The Effect of Methylphenidate on Fatigue in Advanced Cancer: An Aggregated N-of-1
Trial.
Author(s): Mitchell GK(1), Hardy JR(2), Nikles CJ(3), Carmont SA(3), Senior HE(3), Schluter
PJ(4), Good P(5), Currow DC(6).
Affiliation(s): Author information:
(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.
Publication date & source: 2015, J Pain Symptom Manage. ,
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).
|