Background: Clinical medicine and healthcare policy are increasingly guided by randomized controlled trials, which in turn are dependent on the validity of placebo control. It is important to understand the effects of placebo control on outcome measurement, especially for assessment of symptoms and functional impairments where subjectivity, expectancy, and motivation may significantly impact outcome evaluation. This paper describes the rationale and methodology of a trial designed to evaluate placebo effects related to taking pills and to compare these with effects attributable to standard or enhanced (patient-oriented) doctor-patient interaction.
Design: This trial uses two-way factorial allocation to randomize people with new onset common cold in two directions: pill related and doctor related. In one direction, participants are randomized to (1) no pills, (2) blinded placebo, (3) blinded echinacea, or (4) unblinded open-label echinacea. In the other direction, participants are randomized to: (1) no doctor-patient interaction, (2) standard doctor-patient interaction, and (3) enhanced doctor-patient interaction. Enhanced interaction includes education, empathy, empowerment, positive prognosis, and connectedness. Area under the time severity curve is the primary outcome, with the Wisconsin Upper Respiratory Symptom Survey (WURSS-21) the measure of severity. A priori power studies called for a sample size of N = 720 trial finishers to detect 15% to 20% between-group differences in this outcome. Secondary outcomes include general health-related quality of life, perceived stress, interpersonal support, optimism, patient satisfaction, and positive and negative affectivity. Two biomarkers are also assessed: interleukin-8 (inflammatory cytokine) and neutrophil count from nasal wash.
Importance: This paper describes the rationale and methodology of a trial assessing placebo effects related to pills and to doctor-patient interaction. This is one of very few similar studies and is the first in the common cold. Data collected will also provide an excellent opportunity to investigate relationships among demographic (age, sex, education, income) and psychosocial (perceived stress, interpersonal support, optimism, affectivity) indicators in relation to common cold outcomes.