Stakeholders' views on the routine use of n-of-1 trials to improve clinical care and to make resource allocation decisions for drug use

Nikles, Jane; Mitchell, G.; Clavarino, Alexandra; Yelland, Michael; Mar, Chris Del

doi:10.1071/ah09654

Cited by 10 publications

(15 citation statements)

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“…Nikles et al studied the feasibility and usefulness of N-of-1 trials from multiple perspectives, by interviewing representatives of various Australian stakeholder groups including health care, clinician and patient organisations [21]. The interviewees had varying degrees of familiarity with N-of-1 trials, in contrast to our study which studied responses to a concrete trial.…”

Section: Discussionmentioning

confidence: 96%

“…Although in the Nikles study stakeholders mentioned utility of N-of-1 trials in conjunction with reimbursement, this always seemed to be in the context of expensive drugs or drugs with contested cost-effectiveness. Possibly, N-of-1 trials are not needed in Australia for inexpensive unlicensed treatments for rare diseases, if treatments of that type are more accessible than in the Netherlands [21]. …”

Section: Discussionmentioning

confidence: 99%

“…The interviews were semi-structured, based on an interview guide with questions and prompts. The topics were based on theoretical benefits and burdens of N-of-1 trials [16], published studies on patients ‘and carers’ experiences with N-of-1 trials [21, 32], and process-related aspects of the trial at hand. The interviews were held by telephone, audio recorded (after verbal affirmation of consent) and lasted up to 30 min.…”

Section: Methodsmentioning

confidence: 99%

“…Moreover, because each patient provides several sets of matched data to each trial “arm”, generally smaller sample sizes are needed than in conventional RCTs [16, 19, 20]. However, compared to equally powered trial designs addressing the same clinical question, N-of-1 trials may be more burdensome for patients if the trial lasts longer (due to multiple cross-overs) and requires intensive data collection (e.g., diaries, outpatient visits) [16, 21]. A systematic review illustrates that N-of-1 trials have been published for many indications [22], but there are almost no published examples that evidence from N-of-1 trials was used for a decision for licensing or reimbursement of a treatment for a small patient group.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Aggregated N-of-1 trials for unlicensed medicines for small populations: an assessment of a trial with ephedrine for myasthenia gravis

Weinreich

Vrinten

Kuijpers

et al. 2017

Orphanet J Rare Dis

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BackgroundInexpensive medicines with a long history of use may currently be prescribed off-label for rare indications. Reimbursement is at the discretion of health insurance companies, and may be unpredictable. The example addressed was ephedrine as add-on treatment for myasthenia gravis. Stakeholders from academia, a patient organization, the Dutch National Health Care Institute (NHCI) and Dutch Medicines Evaluation Board (MEB) advised on the trial design. The NHCI and MEB agreed to provide scientific advice on the suitability of the evidence generated by the trial, for regulatory decisions. This paper describes the feasibility of the trial and the utility of its aggregated results.ResultsThe trialists experienced the trial as feasible. Retrospective interviews showed that the trial as performed was acceptable to patients. The treatment effect in the primary outcome measure, muscle strength, was statistically significant when inferred to the population level, though the effect size was modest. Secondary outcomes were statistically significant in a preplanned, fixed effects analysis within the four patients. The NHCI advised that it could potentially make reimbursement decisions based on the Fitting Evidence framework, should the trialists decide to apply for reimbursement. The MEB advised that for a licensing decision, the N-of-1 design is a last-resort option for demonstrating treatment benefit in a rare disease. N-of-1 trials alone do not provide enough evidence on potential risk. The MEB found the current trial inconclusive. It suggested doing a 2-armed trial of longer duration, possibly with a different outcome measure (postponement of corticosteroid use). It suggested engaging a consultancy or commercial sponsor, should the trialists decide to seek market authorization of the drug.ConclusionsIn theory, evidence from aggregated N-of-1 trials is suitable for use in licensing and reimbursement decisions. The current example illustrates differences in interpretation of N-of-1 results by health authorities. In the era of personalized medicine, consensus is required on the interpretation of data from study designs geared to small groups. Demonstrating effectiveness of inexpensive medicines in small populations may require involvement of non-commercial parties, to preserve affordability.Electronic supplementary materialThe online version of this article (doi:10.1186/s13023-017-0636-y) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Aggregated N-of-1 trials for unlicensed medicines for small populations: an assessment of a trial with ephedrine for myasthenia gravis

Weinreich

Vrinten

Kuijpers

et al. 2017

Orphanet J Rare Dis

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“…Several recent pilot studies (Brookes et al 2007, Kravitz et al 2009, Nikles et al 2010) examined the acceptability for the SPT among potential end users (patients and clinicians, and other stakeholders). The results are generally encouraging for this personalized approach for clinical decisionmaking.…”

Section: Single-patient Trials (Spts): a "Small Data" Methodologymentioning

confidence: 99%

Big Data and Small Data: Reflections on data science, statistical modeling, and financial and health care reforms

Duan

2014

Notices of the International Congress of Chinese Mathematicians

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Comparing pregabalin and gabapentin for persistent neuropathic pain: A protocol for a pilot N-of-1 trial series

Bashford

Tan

McGree

et al. 2021

Contemporary Clinical Trials Communications

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Background Evidence-based management of neuropathic pain is commonly ineffective due to the large variability in response between cases. Patients often have to trial several drugs before finding one that provides adequate relief, leading to increased costs and worsened outcomes. There is thus a need for tools to guide and streamline prescribing decisions in neuropathic pain. N-of-1 trials provide a potentially precise and economical method of selecting between multiple interventions in an individual patient, and merit a feasibility assessment for use in clinical pain practice. Aims We aim to evaluate the feasibility of N-of-1 trials to compare pregabalin and gabapentin for individual presentations of neuropathic pain. Methods This is a double-blinded multiple crossover study, with recruitment from existing patients at an outpatient pain clinic in New South Wales, Australia. Participants will undergo three 4-week treatment pairs, comprising 2 weeks of pregabalin (150–600 mg/day) and 2 weeks of gabapentin (900–3600 mg/day), in an individually randomised order. Intervention doses will be derived from participants’ existing treatment dose. Medications will be taken orally three times daily. The primary outcome will be pain intensity; measures will be self-reported daily in patient diaries. After completing all three cycles, participants and their physicians will be presented with the results of the trial to form an informed decision about their treatment. Discussion As a stable yet debilitating condition, neuropathic pain is especially amenable to an N-of-1 study design. A successful trial would represent a significant quality of life improvement for the patient, possibly extending over the course of their lifetime.

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Stakeholders' views on the routine use of n-of-1 trials to improve clinical care and to make resource allocation decisions for drug use

Abstract: Background: N-of-1 trials are empirical formal tests using a within-patient randomised, double-

Cited by 10 publications

References 14 publications

Aggregated N-of-1 trials for unlicensed medicines for small populations: an assessment of a trial with ephedrine for myasthenia gravis

Aggregated N-of-1 trials for unlicensed medicines for small populations: an assessment of a trial with ephedrine for myasthenia gravis

Big Data and Small Data: Reflections on data science, statistical modeling, and financial and health care reforms

Comparing pregabalin and gabapentin for persistent neuropathic pain: A protocol for a pilot N-of-1 trial series

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