Pediatricians’ approaches to communicating side effects

Pediatricians’ approaches to communicating side effects | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Pediatricians’ approaches to communicating side effects Anna de Geus, Dunya Seinen, Marc A. Benninga, Spin the General Pediatrics Research Network of the Dutch Association for Pediatrics, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7880572/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Purpose Most parents and adolescents want comprehensive information about potential side effects (SE) of medication. However, such information can sometimes trigger side effects due to negative expectations: the so-called nocebo effect. To develop evidence-based strategies that meet information needs while minimizing nocebo effects, this study examined how pediatricians currently communicate about side effects when prescribing medications. Methods A national multicenter survey among pediatricians and pediatric residents was performed. A nine-item questionnaire assessed education on SE communication, awareness of the nocebo effect, and communication about SE for ondansetron, inhaled steroids, and amoxicillin/clavulanic acid. Results A total of 438 respondents were included (80.1% pediatricians, 19.9% pediatric residents). Only 6.8% had received education on SE communication during medical school. The extent of information on SEs varied widely per medication type. Nearly half of the respondents (48.9%) never inquired about parents' or patients' informational needs on side effects. They were significantly more likely to never discuss side effects for all studied medications compared to those who did inquire needs. Awareness of the nocebo effect and its consideration in communication was reported by 41.3% of respondents. These respondents provided significantly more often minimal instead of extensive information compared to respondents not aware of the nocebo effect and/or not considering it in their communication. Conclusion There is substantial variability in pediatricians’ approaches to communicating SEs when prescribing medications, alongside a lack of education on this topic. These findings underscore the need for standardized, evidence-based guidelines and training supporting transparent communication while minimizing the nocebo effect. Nocebo side effects positive-framing medication information communication Figures Figure 1 What is known Poor adherence to treatment regimens is a major global problem, with side effects being an important contributor. The way physicians discuss potential side effects can itself influence the occurrence of side effects through the nocebo effect. What is new There is substantial variability among physicians in how side effects are communicated, depending on medication type, information framing, and tailoring to patients’ informational needs. Formal education on discussing side effects during medical school or postgraduate training is scarce among pediatricians and residents. Introduction Poor adherence to treatment regimens for chronic conditions is a global issue, contributing to negative health outcomes and increased financial pressure on healthcare systems [1]. One factor associated with non-adherence, is the occurrence of side effects (SE). The incidence of SE can be influenced by patient's expectations, patient-clinician relationship, and other contextual factors [2-6]. When negative expectations about an intervention, whether active or placebo, provoke adverse effects, this is referred to as the nocebo effect [6, 7]. Adult studies have shown that the incidence of SE increases when they are discussed beforehand,whereas omission of a particular side effect or positive framing can reduce its occurrence by 30 to 65% [2, 8-10]. Consequently, expert consensus recommends communicating about side effects in ways that minimize their induction [6]. This phenomenon is particularly relevant in pediatric healthcare, as children are naturally more suggestible than adults and more sensitive to the framing of treatment information [11]. Given the impact of negative expectations on the occurrence of SE and the potential benefits of positive framing, the way healthcare professionals communicate such information to children warrants careful consideration. A Dutch questionnaire study found that parents and teenagers prefer extensive and positively framed information on potential side effects, even after the nocebo effect was explained [12]. This underscores the importance of tailored communication strategies, as individual preferences vary. To develop evidence-based strategies that meet parents’ and patients’ informational needs while minimizing nocebo effects, it is essential to first understand how pediatricians communicate treatment-related risks. Therefore, the aim of this study was to explore the current approaches used by pediatricians in communicating side effects when prescribing medications. Methods Design, participants and setting This national, multicenter questionnaire survey targeted pediatricians and pediatric residents across the Netherlands. All hospitals in the Netherlands (both academic and non-academic) were contacted, and the invitation was disseminated internally within each hospital. Eligible participants were pediatricians and pediatric residents currently working in inpatient or outpatient pediatric care. Participation was voluntary and anonymous. Data were collected via a secure online platform during October and November 2024. Questionnaire The questionnaire was pilot tested among a small group of pediatricians (n=5) to ensure clarity and relevance prior to distribution. The questionnaire consisted of nine multiple-choice and open-ended questions addressing communication about SE. The questions assessed participant’s role, previous education on SE communication, awareness of the nocebo effect, as well as current communication strategies when prescribing ondansetron, inhaled corticosteroids, and amoxicillin/clavulanic acid. For each medication, participants selected one or more of eight predefined answer options ranging from ‘I discuss almost all side effects’ to ‘I almost never discuss side effects’ . The complete questionnaire is included in the Appendix. Statistical analysis This exploratory study aimed for a minimum sample size of 250 respondents. The data were manually restructured and coded. Categorical variables are reported as frequencies and percentages. Some response categories were dichotomized to ensure consistency and interpretability across analyses. Comparisons were made based on medication type, physician role (pediatrician vs. resident), hospital setting (academic vs. non-academic), physicians’ inquiry about side effect information needs, awareness of the nocebo effect, and prior education on SE communication. Group differences were examined using two-sided chi-square tests (α = 0.05). The analyses were primarily descriptive and exploratory, rather than focused on statistical significance. Data were analyzed using IBM SPSS Statistics version 30.0. Ethics and dissemination Ethical approval for this study was obtained from the Medical Ethics Committee of St. Antonius Hospital. Completion of the questionnaire was considered to imply informed consent. The study was conducted in accordance with the Declaration of Helsinki. Results Baseline characteristics A total of 438 respondents completed the questionnaire (Table 1), representing 53 hospitals, with most respondents from the Amsterdam university medical center (22.1%) and the university medical center of Utrecht (8.5%). Overall, 42.5% (n=186) were employed at academic hospitals, 54.8% (n=240) at non-academic hospitals, and for 2.7% (n=12) hospital type was missing. Threehundred-fifty-one (80.1%) were pediatricians and 87 respondents (19.9%) were pediatric residents. Regarding prior education on SE communication, 6.8% had received education during medical school, 55.5% had not received any education, and 37.7% were uncertain. Only 5.5% of pediatricians and residents had received post graduate education on this topic. No significant differences were found between pediatricians and pediatric residents. Communication approaches per medication type For ondansetron, 39.0% of respondents almost never discussed side effects, 26.9% shared minimal information about side effects, and 18.7% discussed only the serious but rare side effects (Figure 1a). For inhaled corticosteroids, 41.1% disclosed the common occurring side effects (> 10% incidence), 27.2% tailored information based on parental preferences, and 19.2% discussed the serious yet more rare side effects (Figure 1b). For amoxicillin/clavulanic acid, 68.9% of respondents disclosed the common side effects, 17.4% adjusted their response based on parental preferences, and 14.6% discussed all side effects with an incidence of >1% (Figure 1c). In contrast to ondansetron, only 9.4% and 10.5% of respondents almost never discussed side effects for inhaled steroids and amoxicillin/clavulanic acid, respectively (Figure 1). Inquiry into informational needs regarding side effects Of all respondents, approximately half of physicians (48.9%) never inquired about parents' and patients' informational needs on SE, 36.8% did so occasionally, and 14.4% almost always did. Pediatricians were significantly more likely to inquire about parents' or children's informational needs compared to pediatric residents (53.8% vs. 40.2%, p = 0.023, respectively). Physicians who did not inquire about these needs were significantly more likely to never discuss side effects for ondansetron, inhaled corticosteroids, and amoxicillin/clavulanic acid ( p < 0.001, p = 0.003, p < 0.001, respectively; Table 2). In addition, physicians who did not inquire about the needs, discussed long-term SE of inhaled corticosteroids significantly less than those who do inquire ( p = 0.028) and referred less to the patient information leaflet of amoxicillin/clavulanic acid ( p = 0.009). Awareness of the nocebo effect Overall, 41.3% of the respondents reported being aware of the nocebo effect and consistently considering it in their communication; 34.2% were sometimes aware of the nocebo effect; 10.3% were unaware of the effect and did not consider it; 8.0% were entirely unfamiliar with it; and 6.2% were aware but did not consider it in their communication (Table 3). Awareness of the nocebo effect was not significantly associated with prior education on discussing side effects nor with inquiring about parents or children’s informational needs (Table 3). Of all pediatricians, 77.8% reported being aware of the nocebo effect, compared to 66.7% of pediatric residents ( p = 0.031). Two patterns were observed regarding communication behaviors. First, physicians aware of the nocebo effect more often reported providing minimal SE information compared to physicians unaware of the nocebo effect and/or not considering it in their communication (ondansetron 31.4% vs. 13.1%, p < 0.001, inhaled steroids 14.2% vs. 6.5%, p = 0.036, amoxicillin/clavulanic acid 8.2% vs 1.9%, p = 0.023). Second, those unaware of the nocebo effect were more likely to report never discussing side effects, especially for ondansetron (54.2% vs. 34.1%, p < 0.001, respectively) and amoxicillin/clavulanic acid (15.9% vs. 8.8%, p = 0.037). Discussion This study aimed to explore current communication approaches employed by pediatricians and pediatric residents when discussing medication side effects with patients and their caregivers. Results showed a substantial variability in the extent to which SEs were communicated, which varied per medication type, the framing of the information, and whether the information was tailored to meet the informational needs of patients or their parents. Approximately half of the physicians indicated that they never inquire about parents' and patients' informational needs on SEs, and these physicians were more likely to omit disclosure of SE information. Notably, only 6.8% of participants reported having received formal education on this topic during medical school, and 5.5% during postgraduate training. Overall, awareness of the nocebo effect was limited (41.3%), and this awareness was associated with a tendency to provide limited information about SEs. In contrast, lack of awareness of the nocebo effect was more often linked to complete non-disclosure of SE information. The considerable variability observed in this study is not unexpected, given the absence of standardized approaches for communicating side effects and the limited education physicians receive on this topic. An international expert consensus with practical considerations for clinicians about placebo and nocebo effects has emphasized the importance of incorporating education on placebo and nocebo effects into medical training, highlighting their neurobiological and psychological mechanisms, and contextual and ethical considerations involved [6]. In addition, they also highlighted that communication should be tailored to individual patient needs. This aligns with previous findings showing that preferences for SE information vary widely: nearly half of adolescents and parents expressed a desire to be informed about all potential SEs, the other half preferred information restricted to common or clinically relevant SEs [12]. This does not reflect the current situation with over half of the respondents reporting that they never inquired about patients’ or parents’ informational needs and withheld or minimized SE information. Moreover, only 27% and 17% indicated that they adjusted the amount of side effect information according to parental preference when prescribing inhaled corticosteroids or amoxicillin/clavulanic acid, respectively. This reluctance to share extensive SE information may arise from physicians' beliefs that limiting disclosure is the most effective way to minimize nocebo effects. Clinicians might also fear that detailed disclosure could deter patients from taking the medications, as was reported by a focus group study among adult patients and clinicians [13]. The observation that informing patients about side effects increases their incidence, while many patients simultaneously prefer to receive extensive information, places physicians in a challenging position characterized by several dilemmas. First, this induces an ethical dilemma. On one hand, physicians have a responsibility to provide patients with sufficient information about adverse events to support informed decision-making and respect patient autonomy [7, 14, 15]. On the other hand, such disclosure on SEs may itself induce side effects, thereby potentially causing harm and conflicting with the principle of nonmaleficence. It could therefore be questioned whether providing comprehensive information is always in the patient’s best interests. Second, there is a legal dimension. Physicians are legally obliged to inform patients about adverse events and to obtain informed consent, although the exact regulations differ across countries. In the Netherlands, for example, this obligation is established in the Dutch Medical Treatment Agreement Act (WGBO). Article 7:448 of the Dutch Civil Code [16]. This Agreement Act requires physicians to inform patients about the proposed medical examination or treatment, its risks and consequences, alternatives options, and expected outcomes [16]. However, the law also leaves room for professional judgment, and the question remains how much detail is necessary and what is in the best interest of the patient’s health. Third, there are practical challenges. Comprehensive disclosure of all possible SEs can be time-consuming, particularly in busy outpatient settings. Explaining the nocebo effect and subsequently limiting discussion to severe adverse events might appear more efficient, yet this approach may also require additional time and skill. Consequently, physicians may prefer providing only brief information about the most common or severe SEs. In one study, a concise explanation of the nocebo effect did not reduce patients’ desire for extensive side effect information, whereas another study in adults using a more elaborate explanation did observe such an effect [12, 17]. These dilemma’s underscore the complexity of integrating nocebo-related communication strategies into clinical practice. Our study represents an important initial step toward developing standardized approaches communicating SEs. The international expert consensus recommends that “nocebo effects should be explained to patients and that information about side effects should be presented in such a way that nocebo effects are minimized” [6, 14]. Several practical considerations have been proposed to achieve this goal. One approach is positive framing of SE information (e.g. 70 % will not experience headaches, instead of 30% will experience headaches). Indeed, evidence in adults suggests that positively framed information can reduce the incidence of Ses [2, 8-10], but studies need to be performed in children as well. Another potential strategy to limit the nocebo effect and still maintain patients’ autonomy, is authorized concealment [18-21]. With this approach, patients engage in shared decision-making with the clinician to regulate the disclosure of side-effect information [15]. Adverse effects with the potential for serious or irreversible harm should not be concealed because patients cannot make informed choices without disclosure of serious risks. To date, there is no evidence on the effect of this intervention on the nocebo effect and it is even hypothesized that this approach could paradoxically induce a nocebo effect by drawing attention to undisclosed information and increasing patient curiosity [22]. This study has several strengths. To our knowledge, it is the first providing data on the communication strategies currently employed by pediatricians and pediatric residents when discussing SEs. Furthermore, the study includes a representative national cohort of Dutch pediatricians and pediatric residents, encompassing over 50 hospitals and nearly 450 physicians, thereby providing a robust overview of the variety in communication behaviors. Finally, the study draws attention to the gap between expert recommendations and clinical practice, particularly highlighting the huge variety in the way pediatricians discuss SE and the substantial lack of education and structural guidance on this topic. Several limitations should also be acknowledged. Although this study explored associations between education, awareness of the nocebo effect, and communication behavior, causal conclusions cannot be drawn. Additionally, as communication needs and preferences are influenced by social context and given that our study was conducted solely in the Netherlands, the generalizability of these findings to other countries may be limited. Finally, while participants were asked whether they were aware of the nocebo effect, we did not assess whether they fully understood its implications. Future research is needed to establish the effect of communication strategies on the nocebo effect and treatment adherence. Additionally, focus group studies involving pediatric patients and their caregivers could provide deeper insights into preferences and expectations regarding adverse event information. Such insights should be used to develop evidence-based guidelines for clinical practice, as well as evidence-based training programs for medical students and clinicians on how to communicate about nocebo effects and its effects on SE. In conclusion, this study demonstrates substantial variability in communication strategies employed by pediatricians and pediatric residents when discussing SEs and underscores the lack of formal education and guidance on this topic. Physicians should be encouraged to actively assess the informational needs of patients and caregivers, as these differ between individuals. There is a need for communication strategies that minimize the nocebo effect while preserving patient autonomy. Future research should focus on investigating such strategies and integrating them into both clinical practice and medical education. Abbreviations SE, side effect Declarations Funding The authors declare that no funds, grants, or other support were received during the preparation of this manuscript. Competing Interests MAB is consultant for Coloplast, Wellspect, Danone, Sensus, Cosun, FrieslandCampina, Cosun, Allergan, Abbott and Mallinckrodt. The other authors have no conflicts of interest to disclose. Author contributions Anna de Geus and Dunya Seinen carried out the analyses, drafted the initial manuscript, and revised the manuscript. Marc A. Benninga, participated in data collection and critically reviewed & revised the manuscript. SPIN, the General Pediatrics Research Network of the Dutch Association for Pediatrics critically reviewed the study protocol and coordinated data collection. Arine M. Vlieger conceptualized and designed the study, coordinated and supervised the process, critically reviewed and revised the manuscript. All authors read and approved the final manuscript. References WHO (2003) Adherence to long-term therapies: Evidence for action. World Health Organization, Genève. Webster RK, Rubin GJ (2021) Predicting Expectations of Side-Effects for Those Which Are Warned Versus Not Warned About in Patient Information Leaflets. 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Psychosom Med 73:598-603. https://doi.org/10.1097/PSY.0b013e3182294a50 Miller FG, Colloca L (2011) The placebo phenomenon and medical ethics: rethinking the relationship between informed consent and risk-benefit assessment. Theor Med Bioeth 32:229-243. https://doi.org/10.1007/s11017-011-9179-8 Blease C (2015) Authorized Concealment and Authorized Deception: Well-Intended Secrets Are Likely to Induce Nocebo Effects. Am J Bioeth 15:23-25. https://doi.org/10.1080/15265161.2015.1074310 Tables Tables 1 to 3 are available in the Supplementary Files section. Additional Declarations No competing interests reported. Supplementary Files Tables.docx Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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16:16:20","extension":"html","order_by":6,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":78689,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-7880572/v1/afe66b76281be60f7dfea1c8.html"},{"id":95567058,"identity":"2173566d-b319-42ee-87fd-445e7706136d","added_by":"auto","created_at":"2025-11-10 16:21:20","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":176408,"visible":true,"origin":"","legend":"\u003cp\u003eResponse distribution (%) for (a) ondansetron (b) inhaled steroids and (c) amoxicillin/clavulanic acid. \u003cbr\u003e\n SEs = side effects\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-7880572/v1/5829c0c9b4d3964787b7b2bf.png"},{"id":96454327,"identity":"0544cc87-8ed4-40f6-8c14-8e3cbacf4fcd","added_by":"auto","created_at":"2025-11-21 10:02:38","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":487872,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7880572/v1/725c62dc-8b64-4648-96b1-adc0654a8302.pdf"},{"id":95567057,"identity":"e1e00e1d-fd55-4463-bb67-dca02f565625","added_by":"auto","created_at":"2025-11-10 16:21:20","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":16896,"visible":true,"origin":"","legend":"","description":"","filename":"Tables.docx","url":"https://assets-eu.researchsquare.com/files/rs-7880572/v1/93b62096a916628926fd61b6.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Pediatricians’ approaches to communicating side effects","fulltext":[{"header":"What is known","content":"\u003cul\u003e\n \u003cli\u003ePoor adherence to treatment regimens is a major global problem, with side effects being an important contributor.\u003c/li\u003e\n \u003cli\u003eThe way physicians discuss potential side effects can itself influence the occurrence of side effects through the nocebo effect.\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003e\u003cstrong\u003eWhat is new\u003c/strong\u003e\u003c/p\u003e\n\u003cul\u003e\n \u003cli\u003eThere is substantial variability among physicians in how side effects are communicated, depending on medication type, information framing, and tailoring to patients’ informational needs.\u003c/li\u003e\n \u003cli\u003eFormal education on discussing side effects during medical school or postgraduate training is scarce among pediatricians and residents.\u003c/li\u003e\n\u003c/ul\u003e"},{"header":"Introduction","content":"\u003cp\u003ePoor adherence to treatment regimens for chronic conditions is a global issue, contributing to negative health outcomes and increased financial pressure on healthcare systems [1]. One factor associated with non-adherence, is the occurrence of side effects (SE). The incidence of SE can be influenced by patient's expectations, patient-clinician relationship, and other contextual factors [2-6]. When negative expectations about an intervention, whether active or placebo, provoke adverse effects, this is referred to as the nocebo effect [6, 7].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAdult studies have shown that the incidence of SE increases when they are discussed beforehand,whereas omission of a particular side effect or positive framing can reduce its occurrence by 30 to 65% [2, 8-10]. Consequently, expert consensus recommends communicating about side effects in ways that minimize their induction [6].\u003c/p\u003e\n\u003cp\u003eThis phenomenon is particularly relevant in pediatric healthcare, as children are naturally more suggestible than adults and more sensitive to the framing of treatment information [11]. Given the impact of negative expectations on the occurrence of SE and the potential benefits of positive framing, the way healthcare professionals communicate such information to children warrants careful consideration. A Dutch questionnaire study found that parents and teenagers prefer extensive and positively framed information on potential side effects, even after the nocebo effect was explained [12]. This underscores the importance of tailored communication strategies, as individual preferences vary. To develop evidence-based strategies that meet parents’ and patients’ informational needs while minimizing nocebo effects, it is essential to first understand how pediatricians communicate treatment-related risks. Therefore, the aim of this study was to explore the current approaches used by pediatricians in communicating side effects when prescribing medications.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003e\u003cem\u003eDesign, participants and setting\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThis national, multicenter questionnaire survey targeted pediatricians and pediatric residents across the Netherlands. All hospitals in the Netherlands (both academic and non-academic) were contacted, and the invitation was disseminated internally within each hospital. Eligible participants were pediatricians and pediatric residents currently working in inpatient or outpatient pediatric care. Participation was voluntary and anonymous. Data were collected via a secure online platform during October and November 2024.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eQuestionnaire\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThe questionnaire was pilot tested among a small group of pediatricians (n=5) to ensure clarity and relevance prior to distribution.\u003c/p\u003e\n\u003cp\u003eThe questionnaire consisted of nine multiple-choice and open-ended questions addressing communication about SE. The questions assessed participant’s role, previous education on SE communication, awareness of the nocebo effect, as well as current communication strategies when prescribing ondansetron, inhaled corticosteroids, and amoxicillin/clavulanic acid. For each medication, participants selected one or more of eight predefined answer options ranging from \u003cem\u003e‘I discuss almost all side effects’\u003c/em\u003e to \u003cem\u003e‘I almost never discuss side effects’\u003c/em\u003e. The complete questionnaire is included in the Appendix.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eStatistical analysis\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThis exploratory study aimed for a minimum sample size of 250 respondents. The data were manually restructured and coded. Categorical variables are reported as frequencies and percentages. Some response categories were dichotomized to ensure consistency and interpretability across analyses. Comparisons were made based on medication type, physician role (pediatrician vs. resident), hospital setting (academic vs. non-academic), physicians’ inquiry about side effect information needs, awareness of the nocebo effect, and prior education on SE communication. Group differences were examined using two-sided chi-square tests (α = 0.05). The analyses were primarily descriptive and exploratory, rather than focused on statistical significance.\u0026nbsp;Data were analyzed using IBM SPSS Statistics version 30.0.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eEthics and dissemination\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eEthical approval for this study was obtained from the Medical Ethics Committee of St. Antonius Hospital. Completion of the questionnaire was considered to imply informed consent. The study was conducted in accordance with the Declaration of Helsinki.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cem\u003eBaseline characteristics\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eA total of 438 respondents completed the questionnaire (Table 1), representing 53 hospitals, with most respondents from the Amsterdam university medical center (22.1%) and the university medical center of Utrecht (8.5%). Overall, 42.5% (n=186) were employed at academic hospitals, 54.8% (n=240) at non-academic hospitals, and for 2.7% (n=12) hospital type was missing. Threehundred-fifty-one (80.1%) were pediatricians and 87 respondents (19.9%) were pediatric residents. Regarding prior education on SE communication, 6.8% had received education during medical school, 55.5% had not received any education, and 37.7% were uncertain. Only 5.5% of pediatricians and residents had received post graduate education on this topic. No significant differences were found between pediatricians and pediatric residents.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eCommunication approaches per medication type\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eFor ondansetron, 39.0% of respondents almost never discussed side effects, 26.9% shared minimal information about side effects, and 18.7% discussed only the serious but rare side effects (Figure 1a). For inhaled corticosteroids, 41.1% disclosed the common occurring side effects (\u0026gt; 10% incidence), 27.2% tailored information based on parental preferences, and 19.2% discussed the serious yet more rare side effects (Figure 1b). For amoxicillin/clavulanic acid, 68.9% of respondents disclosed the common side effects, 17.4% adjusted their response based on parental preferences, and 14.6% discussed all side effects with an incidence of \u0026gt;1% (Figure 1c). In contrast to ondansetron, only 9.4% and 10.5% of respondents almost never discussed side effects for inhaled steroids and amoxicillin/clavulanic acid, respectively (Figure 1).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eInquiry into informational needs regarding side effects\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eOf all respondents, approximately half of physicians (48.9%) never inquired about parents' and patients' informational needs on SE, 36.8% did so occasionally, and 14.4% almost always did. Pediatricians were significantly more likely to inquire about parents' or children's informational needs compared to pediatric residents (53.8% vs. 40.2%, \u003cem\u003ep\u003c/em\u003e = 0.023, respectively). Physicians who did not inquire about these needs were significantly more likely to never discuss side effects for ondansetron, inhaled corticosteroids, and amoxicillin/clavulanic acid (\u003cem\u003ep\u003c/em\u003e \u0026lt; 0.001, \u003cem\u003ep\u003c/em\u003e = 0.003, \u003cem\u003ep\u003c/em\u003e \u0026lt; 0.001, respectively; Table 2). \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIn addition, physicians who did not inquire about the needs, discussed long-term SE of inhaled corticosteroids significantly less than those who do inquire (\u003cem\u003ep\u003c/em\u003e = 0.028) and referred less to the patient information leaflet of amoxicillin/clavulanic acid (\u003cem\u003ep\u003c/em\u003e = 0.009).\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eAwareness of the nocebo effect\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eOverall, 41.3% of the respondents reported being aware of the nocebo effect and consistently considering it in their communication; 34.2% were sometimes aware of the nocebo effect; 10.3% were unaware of the effect and did not consider it; 8.0% were entirely unfamiliar with it; and 6.2% were aware but did not consider it in their communication (Table 3). Awareness of the nocebo effect was not significantly associated with prior education on discussing side effects nor with inquiring about parents or children’s informational needs (Table 3). Of all pediatricians, 77.8% reported being aware of the nocebo effect, compared to 66.7% of pediatric residents (\u003cem\u003ep\u003c/em\u003e = 0.031). Two patterns were observed regarding communication behaviors. First, physicians aware of the nocebo effect more often reported providing minimal SE information compared to physicians unaware of the nocebo effect and/or not considering it in their communication (ondansetron 31.4% vs. 13.1%, \u003cem\u003ep\u003c/em\u003e \u0026lt; 0.001, inhaled steroids 14.2% vs. 6.5%, \u003cem\u003ep\u003c/em\u003e = 0.036, amoxicillin/clavulanic acid 8.2% vs 1.9%, \u003cem\u003ep\u0026nbsp;\u003c/em\u003e= 0.023). Second, those unaware of the nocebo effect were more likely to report never discussing side effects, especially for ondansetron (54.2% vs. 34.1%, \u003cem\u003ep\u003c/em\u003e \u0026lt; 0.001, respectively) and amoxicillin/clavulanic acid (15.9% vs. 8.8%, \u003cem\u003ep\u003c/em\u003e = 0.037).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis study aimed to explore current communication approaches employed by pediatricians and pediatric residents when discussing medication side effects with patients and their caregivers. Results showed a substantial variability in the extent to which SEs were communicated, which varied per medication type, the framing of the information, and whether the information was tailored to meet the informational needs of patients or their parents. Approximately half of the physicians indicated that they never inquire about parents' and patients' informational needs on SEs, and these physicians were more likely to omit disclosure of SE information. Notably, only 6.8% of participants reported having received formal education on this topic during medical school, and 5.5% during postgraduate training. Overall, awareness of the nocebo effect was limited (41.3%), and this awareness was associated with a tendency to provide limited information about SEs. In contrast, lack of awareness of the nocebo effect was more often linked to complete non-disclosure of SE information.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe considerable variability observed in this study is not unexpected, given the absence of standardized approaches for communicating side effects and the limited education physicians receive on this topic. An international expert consensus with practical considerations for clinicians about placebo and nocebo effects has emphasized the importance of incorporating education on placebo and nocebo effects into medical training, highlighting their neurobiological and psychological mechanisms, and contextual and ethical considerations involved [6]. In addition, they also highlighted that communication should be tailored to individual patient needs. This aligns with previous findings showing that preferences for SE information vary widely: nearly half of adolescents and parents expressed a desire to be informed about all potential SEs, the other half preferred information restricted to common or clinically relevant SEs [12]. This does not reflect the current situation with over half of the respondents reporting that they never inquired about patients’ or parents’ informational needs and withheld or minimized SE information. Moreover, only 27% and 17% indicated that they adjusted the amount of side effect information according to parental preference when prescribing inhaled corticosteroids or amoxicillin/clavulanic acid, respectively. This reluctance to share extensive SE information may arise from physicians' beliefs that limiting disclosure is the most effective way to minimize nocebo effects. Clinicians might also fear that detailed disclosure could deter patients from taking the medications, as was reported by a focus group study among adult patients and clinicians [13].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe observation that informing patients about side effects increases their incidence, while many patients simultaneously prefer to receive extensive information, places physicians in a challenging position characterized by several dilemmas. First, this induces an ethical dilemma. On one hand, physicians have a responsibility to provide patients with sufficient information about adverse events to support informed decision-making and respect patient autonomy [7, 14, 15]. On the other hand, such disclosure on SEs may itself induce side effects, thereby potentially causing harm and conflicting with the principle of nonmaleficence. It could therefore be questioned whether providing comprehensive information is always in the patient’s best interests. Second, there is a legal dimension. Physicians are legally obliged to inform patients about adverse events and to obtain informed consent, although the exact regulations differ across countries. In the Netherlands, for example, this obligation is established in the Dutch Medical Treatment Agreement Act (WGBO). Article 7:448 of the Dutch Civil Code [16]. This Agreement Act requires physicians to inform patients about the proposed medical examination or treatment, its risks and consequences, alternatives options, and expected outcomes [16]. However, the law also leaves room for professional judgment, and the question remains how much detail is necessary and what is in the best interest of the patient’s health. Third, there are practical challenges. Comprehensive disclosure of all possible SEs can be time-consuming, particularly in busy outpatient settings. Explaining the nocebo effect and subsequently limiting discussion to severe adverse events might appear more efficient, yet this approach may also require additional time and skill. Consequently, physicians may prefer providing only brief information about the most common or severe SEs. In one study, a concise explanation of the nocebo effect did not reduce patients’ desire for extensive side effect information, whereas another study in adults using a more elaborate explanation did observe such an effect [12, 17].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThese dilemma’s underscore the complexity of integrating nocebo-related communication strategies into clinical practice. Our study represents an important initial step toward developing standardized approaches communicating SEs. The international expert consensus recommends that “nocebo effects should be explained to patients and that information about side effects should be presented in such a way that nocebo effects are minimized” [6, 14]. Several practical considerations have been proposed to achieve this goal. One approach is positive framing of SE information (e.g. 70 % will not experience headaches, instead of 30% will experience headaches). Indeed, evidence in adults suggests that positively framed information can reduce the incidence of Ses [2, 8-10], but studies need to be performed in children as well. Another potential strategy to limit the nocebo effect and still maintain patients’ autonomy, is authorized concealment [18-21]. With this approach, patients engage in shared decision-making with the clinician to regulate the disclosure of side-effect information [15]. Adverse effects with the potential for serious or irreversible harm should not be concealed because patients cannot make informed choices without disclosure of serious risks. To date, there is no evidence on the effect of this intervention on the nocebo effect and it is even hypothesized that this approach could paradoxically induce a nocebo effect by drawing attention to undisclosed information and increasing patient curiosity [22].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThis study has several strengths. To our knowledge, it is the first providing data on the communication strategies currently employed by pediatricians and pediatric residents when discussing SEs. Furthermore, the study includes a representative national cohort of Dutch pediatricians and pediatric residents, encompassing over 50 hospitals and nearly 450 physicians, thereby providing a robust overview of the variety in communication behaviors. Finally, the study draws attention to the gap between expert recommendations and clinical practice, particularly highlighting the huge variety in the way pediatricians discuss SE and the substantial lack of education and structural guidance on this topic.\u003c/p\u003e\n\u003cp\u003eSeveral limitations should also be acknowledged. Although this study explored associations between education, awareness of the nocebo effect, and communication behavior, causal conclusions cannot be drawn. Additionally, as communication needs and preferences are influenced by social context and given that our study was conducted solely in the Netherlands, the generalizability of these findings to other countries may be limited. Finally, while participants were asked whether they were aware of the nocebo effect, we did not assess whether they fully understood its implications.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eFuture research is needed to establish the effect of communication strategies on the nocebo effect and treatment adherence. Additionally, focus group studies involving pediatric patients and their caregivers could provide deeper insights into preferences and expectations regarding adverse event information. Such insights should be used to develop evidence-based guidelines for clinical practice, as well as evidence-based training programs for medical students and clinicians on how to communicate about nocebo effects and its effects on SE.\u003c/p\u003e\n\u003cp\u003eIn conclusion, this study demonstrates substantial variability in communication strategies employed by pediatricians and pediatric residents when discussing SEs and underscores the lack of formal education and guidance on this topic. Physicians should be encouraged to actively assess the informational needs of patients and caregivers, as these differ between individuals. There is a need for communication strategies that minimize the nocebo effect while preserving patient autonomy. Future research should focus on investigating such strategies and integrating them into both clinical practice and medical education.\u0026nbsp;\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003e\u003cem\u003eSE,\u003c/em\u003e side effect\u0026nbsp;\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that no funds, grants, or other support were received during the preparation of this manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting Interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eMAB is consultant for Coloplast, Wellspect, Danone, Sensus, Cosun, FrieslandCampina, Cosun, Allergan, Abbott and Mallinckrodt. The other authors have no conflicts of interest to disclose.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAnna de Geus and Dunya Seinen carried out the analyses, drafted the initial manuscript, and revised the manuscript. \u0026nbsp;Marc A. Benninga, participated in data collection and critically reviewed \u0026amp; revised the manuscript. SPIN,\u0026nbsp;the General Pediatrics Research Network of the Dutch Association for Pediatrics\u0026nbsp;critically reviewed the study protocol and coordinated data collection. Arine M. Vlieger conceptualized and designed the study, coordinated and supervised the process, critically reviewed and revised the manuscript.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAll authors read and approved the final manuscript.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eWHO (2003) Adherence to long-term therapies: Evidence for action. 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Focus group study of patient and clinician perspectives. Can Fam Physician 48:104-110. \u003c/li\u003e\n\u003cli\u003eEvers AWM, Colloca L, Blease C, Annoni M, Atlas LY, Benedetti F, Bingel U, et al. (2018) Implications of Placebo and Nocebo Effects for Clinical Practice: Expert Consensus. Psychother Psychosom 87:204-210. https://doi.org/10.1159/000490354\u003c/li\u003e\n\u003cli\u003eColloca L (2017) Tell Me the Truth and I Will Not Be Harmed: Informed Consents and Nocebo Effects. Am J Bioeth 17:46-48. https://doi.org/10.1080/15265161.2017.1314057\u003c/li\u003e\n\u003cli\u003eDutch Civil Code Book 7 (Burgerlijk Wetboek Boek 7). https://wetten.overheid.nl/BWBR0005290. April 2025\u003c/li\u003e\n\u003cli\u003eNestoriuc Y, Pan Y, Kinitz T, Weik E, Shedden-Mora MC (2021) Informing About the Nocebo Effect Affects Patients\u0026apos; Need for Information About Antidepressants-An Experimental Online Study. Front Psychiatry 12:587122. https://doi.org/10.3389/fpsyt.2021.587122\u003c/li\u003e\n\u003cli\u003eGeers AL, Spotts EK, Vang M, Mayer SR, Miller FG (2023) The Use of Authorized Concealment to Minimize Nocebo Side Effects: A Survey of US Public Attitudes. Psychother Psychosom 92:391-398. https://doi.org/10.1159/000535011\u003c/li\u003e\n\u003cli\u003eSpotts EK, Miller FG, Geers AL (2025) Individual difference factors that predict evaluations and acceptance of authorized concealment for the reduction of nocebo side effects. Patient Educ Couns 134:108676. https://doi.org/10.1016/j.pec.2025.108676\u003c/li\u003e\n\u003cli\u003eColloca L, Miller FG (2011) The nocebo effect and its relevance for clinical practice. Psychosom Med 73:598-603. https://doi.org/10.1097/PSY.0b013e3182294a50\u003c/li\u003e\n\u003cli\u003eMiller FG, Colloca L (2011) The placebo phenomenon and medical ethics: rethinking the relationship between informed consent and risk-benefit assessment. Theor Med Bioeth 32:229-243. https://doi.org/10.1007/s11017-011-9179-8\u003c/li\u003e\n\u003cli\u003eBlease C (2015) Authorized Concealment and Authorized Deception: Well-Intended Secrets Are Likely to Induce Nocebo Effects. Am J Bioeth 15:23-25. https://doi.org/10.1080/15265161.2015.1074310\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTables 1 to 3 are available in the Supplementary Files section.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Nocebo, side effects, positive-framing, medication information, communication","lastPublishedDoi":"10.21203/rs.3.rs-7880572/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7880572/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003ePurpose\u003c/h2\u003e\u003cp\u003eMost parents and adolescents want comprehensive information about potential side effects (SE) of medication. However, such information can sometimes trigger side effects due to negative expectations: the so-called nocebo effect. To develop evidence-based strategies that meet information needs while minimizing nocebo effects, this study examined how pediatricians currently communicate about side effects when prescribing medications.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003eA national multicenter survey among pediatricians and pediatric residents was performed. A nine-item questionnaire assessed education on SE communication, awareness of the nocebo effect, and communication about SE for ondansetron, inhaled steroids, and amoxicillin/clavulanic acid.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eA total of 438 respondents were included (80.1% pediatricians, 19.9% pediatric residents). Only 6.8% had received education on SE communication during medical school. The extent of information on SEs varied widely per medication type. Nearly half of the respondents (48.9%) never inquired about parents' or patients' informational needs on side effects. They were significantly more likely to never discuss side effects for all studied medications compared to those who did inquire needs. Awareness of the nocebo effect and its consideration in communication was reported by 41.3% of respondents. These respondents provided significantly more often minimal instead of extensive information compared to respondents not aware of the nocebo effect and/or not considering it in their communication.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e\u003cp\u003eThere is substantial variability in pediatricians\u0026rsquo; approaches to communicating SEs when prescribing medications, alongside a lack of education on this topic. These findings underscore the need for standardized, evidence-based guidelines and training supporting transparent communication while minimizing the nocebo effect.\u003c/p\u003e","manuscriptTitle":"Pediatricians’ approaches to communicating side effects","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-11-10 16:21:15","doi":"10.21203/rs.3.rs-7880572/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"8d04d157-d25f-4175-8087-0f8b509f8532","owner":[],"postedDate":"November 10th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-12-06T16:23:17+00:00","versionOfRecord":[],"versionCreatedAt":"2025-11-10 16:21:15","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7880572","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7880572","identity":"rs-7880572","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}