Unblinded and Blinded N-of-1 Trials Versus Usual Care: A Randomized Controlled Trial to Increase Statin Uptake in Primary Care
Abstract
Background The aim was to assess whether an intervention incorporating a practicable open-label n-of-1 trial would lead to greater uptake of statin than usual care and comparable uptake to a closed-label gold-standard n-of-1 trial. Methods We enrolled patients who had stopped or declined statins into a 3-arm trial (usual care, unblinded, and blinded n-of-1 intervention arms). Physicians advised participants randomized to usual care to take statin therapy to prevent cardiovascular disease. In both intervention arms, physicians delivered a theoretically informed informed intervention endorsing the value of experimenting with medication in n-of-1 trials to assess whether it caused side-effects. In these trials, participants alternated between 4 weeks of medication and no medication (unblinded arm) or randomly sorted active and placebo (blinded arm) and recorded symptoms and symptom attributions for 6 months. Thereafter, physicians discussed participants' symptom reports during active/inactive treatment periods and asked participants to resume statins if appropriate. Results Seventy-three were randomized to the intervention arms and 20 to the control group. Fifty-six of 73 (77%) attempted the n-of-1 experiment; 28/36 (78%) in the unblinded arm; and 28/37 (76%) in the blinded arm. Forty-three of 56 (77%) completed the 6-month experiment and received feedback from the physician; 20/28 (71%) in the unblinded arm and 23/28 (82%) in the blinded arm. Thirty-three of 76 (45%) people res…
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In Tudor et al.'s n-of-1 statin rechallenge trial, which included a blinded and a non-blinded arm both receiving counselling from a primary care physician, there was little difference in symptoms between arms.
“Tudor et al. conducted a n-of-1 statin rechallenge trial that included a blinded and non-blinded arm, both receiving counselling from a primary care physician, and there was little difference in symptoms between arms [22].”
From Intolerance upon statin rechallenge: A systematic review and meta-analysis of randomized controlled trials (2023) · cites this paper as [22]
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N-of-1 Trial of a Statin, Placebo, or No Treatment to Assess Side Effects
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Warden, B. A., Guyton, J. R., Kovacs, A. C., Durham, J. A., Jones, L. K., Dixon, D. L., Jacobson, T. A., & Duell, P. B. (2023) · Journal of Clinical Lipidology · doi:10.1016/j.jacl.2022.09.001 · Cited by 111 · see citing works
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- Authors
- Tudor, K., Brooks, J., Howick, J., Fox, R., & Aveyard, P.
- Affiliations
- Warneford Hospital (GB)
- University of Oxford (GB)
- Bicester Health Centre, Coker Close, Bicester, United Kingdom (R.F.).
- Venue
- Circulation: Cardiovascular Quality and Outcomes
- Published
- 2022-06
- Volume
- 15
- Issue
- 6
- Pages
- e007793-e007793
- ISSN
- 1941-7705 (ISSN-L)
- 1941-7713
- OpenAlex
- W4282936831
- Cited by
- 9
- References
- 8
- Citations by year
- 2026: 4 · 2023: 2 · 2022: 3
- FWCI
- 1.19
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Circulation Cardiovascular Quality and Outcomes (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute for Health and Care Research (NIHR203808)
- Medical Research Council (MR/V020706/1)
- Topics
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Health Sciences › Medicine › Family Practice › Medication Adherence and Compliance
- Physical Sciences › Mathematics › Statistics and Probability › Statistical Methods in Clinical Trials
- Keywords
- N-of-1 trials, statin intolerance, medication adherence, physician feedback, cardiovascular disease prevention, primary care, symptom reporting, adverse events, patient decision-making, shared decision-making
- MeSH terms
- Humans, Primary Health Care, Hydroxymethylglutaryl-CoA Reductase Inhibitors
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