Tag: bias

The impact of leading questions on ME/CFS research: bias and stigma in study design

Abstract:

Background: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a complex and often misunderstood illness, characterized by post-exertional malaise, unrefreshing sleep, and cognitive impairments.

Objective: To investigate how question phrasing in ME/CFS research may influence participant attributions of fatigue/energy problems and unintentionally reinforce psychosomatic assumptions.

Methods: A total of 2248 individuals with ME/CFS from an international sample completed a survey assessing fatigue-related attributions. We analyzed how question wording influenced whether participants attributed their symptoms to physical or psychosocial causes. Particular focus was given to a fatigue attribution item that framed causes in terms of ‘personal life’ or ‘environmental factors.’

Results: Participants were significantly more likely to attribute their fatigue/energy problems to psychosocial factors when prompted with psychosocial framing. Many respondents who previously indicated physical causes as the primary source of their symptoms shifted to psychosocial explanations in response to the differently phrased item. This shift was especially pronounced among participants reporting higher levels of psychological distress.

Conclusions: Leading or biased question phrasing may distort participant responses in ME/CFS research, potentially inflating psychosomatic interpretations of the illness. Researchers should critically examine survey language to avoid introducing unintended bias that could compromise research validity and reinforce stigma.

Source: Campolattara, A. T. T., Jason, L. A., & Tuzzolino, K. C. (2025). The impact of leading questions on ME/CFS research: bias and stigma in study design. Fatigue: Biomedicine, Health & Behavior, 1–16. https://doi.org/10.1080/21641846.2025.2530338 https://www.tandfonline.com/doi/full/10.1080/21641846.2025.2530338

Response to treatment in the Multiple Symptoms Study 3 trial

Letter:
Chistopher Burton and colleagues conducted an unblinded trial of a consultative intervention for 354 people with persistent physical symptoms but no identifiable “organic” cause. Patient Health Questionnaire-15 (PHQ-15) score, which is a brief, subjective, self-administered screen of severity of somatic complaints, was the primary outcome. This kind of trial design can be expected to produce modest positive outcomes, via expectation bias alone. No real-life, objective assessment of functioning was conducted.
The intervention involved up to four sessions with a general practitioner, offering patients “rational explanations” for their symptoms in the absence of known, falsifiable causes and helping patients to develop strategies for managing symptoms. Although the “rational explanations” are not described, they presumably did not include “organic” diseases or conditions.
Scores on the PHQ-15 range from 0 to 30. Recruited patients had scores from 10 to 20, indicating moderate severity. At the end of the study, the adjusted between-group difference of –1·82 did not reach the minimal clinically important difference of 2·3. The change is well within what would be expected from bias alone. The results therefore confirmed that the intervention was of limited, if any, practical benefit. However, the paper presents the findings as though they had shown the opposite.
Instead of the “rational explanations” promoted by the investigators, more straightforward and honest explanations—for example, we do not know what is causing symptoms—could easily have produced similar results. Patients desire resolution of symptoms and recovery of functions. The trial did not achieve this result. Post-intervention, participants continue to have an impaired quality of life and poor experiences of health care.
DT holds an academic position at the Center for Global Public Health at UC Berkeley, which is largely supported by crowdfunded donations directly to the university, many of them from patients with myalgic encephalomyelitis or chronic fatigue syndrome and related conditions that fall under the heading of persistent physical symptoms. JSC declares no competing interests.
Source: Joan S Crawford and David Tuller. Response to treatment in the Multiple Symptoms Study 3 trial.  The Lancet, Volume 405, Issue 10485, 1145 – 1146  https://link.springer.com/article/10.1007/s00421-025-05759-5 (Full text)

Bias in Exercise Trials for ME/CFS: the Importance of Objective Outcomes and Long-term Follow-up

Sharpe and colleagues recommend that patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) be offered cognitive behavior therapy (CBT) and graded exercise therapy (GET)1, advice that contrasts with recent NICE guidance on ME/CFS.2 The authors argue that “there are many randomized trials indicating the safety and efficacy of these treatments.”1

All of these trials, however, were nonblinded and relied on subjective symptom questionnaires as their main outcomes, a combination that creates a high risk of response bias. Treatment manuals used in these trials included explicit encouragements to raise patients’ expectations of GET and CBT. One patient booklet, for example, informed patients: “You will experience a snowballing effect as increasing fitness leads to increasing confidence in your ability. You will have conquered CFS by your own effort and you will be back in control of your body again.”3 These encouragements were not provided to participants in the control group and might have influenced how patients rated their health. In contrast to what Sharpe and colleagues claim, measuring the expectations of patients before the trial begins, does not address how therapists might have influenced symptom reporting during the trial.

There are further arguments that suggest these trials might have measured response bias rather than improvements in health. There were, for example, no clinically significant differences on objective outcome measures that are less prone to response bias such as employment figures, activity levels, or fitness tests.3 In addition, at long-term follow-up, the control group seemed to perform just as well as participants who received GET or CBT. This could not be explained by additional treatment received after the trial ended.4 These findings are difficult to interpret if patients did indeed rehabilitate successfully following GET or CBT. It is unfortunate that the authors, who were primary researchers in many of these trials, do not address these concerns.

Lastly, Sharpe and colleagues argue that “harm reported from patient community surveys reflects poorly implemented therapy.”1 Patient surveys, however, indicate that ME/CFS patients report harm of GET even if prescribed by a specialist or physiotherapist.5 The authors have previously been challenged for misrepresenting the findings of these surveys.5 Post-exertional malaise or a marked worsening of symptoms when patients exceed their energy limit, is a characteristic feature of ME/CFS.2 There are therefore reasonable safety concerns about treatments such as GET and CBT that try to push patients to exceed their limits.

Read the full article HERE.

Source: Tack, M. Bias in Exercise Trials for ME/CFS: the Importance of Objective Outcomes and Long-term Follow-up. J GEN INTERN MED 37, 3193 (2022). https://doi.org/10.1007/s11606-022-07704-0  (Full text)

Toward Unbiased Evaluation of Postacute Sequelae of SARS-CoV-2 Infection: Challenges and Solutions for the Long Haul Ahead

Abstract:

The authors argue that postacute SARS-CoV-2 syndrome presents unique challenges in determining risk factors, natural history, and proper management. They call for strategies and actions that are based on rigorous, high-quality evidence.

Source: Wisk LE, Nichol G, Elmore JG. Toward Unbiased Evaluation of Postacute Sequelae of SARS-CoV-2 Infection: Challenges and Solutions for the Long Haul Ahead. Ann Intern Med. 2022 Mar 8:M21-4664. doi: 10.7326/M21-4664. Epub ahead of print. PMID: 35254883; PMCID: PMC8906529. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8906529/ (Full text)

Graded Exercise Therapy Doesn’t Restore the Ability to Work in ME/CFS. Rethinking of a Cochrane Review

Abstract:

Background: Cochrane recently amended its exercise review for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) in response to an official complaint.

Objective: To determine if the amended review has addressed the concerns raised about the previous review and if exercise is an effective treatment that restores the ability to work in ME/CFS.

Method: The authors reviewed the amended Cochrane exercise review and the eight trials in it by paying particular interest to the objective outcomes. We also summarised the recently published review of work rehabilitation and medical retirement for ME/CFS.

Results: The Cochrane review concluded that graded exercise therapy (GET) improves fatigue at the end of treatment compared to no-treatment. However, the review did not consider the unreliability of subjective outcomes in non-blinded trials, the objective outcomes which showed that GET is not effective, or the serious flaws of the studies included in the review. These flaws included badly matched control groups, relying on an unreliable fatigue instrument as primary outcome, outcome switching, p-hacking, ignoring evidence of harms, etc. The review did also not take into account that GET does not restore the ability to work.

Conclusion: GET not only fails to objectively improve function significantly or to restore the ability to work, but it’s also detrimental to the health of≥50% of patients, according to a multitude of patient surveys. Consequently, it should not be recommended.

Source: Vink M, Vink-Niese F. Graded exercise therapy doesn’t restore the ability to work in ME/CFS. Rethinking of a Cochrane review [published online ahead of print, 2020 Jun 14]. Work. 2020;10.3233/WOR-203174. doi:10.3233/WOR-203174 https://pubmed.ncbi.nlm.nih.gov/32568149/

The problem of bias in behavioural intervention studies: Lessons from the PACE trial

Abstract:

Geraghty’s recent editorial on the PACE trial for chronic fatigue syndrome has stimulated a lively discussion. Here, I consider whether the published claims are justified by the data. I also discuss wider issues concerning trial procedures, researcher allegiance and participant reporting bias. Cognitive behavioural therapy and graded exercise therapy had modest, time-limited effects on self-report measures, but little effect on more objective measures such as fitness and employment status. Given that the trial was non-blinded, and the favoured treatments were promoted to participants as ‘highly effective’, these effects may reflect participant response bias. In non-blinded trials, the issue of reporting biases deserves greater attention in future.

 

Source: Carolyn Wilshire. The problem of bias in behavioural intervention studies: Lessons from the PACE trial. Journal of Health Psychology. First published date: March-23-2017. http://journals.sagepub.com/doi/full/10.1177/1359105317700885 (Full article)

 

Reviewing the reviews: the example of chronic fatigue syndrome

Abstract:

OBJECTIVE: To test the hypothesis that the selection of literature in review articles is unsystematic and is influenced by the authors’ discipline and country of residence.

DATA SOURCES: Reviews in English published between 1980 and March 1996 in MEDLINE, EMBASE (BIDS), PSYCHLIT, and Current Contents were searched.

STUDY SELECTION: Reviews of chronic fatigue syndrome (CFS) were selected. Articles explicitly concerned with a specialty aspect of CFS and unattributed, unreferenced, or insufficiently referenced articles were discarded.

DATA EXTRACTION: Record of data sources in each review was noted as was the departmental specialty of the first author and his or her country of residence. The references cited in each index paper were tabulated by assigning them to 6 specialty categories, by article title, and by assigning them to 8 categories, by country of journal publication.

DATA SYNTHESIS: Of 89 reviews, 3 (3.4%) reported on literature search and described search method. Authors from laboratory-based disciplines preferentially cited laboratory references, while psychiatry-based disciplines preferentially cited psychiatric literature (P = .01). A total of 71.6% of references cited by US authors were from US journals, while 54.9% of references cited by United Kingdom authors were published in United Kingdom journals (P = .001).

CONCLUSION: Citation of the literature is influenced by review authors’ discipline and nationality.

 

Source: Joyce J, Rabe-Hesketh S, Wessely S. Reviewing the reviews: the example of chronic fatigue syndrome. JAMA. 1998 Jul 15;280(3):264-6. http://www.ncbi.nlm.nih.gov/pubmed/9676676

 

Post-viral fatigue syndrome. Epidemiology: lessons from the past

Abstract:

This chapter outlines the recorded epidemiological history of PVFS (including the early epidemics of myalgic encephalomyelitis) and the development of the concept, including the realisation that endemic cases also occur.

Cases of PVFS are still not recorded by the Surveillance Centre for Communicable Diseases, so it is very difficult to detect and monitor any outbreak in the community, since each GP may only have two or three such patients and would, therefore, not be aware of an epidemic in the community as a whole if it occurred.

Epidemiological issues raised by the early epidemics, including the delineation of the syndrome, the question of bias, the role of hysteria and the role of depression; the issue of symptom distribution, and its implications for aetiology; and a multiaxial framework for understanding the association with psychological symptoms are discussed. The value of a future multidisciplinary research programme designed to disentangle direct and predisposing causes of PVFS is emphasised.

 

Source: Jenkins R. Post-viral fatigue syndrome. Epidemiology: lessons from the past. Br Med Bull. 1991 Oct;47(4):952-65. http://www.ncbi.nlm.nih.gov/pubmed/1794093