Patient attitudes towards side effect information: An important foundation for the ethical discussion of the nocebo effect of informed consent

Abstract

A growing body of evidence suggests that the informed consent process, in which patients are warned about potential side effects of a treatment, can trigger a nocebo effect where expectations about side effects increase side effect occurrence. This has sparked an ethical debate about how much information patients ought to receive before a treatment while trying to balance the moral principles of patient autonomy and nonmaleficence. In keeping with the principle of patient autonomy, the opinion of patients themselves in relation to how much information they want about side effects is of utmost relevance in this debate. The literature was searched to identify surveys assessing patient attitudes towards side effect information. Across a broad variety of patient populations, treatment types, and countries, the majority of patients wished to be fully informed of potential side effects, particularly in relation to frequent and severe side effects, while only a small minority wanted minimal or no information at all. Results from this review suggest that nocebo research should focus on methods of avoiding nocebo effects of informed consent while ensuring that patients are well-informed about potential side effects.

Keywords

Health care informed consent truth disclosure

Background

The informed consent process, in which patients are warned about potential side effects of a treatment, is an important pillar in the patient–clinician relationship.¹ The previously paternalistic view, where treatment decisions were left to the clinician, has been overtaken by the principle of patient autonomy, where the patient should be fully informed about the treatment, including potential side effects, to be able to make an informed treatment decision.² However, a growing body of evidence coming from the field of nocebo research suggests that information about potential side effects in itself can increase the risk of side effect occurrence,³ a phenomenon called the nocebo effect.⁴ Meta-analyses of randomised controlled trials carried out across a multitude of different treatments and conditions show that placebo-treated patients experience similar types and proportions of side effects as those treated with an active treatment.⁵ This suggests that the informed consent process, which is identical for placebo and active treatment groups, may influence side effect occurrence. In support, direct experimental evidence shows that omitting versus disclosing information about potential side effects reduces versus increases the risk of side effect occurrence.³ Thus, by respecting patient autonomy and disclosing information about potential side effects, the clinician may inadvertently increase the patient’s risk of experiencing those side effects. This violates the principle of nonmaleficence, which states that a clinician should never inflict unnecessary harm on a patient.⁶ This conflict between autonomy and nonmaleficence is sometimes referred to as the ethical dilemma of the nocebo effect of informed consent.⁷ How to balance the moral principles of patient autonomy and nonmaleficence, and what information to disclose under which circumstances, is a widely discussed topic among experts.^8–13 However, in keeping with the principle of patient autonomy, the opinion of patients themselves in relation to how much information they want about side effects is of utmost relevance in this debate. Therefore, the aim of this article was to review evidence from patient surveys exploring attitudes towards side effect information.

Literature search

Surveys assessing patient attitudes towards side effect information were identified by searching PubMed for key terms related to ‘informed consent’, ‘side effects’, and ‘survey’, and by checking reference lists and forward citations of relevant surveys. This was not meant as an exhaustive systematic review, but rather a brief overview seeking to cover a range of patient groups, treatment types, and countries. Sixteen studies were identified, assessing 7295 (mean = 456, range = 41–2500) patients’ attitudes towards information about potential side effects. Table 1 summarises survey characteristics. The surveys were conducted in the United Kingdom, the United States, Canada, Germany, Ethiopia, and Korea. A range of treatments and conditions were covered, including cancer, heart surgery, hip/knee surgery, ear/nose/throat surgery, emergency oral surgery, general day surgery, and gastrointestinal problems, as well as different types of populations including in-/outpatients, patients taking medicines, college students, and members of the general public. Some surveys additionally reported clinician attitudes towards side effect information.

Table 1.

Characteristics of included studies.

First author (year)	Country	Population	N (% females)	Mean (M) age or largest age group (%)
Barnet (2004)	UK	Cancer patients	82 (54%)	M = 66.7 years
Beresford (2001)	UK	Heart patients	50 (26%)	M = 62.7 years
Berhane (2013)	Ethiopia	Hospital in-/outpatients	384 (32%)	15–30 years (67%)
Chandrasenan (2007)	UK	Patients from hip and knee arthroplasty unit	100 (61%)	60–80 years (42%)
Dawes (1994)	UK	Ear/nose/throat patients	50 (–)	M = 41 years
Degerliyurt (2010)	US	Patients about to undergo emergency oral surgery	212 (56%)	M = 35.7 years
El-Wakeel (2006)	UK	Gastrointestinal patients	77 (52%)	M = 48.8 years
Jenkins (2001)	UK	Cancer patients	2331 (62%)	51–70 years (46%)
Kastanias (2009)	Canada	General day surgery patients	150 (47%)	M = 52.7 years
Keown (1984)	US	College students	35 (32%)	M = 19 years
Keown (1984)	US	Members of the general public	42 (61%)	M = 34 years
Kusch (2021	Germany	Regular users of medicine	41 (78%)	M = 44.9 years
Meredith (1996)	UK	Cancer patients	250 (49%)	15–64 years (56%)
Nair (2002)	Canada	Patients, who has taken/takes at least one medication	88 (75%)	M = 54 years
Shin (2015)	Korea	Cancer patients currently receiving treatment or follow-up	725 (55%)	M = 60.2 years
Tarn (2015)	US	Patients from senior centres	178 (74%)	M = 72.4 years
Ziegler (2001)	US	Patients visiting outpatient clinics, accompanying family members, medical students, nonprofessional employees	2500 (61%)	M = 47.2 years

UK: United Kingdom; US: United States.

The review consists of two main sections concurrently presenting and discussing findings from the included surveys and related literature: the first section assesses survey results on attitudes towards side effect information, covering patient attitudes and clinician attitudes. The second section considers potential predictors of patient attitudes towards side effect information. This covers patient characteristics as reported in the included surveys, and survey characteristics discussing the influence of risk descriptors. Last, this information is put into the context of the ethical dilemma of the nocebo effect of informed consent.

Attitudes towards side effect information

Patient attitudes towards side effect information

Overall, the majority of patients find information about side effects to be very important. In a focus group study exploring what patients want to know about their medications,¹⁴ proper information about side effects was a central theme, and patients generally agreed that full and detailed information about side effects was vital. Additionally, patients found it of great importance that a physician discussed potential side effects with the patient,¹⁵ and patients agreed that it was their right to be given detailed information about side effects.¹⁶ In line with this, 83% of patients found information about side effects ‘relevant’ or ‘very relevant’ (42.4% and 40.6%, respectively).¹⁷ Two surveys found that 60% and 73% ‘absolutely needed to know’ about all side effects, with an additional 37% and 21% indicating that they ‘would like to know’ about all side effects, respectively.^18,19 Across most of the surveys, the majority of patients wanted to know about all possible side effects,^16,18–23 although a few exceptions appeared. In one survey, only 38% wanted information about all side effects.²⁴ Furthermore, while another survey did not report how many patients wanted information about all side effects, it found that only 26% wanted to know about 10 risks or more.²⁵ A third study even found that only 4% thought that a doctor should discuss all side effects.¹⁵

Yet, although most patients generally wanted information about all side effects, there was a tendency to prioritise information about frequent and severe side effects over the rare and mild. In one survey, patients felt that information about severe side effects was more important than information about mild side effects.¹⁶ When patients had to rate the importance of information about side effects (‘0 = not important at all’; ‘100 = extremely important’), the average response was 84 and 63 for major and minor side effects, respectively,²⁶ similarly implying that information about severe side effects was more important than mild side effects. Likewise, a survey found that 44% wanted to be informed of a severe very rare side effect, and only 28% of a mild very rare side effect.²⁷ However, the same survey found that almost half (49%) wanted the same amount of information regardless of severity, and a minority (7%) wanted less information as severity increased. In terms of frequency, one survey found that patients either wanted to know all or nothing about potential side effects, regardless of frequency.²⁵ Two other surveys, however, found that more patients wanted to know about frequent side effects, although a majority still wanted to know about the rarer ones as well.^20,21 Furthermore, 49% of patients agreed that a doctor should discuss both frequent and severe side effects.¹⁵ Thus, although the majority of patients want to be informed about all potential side effects, it does seem that information about severe and frequent side effects is particularly important. Interestingly, a recent study showed that most patients initially expressed wanting to know about all side effects regardless of frequency or severity, yet when presented with this detailed risk information, patients often reconsidered and mainly wanted to know about severe and frequent side effects.²⁸

Additionally, even though on average the majority of patients want a lot of information about side effects, there is a large variation in what patients want to know and how important they find side effect information. This is evident in the survey where patients rated the importance of knowing about side effects (‘0 = not at all important’; ‘100 = extremely important’), where the range was 1–100 and 0–100 for major and minor side effects, respectively.²⁶ Thus, at least some patients found information about side effects to be ‘not important at all’. Furthermore, a consistent minority, averaging around 10% (ranging from 0.4% to 42%) does not want any information about side effects.^{15,16,19–21,23–25} One reason for patients wanting no or little information about side effects seemed to be that ‘ignorance is bliss’.²⁵

Findings are mixed as to whether patients are satisfied with the amount of information they receive about side effects. In a focus group study, patients expressed not being satisfied with the amount and quality of information that clinicians provided about side effects.¹⁴ A survey, however, found that the majority of patients (88%) were satisfied with the amount of information they received, while only a minority (10%) felt they had received too little information.²⁴ Similar views were found in another survey, where 74% felt they had received sufficient information about potential side effects.¹⁶

Clinician attitudes towards side effect information

Clinicians generally expressed that the disclosure of side effect information should depend on frequency and severity,^15,16,29 and only a minority thought that patients should know about mild side effects.¹⁶ This is somewhat in agreement with patients' tendency to find information about frequent and severe side effects particularly important, although a majority of patients still wanted to know about rare and mild side effects.

Clinicians’ top reasons for withholding information were (1) infrequency of the side effect and (2) a belief that too much information could cause unnecessary anxiety.³⁰ Clinicians generally agreed that too much information about side effects could be harmful to the patients.^14,16,30 From a patient point-of-view, 33% of patients indeed agreed that an information sheet would be anxiety provoking.²⁴ On the other hand, 57% of patients felt that information would be reassuring,²⁴ and patients disagreed that detailed information about potential side effects would increase anxiety.¹⁶ Furthermore, one survey found that patients who were worried about side effects also tended to want more information about side effects.¹⁵ Thus, there seems to be a discrepancy between clinician and patient opinions in terms of how information about side effects affects the patient.

Patients and clinicians also disagreed about patients’ abilities to make an informed treatment decision by weighing up information about benefits and potential side effects, with patients believing more in own abilities than physicians believed in patients’ abilities.¹⁶ This may be a contributing factor to why clinicians in a focus group study expressed that it would be appropriate for the clinicians themselves to decide how much each patient needed to know about side effects.¹⁴ Patients do not necessarily share this view; in a patient survey, 68% of patients expressed that clinicians should give the same information to all patients, while only 32% thought that the doctor should give as much information as they see fit.²³ Additionally, 73% of patients felt that clinicians should never withhold information,²³ indirectly suggesting that clinicians should disclose everything.

In summary, these surveys suggest that the majority of patients require lots of information, some particularly in relation to frequent and severe side effects, and a minority wants no information at all. Clinicians tend to think that too much information may be harmful and disclose the information they think is necessary and that the patient can handle. Although patients think that clinicians should not withhold information, patients are also generally happy with the amount of information they receive. In reality, patients may not understand what it entails to receive information about all potential side effects. This will be further addressed in the following section.

Predictors of patient attitudes towards side effect information

Patient characteristics as predictors of attitudes towards side effect information

Some surveys have investigated patient characteristics that may differentiate between and identify those patients who want to know a lot about side effects and those who want little or no information. In short, no clear patterns emerge. Most surveys find no gender differences,^{18,22,25–27} although one found that slightly more men than women (93% vs. 84%) wanted to know about the risk of nerve damage,²¹ and another that older women wanted maximum side effect information.²³ Regarding age differences, some surveys find that younger patients require more^18,27 and some less²³ side effect information than older patients, and yet others find no association between age and information need at all.^{21,22,24–26} For education level and social class, results are likewise mixed. One survey found that individuals with higher education wanted less information about side effects,²³ similar to another survey showing that college students wanted less information than the general public,²⁹ while some surveys found no associations.^24,26,27

Knowing that information about side effects may increase side effects occurrence (knowledge of the nocebo effect) could in theory influence attitudes towards side effect information. This is supported by a recent study showing that an online intervention briefly describing the nocebo phenomenon decreased desire for side effect information in relation to antidepressants.³¹ None of the included surveys report having informed patients about the nocebo effect nor report whether patients knew that information about side effects could increase side effect occurrence. One survey, though, asked patients and clinicians whether detailed explanation about potential side effects could make the patient more sensitive to side effects, to which clinicians tended to agree slightly more than patients.¹⁶ If patients are generally unaware that side effect information may increase the risk of side effect occurrence, then responses are likely to be skewed in favour of wanting more information. Future surveys may assess how patients’ knowledge about the nocebo effect influences desire for side effect information or alternatively inform patients about the nocebo effect prior to asking about information wishes.

Based on the included surveys, there is no compelling evidence of particular patient characteristics being strong predictors of patient information needs. For the time being, it seems the best way to predict patients’ attitudes towards side effect information is simply to ask them. However, the following section explores how survey characteristics may influence, and potentially bias, attitudes towards side effect information.

Survey characteristics as predictors of attitudes towards side effect information

The surveys vary in the wording of answer options, which may influence responses. Some surveys use qualitative risk descriptions (e.g. common, important, and major/minor)^{15,20–22,24,26} and others quantitative (e.g. >1:100, 1 in 10).^16,20,21,25 One survey combined these within the same answer option (e.g. ‘it occurs in a minority (e.g. 1 in 10 patients) (10%)’),²⁷ and another mixed qualitative and quantitative risk descriptions between answers options.²³ A survey’s choice of risk descriptions for answer options, whether purely qualitative, quantitative, or a combination/mix, may heavily influence patients’ responses. It is being debated which type of risk description is more appropriate. When asked, 42% of patients preferred quantitative risk descriptions (e.g. x occurs in 1:1000), 36% simply wanted to know about potential side effects without any frequency description (e.g. x may occur), and 23% preferred qualitative descriptions of relative frequencies (e.g. x occurs frequently/rarely).¹⁶ A systematic review reported a tendency to overestimate both qualitative and quantitative risk descriptions,³² supported by a survey which found that the general public overestimated the seriousness of side effects compared to clinicians.²⁹ A randomised controlled trial found that subjects had similar understandings of different types of risk descriptions (quantitative vs. combination), but only 44% to 66% adequately understood risk descriptions in general.³³ If patients do not adequately understand risk descriptions, then estimations of attitudes towards side effect information could be unreliable.

Along similar lines, many of the surveys had the answer option of wanting to know about ‘all’ side effects. Some patients may choose this option without fully grasping what ‘all information’ entails.²³ It may be the case for some patients at least that they do not want fully detailed information down to the mildest, most infrequent side effect, but want to be well-informed and do not want the clinician to withhold important information. In support of this, one survey found that more patients wanted to know about the important complications (44%) than all complications (38%).²⁴ Similarly, another survey found that although the majority still wanted to know about all side effects (77%), more wanted to know about the most common side effects (94%).²⁰ Further, another survey found that a smaller majority compared to other surveys (57%) wanted to know about all side effects and a relatively large proportion (33%) only wanted information about the most common.²¹ This is in great contrast to for example one survey where a large majority (above 80%) wanted to know about a side effect even if its frequency risk was <1:100,000.¹⁶ Interestingly, in the same survey, 74% of patients felt they had received adequate information about side effects, however, only 39% of clinicians felt that they had provided sufficient information. This supports the idea that some surveys may be overestimating how much information patients want, yet patients are nonetheless against nondisclosure and generally seem to want to be well-informed about potential side effects.

Conclusion and implications for future research

The diversity in the identified surveys allowed a general overview of attitudes towards side effect information in different patient populations across a number of different countries, and in relation to different types of conditions and treatments. While a consistent minority prefers not to receive any information, the majority of patients requires all or highly detailed information about potential side effects. There is no clear evidence that the level of information required depends on certain patient characteristics (e.g. age, gender, and education level). Clinicians feel that too much information about side effects may harm the patient and induce anxiety, and they find it appropriate to tailor information to each individual patient’s needs, meaning not necessarily disclosing all information about side effects. Patients, on the other hand, generally thought that it was never appropriate for a clinician to withhold information and that all patients should be provided with the same information. Despite this discrepancy in patient and clinician attitudes, patients are nevertheless mostly satisfied with the amount of information they receive. This is an indication that surveys may be overestimating the amount of side effect information patients actually want. Patients may judge side effects to be more common or more severe than they actually are, and when presented with fully detailed side effect information, evidence suggests that many may reconsider what they indeed want to know about side effects. Nonetheless, it is clear that patients want to be well-informed of the important side effects, with only a small minority wanting minimal information or no information at all.

This knowledge is important in the debate of how patients should be informed about side effects and lends support to the view that omitting side effects information to avoid nocebo effects is unethical. Research and discussions in this area should start from patients’ information wishes and work on a solution from there. Thus, future research should focus on methods of mitigating nocebo effects of informed consent while still ensuring that patients are well-informed about potential side effects. Furthermore, the potentially moderating effect of nocebo knowledge on attitudes towards side effect information needs to be further explored.

Footnotes

Declaration of conflicting interests

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The authors received no financial support for the research, authorship, and/or publication of this article.

ORCID iD

Mette Sieg

References

Beauchamp

. Informed consent: Its history, meaning, and present challenges. Camb Q Healthc Ethics 2011; 20: 515–523.

Siegler

. The progression of medicine: From physician paternalism to patient autonomy to bureaucratic parsimony. Arch Intern Med 1985; 145: 713–715.

Webster

Rubin

. Influencing side-effects to medicinal treatments: A systematic review of brief psychological interventions. Front Psychiatry 2019; 9: 1–15.

Evers

AWM

Colloca

Blease

, et al. Implications of placebo and nocebo effects for clinical practice: Expert consensus. Psychother Psychosom 2018; 87: 204–210.

Howick

Webster

Kirby

, et al. Rapid overview of systematic reviews of nocebo effects reported by patients taking placebos in clinical trials. Trials 2018; 19: 1–8.

Omonzejele

. Obligation of non-maleficence: Moral dilemma in physician–patient relationship. JMBR: A Peer-Rev J Biomed Sci 2005; 4: 22–30.

Cohen

. The nocebo effect of informed consent. Bioethics 2014; 28: 147–154.

Gelfand

. The nocebo effect and informed consent-taking autonomy seriously. Camb Q Healthc Ethics 2020; 29: 223–235.

. Commentary: Harm, truth, and the nocebo effect. Camb Q Healthc Ethics 2020; 29: 236–245.

10.

Cohen

. Preventing nocebo effects of informed consent without paternalism. Am J Bioeth 2017; 17: 44–46.

11.

Colloca

. Tell me the truth and I will not be harmed: Informed consents and nocebo effects. Am J Bioeth 2017; 17: 46–48.

12.

Fortunato

Wasserman

Menkes

. Nonmaleficence, nondisclosure, and nocebo: Response to open peer commentaries. Am J Bioeth 2017; 17: W4–W5.

13.

Fortunato

Wasserman

Menkes

. When respecting autonomy is harmful: A clinically useful approach to the nocebo effect. Am J Bioeth 2017; 17: 36–42.

14.

Nair

Dolovich

Cassels

, et al. What patients want to know about their medications. Focus group study of patient and clinician perspectives. Can Fam Physician 2002; 48: 104–110.

15.

Tarn

Wenger

Good

, et al.

Do physicians communicate the adverse effects of medications that older patients want to hear?

Drugs Ther Perspect 2015; 31: 68–76.

16.

Shin

Roter

Cho

, et al. Attitudes toward disclosure of medication side effects: A nationwide survey of Korean patients, caregivers, and oncologists. Psychooncology 2015; 24: 1398–1406.

17.

Berhane

Getahun

Azanaw

, et al. What patients want to know about their medication? A survey of inpatients and outpatients at Gondar University Hospital. Int J Pharm Sci Res 2013; 4: 434–439.

18.

Jenkins

Fallowfield

Saul

. Information needs of patients with cancer: Results from a large study in UK cancer centres. Br J Cancer 2001; 84: 48–51.

19.

Meredith

Symonds

Webster

, et al. Information needs of cancer patients in west Scotland: Cross sectional survey of patients’ views. Br Med J 1996; 313: 724–726.

20.

Chandrasenan

Morris

MWJ

Williams

. Patient’s views on consent for surgery: A questionnaire survey. Ann R Coll Surg Engl 2007; 89: 140–142.

21.

Degerliyurt

Gunsolley

Laskin

. Informed consent: What do patients really want to know? J Oral Maxillofac Surg 2010; 68: 1849–1852.

22.

Kastanias

Denny

Robinson

, et al.

What do adult surgical patients really want to know about pain and pain management?

Pain Manag Nurs 2009; 10: 22–31.

23.

Ziegler

Mosier

Buenaver

, et al.

How much information about adverse effects of medication do patients want from physicians?

Arch Intern Med 2001; 161: 706–713.

24.

Dawes

Davison

. Informed consent: What do patients want to know? J R Soc Med 1994; 87: 149–152.

25.

Beresford

Seymour

Vincent

, et al.

Risks of elective cardiac surgery: What do patients want to know?

Heart 2001; 86: 626–631.

26.

El-Wakeel

Taylor

Tate

JJT

. What do patients really want to know in an informed consent procedure? A questionnaire-based survey of patients in the bath area, UK. J Med Ethics 2006; 32: 612–616.

27.

Barnett

Charman

Sizer

, et al. Information given to patients about adverse effects of radiotherapy: A survey of patients’ views. Clin Oncol 2004; 16: 479–484.

28.

Kusch

MKP

Haefeli

Seidling

. Customization of information on adverse drug reactions according to patients’ needs – a qualitative study. Patient Educ Couns 2021; 104: 2351–2357.

29.

Keown

Slovic

Lichtenstein

. Attitudes of physicians, pharmacists, and laypersons toward seriousness and need for disclosure of prescription drug side effects. Health Psychol 1984; 3: 1–11.

30.

Krag

Nielsen

Norup

, et al.

Research report: Do general practitioners tell their patients about side effects to common treatments?

Soc Sci Med 2004; 59: 1677–1683.

31.

Nestoriuc

Pan

Kinitz

, et al. Informing about the nocebo effect affects patients’ need for information about antidepressants—an experimental online study. Front Psychiatry 2021; 12: 1–10.

32.

Büchter

Fechtelpeter

Knelangen

, et al. Words or numbers? Communicating risk of adverse effects in written consumer health information: A systematic review and meta-analysis. BMC Med Inform Decis Mak 2014; 14: 76.

33.

Moraes

da Silva Dal Pizzol

. Effect of different formats for information on side effects regarding medicine users’ understanding: A randomized controlled trial. Patient Educ Couns 2018; 101: 672–678.