The Effect of Methylphenidate on Fatigue in Advanced Cancer: An Aggregated N-of-1 Trial

Mitchell, G.; Hardy, Janet; Nikles, Jane; Carmont, Sue-Ann; Senior, Hugh; Schluter, Philip J.; Good, Phillip; Currow, David C.

doi:10.1016/j.jpainsymman.2015.03.009

Cited by 44 publications

(53 citation statements)

References 28 publications

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“…N-of-1 trials have been used to assess therapeutic options in the most vulnerable populations. To assess the effectiveness of a psychostimulant (methylphenidate) on fatigue in patients with advanced cancer, a group of researchers used N-of-1 trial methodology to halve the sample size required to estimate population effects [47]. Forty-three patients were enrolled with 24 completing three random cycles (active and placebo periods).…”

Section: Patient-centred Approachmentioning

confidence: 99%

Practice-Based Research in Complementary Medicine: Could N-of-1 Trials Become the New Gold Standard?

2020

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Complementary medicines and therapies are popular forms of healthcare with a long history of traditional use. Yet, despite increasing consumer demand, there is an ongoing exclusion of complementary medicines from mainstream healthcare systems. A lack of evidence is often cited as justification. Until recently, high-quality evidence of treatment efficacy was defined as findings from well-conducted systematic reviews and meta-analyses of randomized controlled trials. In a recent and welcome move by the Oxford Centre for Evidence-Based Practice, however, the N-of-1 trial design has also been elevated to the highest level of evidence for treatment efficacy of an individual, placing this research design on par with the meta-analysis. N-of-1 trial designs are experimental research methods that can be implemented in clinical practice. They incorporate much of the rigor of group clinical trials, but are designed for individual patients. Individualizing treatment interventions and outcomes in research designs is consistent with the movement towards patient-centered care and aligns well with the principles of holism as practiced by naturopaths and many other complementary medicine practitioners. This paper explores whether rigorously designed and conducted N-of-1 trials could become a new ‘gold standard’ for demonstrating treatment efficacy for complementary medicine interventions in individual patients in clinical practice.

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Section: Patient-centred Approachmentioning

confidence: 99%

Practice-Based Research in Complementary Medicine: Could N-of-1 Trials Become the New Gold Standard?

2020

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“…Fourteen randomized clinical trials have been published [23][24][25][26][27][28][29][30][31][32][33][34][35][36]: nine with methylphenidate, one with dexamphetamine, two with modafinil and two with armodafinil (Table 1). All these drugs had small pilot studies suggesting possible benefits in control of CRF.…”

Section: Pharmacological Treatmentmentioning

confidence: 99%

Management of Fatigue Following Breast Cancer Treatment

Roila

Fumi

Fatigoni

2016

Breast Cancer Manag.

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Cancer-related fatigue (CRF) is a very distressing symptom experienced by most cancer patients. CRF is a complex symptom and there is no agreement regarding the exact definition, the best measurement instrument or even the optimal treatment. CRF is an important problem especially in breast cancer patients, during and after treatment, in long-term survivors. In the last few decades survival rates have dramatically improved. Thus, the number of breast cancer survivors has increased and preservation of quality of life has become very important. This paper is a literature review of the studies published in the last 5 years on management of CRF and breast cancer patients. We distinguished CRF during and after oncological therapy and examined both pharmacological and nonpharmacological interventions.

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“…When these conditions apply, N-of-1 trials provide the highest form of evidence for individual patients [17, 18]. When the same N-of-1 trial protocol is used for several individuals, aggregated data can be used to estimate the treatment effect at population level, as robustly as with traditional parallel-armed RCTs [19]. 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].…”

Section: Introductionmentioning

confidence: 99%

“…When the same N-of-1 trial protocol is used for several individuals, aggregated data can be used to estimate the treatment effect at population level, as robustly as with traditional parallel-armed RCTs [19]. 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].…”

Section: Introductionmentioning

confidence: 99%

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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The Effect of Methylphenidate on Fatigue in Advanced Cancer: An Aggregated N-of-1 Trial

Cited by 44 publications

References 28 publications

Practice-Based Research in Complementary Medicine: Could N-of-1 Trials Become the New Gold Standard?

Practice-Based Research in Complementary Medicine: Could N-of-1 Trials Become the New Gold Standard?

Management of Fatigue Following Breast Cancer Treatment

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

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