Determining Optimal Therapy — Randomized Trials in Individual Patients

Abstract

Although the treatment of an individual patient in routine clinical practice has been likened to an experiment, the method is so susceptible to bias that we have come to demand multi-patient, double-blind, randomized controlled trials on matters of efficacy. Unfortunately, such trials have not or cannot be carried out for many clinical disorders; even when they have been executed their results may be difficult to extrapolate to individual patients. To resolve this problem, we have begun to use double-blind randomized trials in which a single patient undergoes a series of pairs of treatments, consisting of one active and one placebo or alternative treatment per pair, with the order determined by random allocation. Appropriate treatment targets (signs, symptoms, or laboratory tests) are used as the measure of efficacy, and the trial is continued until efficacy is established or disproved. We describe such a trial, which resulted in a dramatically beneficial modification of treatment in a patient with partially reversible airflow limitation. We have established a clinical service that facilitates the widespread use of the method in our community.

Challenges in the Design and Conduct of Therapeutic Trials in Channel Disorders

“…5 An n-of-1 clinical trial uses randomization, blinding, and reliable endpoints, but the outcome (beneficial or not) is specific to that individual. 11 In other words, an n-of-1 trial is an RCT for one individual. The study treatment-intervention and placebo-comparator are administered in a randomized order with the outcome(s) assessed in a blinded manner.…”

“…The trial will consist of repeated paired treatment cycles (each cycle a separate randomization of the allocation order for intervention and placebo) until it becomes evident whether the intervention is or is not effective. 11,12 Multiple n-of-1 clinical trials may be combined to estimate population effects, similar to a crossover trial. 12 While these alternatives to parallel group RCT are attractive, careful trial design remains necessary as potential pitfalls exist for conducting therapeutic trials in neurological channelopathies.…”

Diretrizes metodológicas para investigar estados alterados de consciência e experiências anômalas

“…Urge reconhecer os diversos viéses a que estão sujeitos os achados de nossa experiência clínica. Entre eles, temos o efeito placebo, o retorno à média, a evolução natural da doença e a tendenciosidade do paciente e do examinador na avaliação dos resultados (Guyatt et al, 1986;Sackett, 1985). Além desses, há o fato de que muitos pacientes que não se julgam melhorados com a abordagem recebida simplesmente mudam de profissional, havendo uma tendência a recebermos o retorno daqueles que tiveram melhor evolução.…”

Individualization of antihypertensive therapy.

“…6 Improvements in the evaluation of blood pressure changes used together with appropriate designs for sequential drug administration will allow for a more precise analysis of the efficacy of drugs in a given patient, thus offering a clinically based approach for optimization of individual therapy. 7 Group analysis of the antihypertensive effect of two antihypertensive treatments conceals behind its global result a variable proportion of individual good responders, nonresponders, and possibly even some patients who experienced a pressure increase. 8 Even if the average effect of Drug A is less pronounced than that of Drug B, Drug B may still be more efficacious in some individuals than Drug A.…”