benefit as a result? Are placebos fundamentally anti-autonomy? (10) What if a placebo could be prescribed to the patient with full transparency? One approach to alleviate ethical concern has been to study the effects of honestly prescribed placebos, also known as open-label placebos. The phenomenon is inherently challenging to study, as the administration of open-label placebos can not be meaningfully blinded (15). In a speech, Kaptchuk has suggested that if a patient’s pain could be reduced with the prescription of a pure placebo, the potentially harmful side effects of powerful painkillers could be avoided (29). An exploratory focus-group study conducted in the US found physician’s opinions divided. Open-label placebos were viewed both favourably and as disrespectful towards
12 patients, and the benefits were seen as questionable. (6) The line between a sound treatment option and quackery is viewed as thin. Open clinical placebo use probably remains far from becoming clinical reality. 4.4 Concluding remarks In conclusion, placebo in the context of a clinical trial has very little in common with placebo in the context of clinical practice. Prescribing any treatment that the clinician perceives to be a placebo appears to primarily be a strategy used by the clinician to cope with uncertainty and to better meet patient expectations and needs when strictly evidence-based means have proven inadequate or are otherwise not applicable (1,3). As reported by the respondents in these six studies, even certain evidence-based treatments such as neurological medications and technical diagnostic procedures that do not meet any widely accepted definition of the word placebo have been applied as such. While they are often described as attempts to harness the beneficial effect inherent to a patient-provider relationship after the fact, the reality of these decisions may be much more complicated. The widespread willingness to apply these methods to clinical practice may shed light to so far underappreciated aspects of medical education (16). Identifying and eliminating cognitive biases in clinical work may deserve stronger emphasis during the training of healthcare professionals. There remains a need for evidence-based guidelines on how to apply these “clinical management tools” to the benefit of the patient in an ethical, honest and structured manner (4, 30). Here, a further avenue of research is identified. Qualitative studies to address what types of management strategies clinicians use when confronted with uncertainty may be wise to avoid the confounding and suggestive terminology related to placebos altogether. As up- to-date medical knowledge disseminates more effectively through the internet and the mass media, patient understanding of treatment modalities increases (31). It is inevitable that patient attitudes toward individual treatments evolve as well and clinicians must adapt their choice of treatments as well as their words. As it has been recognized that shared medical decision making enhances the efficacy of treatments, clinicians continue to move forward
13
from a traditional, paternalistic approach to care (30). Honest and effective communication
is key to ensure informed co-operation between the doctor and the patient. The nature of
this communication also warrants further exploration.
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SUPPLEMENTS
SEARCH STRATEGY AND INCLUSION CRITERIA
In order to be selected for examination, the study had to meet the following criteria:
• English language full text available online.
• Published between February 2012 and February 2021. The earliest date was chosen to
avoid overlap with earlier work on a similar subject (2).
• Dealing with the results of questionnaires and surveys regarding the quantitative use and
prescription of placebos among primary care physicians, published as a scientific article in
peer-reviewed journals.
• Purely qualitative, open-ended questionnaires were excluded.
• Studies dealing primarily with patient views were excluded.
• Multiple likely relevant studies were identified, but had to be excluded for either being
unavailable in full form or having been written in German, French or Italian.
The search was conducted on OVID MEDLINE under the MeSH heading Placebos, combined
with the following subheadings over multiple cumulative searches:
“therapeutic use” “physicians, primary care” “administration and dosage”
The search strategy was supplemented with the following free-form searches using MEDLINE’s
Advanced Search function:
“open-label placebo” “placebos in clinical practice” “placebo prescription” “placebo, professional
use”
Additional articles were identified through key author searches (Linde K, Howick J)
Articles were first screened through by abstract only, and then screened for a second time by full
text, reading through them in chronological order.
In total, 6 studies published after 2012 were identified to meet the criteria.
Supplement 1. Search strategy and inclusion criteria.17
Source Country Participants (n) Methods Aims
1 Bąbel. Use of placebo interventions in primary care in Poland Internists (82) Quantitative survey To investigate the behavior, beliefs and attitudes of Polish
Poland. 2013 Family doctors (50) primary care physicians concerning the use of placebo
Pediatricians (55) interventions.
Two of the above (16)
2 Howick et al. Placebo use in the United Kingdom: UK General practitioners (783) Quantitative survey To find out the prevalence of placebo use in UK primary
Results from a national survey of primary care with open-ended care.
practitioners. 2014 questions
3 Linde et al. The use of placebo and non-specific Germany General practitioners (319) Quantitative survey To investigate the use of placebos and non-specific
therapies and their relation to basic professional attitudes Internists (311) treatments among German physicians and how their use is
and the use of complementary therapies among German Orthopaedists (305) associated with physician attitudes and beliefs.
physicians – A cross-sectional survey. 2014
4 Harris et al. Placebo Trends across the Border: US Canada Internists (198) Quantitative survey To investigate the use of placebos among Canadian
versus Canada. 2015 with optional open- physicians and to compare the results to US data obtained
ended questions with the same questionnaire.
5 Braga-Simões et al. Placebo prescription and empathy Portugal General practitioners (93) Quantitative survey To determine the frequency of placebo prescription, doctors’
of the physician: A cross-sectional study. 2017 with experimental beliefs, motivation, and attitudes to placebos in general
component practice in northern Portugal and to test the association
between placebo prescription and physician empathy.
6 Faasse and Colagiuri. Placebos in Australian general Australia General practitioners (136) Quantitative survey To examine rates of use and beliefs about placebos in
practice: A national survey of physician use, beliefs and with open-ended Australian general practice.
attitudes. 2019 questions
Supplement 2. Characteristics of included studies.You can also read
