Geoffrey K Mitchell1, Janet R Hardy2, Catherine J Nikles3, Sue-Ann S Carmont3, Hugh E Senior3, Philip J Schluter4, Phillip Good5, David C Currow6. 1. School of Medicine, University of Queensland, Brisbane, Queensland, Australia. Electronic address: g.mitchell@uq.edu.au. 2. Department of Palliative and Supportive Care, Mater Health Services, South Brisbane, Queensland, Australia; Mater Research, University of Queensland, South Brisbane, Queensland, Australia. 3. School of Medicine, University of Queensland, Brisbane, Queensland, Australia. 4. School of Health Sciences, University of Canterbury, Christchurch, New Zealand. 5. Department of Palliative and Supportive Care, Mater Health Services, South Brisbane, Queensland, Australia; Mater Research, University of Queensland, South Brisbane, Queensland, Australia; St. Vincent's Private Hospital, Brisbane, Queensland, Australia. 6. Cancer Institute of New South Wales, Sydney, New South Wales, Australia; Department of Palliative and Supportive Care, Flinders University, Adelaide, South Australia, Australia.
Abstract
CONTEXT: Fatigue is common in life-limiting cancer. Methylphenidate (MPH), a psychostimulant, may be a useful therapy. Gathering evidence in patients with advanced cancer can be challenging. OBJECTIVES: To determine if MPH improves cancer-related fatigue in people with advanced cancer. METHODS: N-of-1 trials are multicycle, double-blind, randomized, controlled crossover trials using standardized measures of effect in individuals. They are normally used to assess treatment effects in individuals. Aggregated N-of-1 trials from participants with end-stage cancer suffering fatigue were used to assess the group effect of MPH, producing an estimate of equivalent power to a parallel-group randomized controlled trial (RCT) but requiring less than half of the sample size. Up to three cycles of MPH 5 mg twice daily (three days) vs. identical placebo (three days) capsules were offered to participants. Primary outcome was improvement in fatigue as measured by the Functional Assessment of Chronic Illness Therapy-Fatigue Scale and the Wu Cancer Fatigue Scale. Analysis used Bayesian statistical methods using intention-to-treat principles. RESULTS: Forty-three participants completed 84 cycles of MPH and placebo in random order, exceeding sample size estimates. Overall, MPH did not improve fatigue (mean difference 3.2; 95% credible interval -2.0, 9.0; posterior probability of favorable effect 0.890). Eight participants showed important improvement, and one participant showed important worsening of fatigue on MPH. There were no features that distinguished participants whose fatigue responded to MPH compared with those who did not. CONCLUSION:MPH does not improve fatigue in the population of patients with end-stage cancer. Aggregated N-of-1 trial methodology is feasible and produces population-based sample estimates with less than half the sample size required for the equivalent parallel-group RCT. It also identified individuals who did and did not respond to MPH, which is a feature difficult to achieve in a standard RCT. The study was registered with the Australian Clinical Trials Registry (12609000794202). Crown
RCT Entities:
CONTEXT: Fatigue is common in life-limiting cancer. Methylphenidate (MPH), a psychostimulant, may be a useful therapy. Gathering evidence in patients with advanced cancer can be challenging. OBJECTIVES: To determine if MPH improves cancer-related fatigue in people with advanced cancer. METHODS: N-of-1 trials are multicycle, double-blind, randomized, controlled crossover trials using standardized measures of effect in individuals. They are normally used to assess treatment effects in individuals. Aggregated N-of-1 trials from participants with end-stage cancer suffering fatigue were used to assess the group effect of MPH, producing an estimate of equivalent power to a parallel-group randomized controlled trial (RCT) but requiring less than half of the sample size. Up to three cycles of MPH 5 mg twice daily (three days) vs. identical placebo (three days) capsules were offered to participants. Primary outcome was improvement in fatigue as measured by the Functional Assessment of Chronic Illness Therapy-Fatigue Scale and the Wu CancerFatigue Scale. Analysis used Bayesian statistical methods using intention-to-treat principles. RESULTS: Forty-three participants completed 84 cycles of MPH and placebo in random order, exceeding sample size estimates. Overall, MPH did not improve fatigue (mean difference 3.2; 95% credible interval -2.0, 9.0; posterior probability of favorable effect 0.890). Eight participants showed important improvement, and one participant showed important worsening of fatigue on MPH. There were no features that distinguished participants whose fatigue responded to MPH compared with those who did not. CONCLUSION:MPH does not improve fatigue in the population of patients with end-stage cancer. Aggregated N-of-1 trial methodology is feasible and produces population-based sample estimates with less than half the sample size required for the equivalent parallel-group RCT. It also identified individuals who did and did not respond to MPH, which is a feature difficult to achieve in a standard RCT. The study was registered with the Australian Clinical Trials Registry (12609000794202). Crown
Authors: Bas C Stunnenberg; Joost Raaphorst; Hans M Groenewoud; Jeffrey M Statland; Robert C Griggs; Willem Woertman; Dick F Stegeman; Janneke Timmermans; Jaya Trivedi; Emma Matthews; Christiaan G J Saris; Bas J Schouwenberg; Gea Drost; Baziel G M van Engelen; Gert Jan van der Wilt Journal: JAMA Date: 2018-12-11 Impact factor: 56.272
Authors: Stephanie S Weinreich; Charlotte Vrinten; Marja R Kuijpers; Alexander F Lipka; Kirsten J M Schimmel; Erik W van Zwet; Christine Gispen-de Wied; Yechiel A Hekster; Jan J G M Verschuuren; Martina C Cornel Journal: Orphanet J Rare Dis Date: 2017-05-12 Impact factor: 4.123
Authors: J Nikles; J D O'Sullivan; G K Mitchell; S S Smith; J M McGree; H Senior; N Dissanyaka; A Ritchie Journal: Contemp Clin Trials Commun Date: 2019-07-08
Authors: J Nikles; R L Tate; G Mitchell; M Perdices; J M McGree; C Freeman; S Jacob; M W Taing; M Sterling Journal: Contemp Clin Trials Commun Date: 2019-10-28
Authors: Annelieke R Müller; Marion M M G Brands; Peter M van de Ven; Kit C B Roes; Martina C Cornel; Clara D M van Karnebeek; Frits A Wijburg; Joost G Daams; Erik Boot; Agnies M van Eeghen Journal: Neurology Date: 2021-01-27 Impact factor: 9.910