A Time-to-Deterioration (TTD) N-of-1 Clinical Trial Design for Use in Homeopathy Research
05 February 2020 (online)
Background: Application of the randomised controlled trial (RCT) in research into individualized homeopathy has several known limitations, such as selecting the appropriate individual remedy, and inherent ethical problems of placebo interventions.
Methods: Based on recent considerations of the possible use of N-of-1 trials in homeopathy and its limitations, we developed a modification of the N-of-1 trial design.
Results: The key element of the proposed study design is to select ‘time to deterioration’ (TTD) after intervention as primary outcome in an N-of-1 trial. We assume a positive homeopathic treatment effect relative to baseline on a given measurement scale (e.g. Conners Global Index (CGI) in ADHD). If treatment consists e.g. of a few doses of Q-potencies, deterioration can be expected after some time. After reaching a particular threshold value (TV) in the outcome scale (e.g. 30% decrease of CGI), the next trial medication is given. Verum and placebo are administered double-blind and randomly in time. Assuming that verum has stronger effects than placebo, the timespan until TV is reached is longer after verum application compared to placebo. The adequate homeopathic remedy can be determined in an open or single-blind screening phase with an adequate success criterion (e.g. 50% improvement in CGI). Data from TTD N-of-1 trials can be easily aggregated and synthesized in meta-analysis, since the outcome is always measured in time units.
Discussion: The TTD trial design is appropriate for chronic stable conditions. Major advantages are: placebo phases are self-limiting and as short as possible, thus minimising ethical problems and patient drop-out; carry-over effects are limited by the choice of the threshold value; TTD data yield information on duration and time-course of homeopathic as well as placebo treatments. Placebo could be replaced by another homeopathic remedy to compare efficacy of different treatment options.
Keywords: N-of-1 trial, research methodology, homeopathy