Making smart investment decisions in clinical research

Abstract A recent trial in rheumatoid arthritis found an inexpensive, but infrequently used, combination of therapies is neither inferior nor less safe than an expensive biologic drug. If the trial had been conducted over 10 years ago, arguably 100’s of millions of dollars since spent on biologics could have been released to other, more effective treatments. Given the ever increasing number of trials proposed, this commentary uses the trial as an example to challenge payers and research funders to make smarter investments in clinical research to save potential future costs. Trial registration: NCT00405275 , registered 29 November 200

Rheumatoid arthritis triple therapy compared with etanercept: difference in infectious and gastrointestinal adverse events

Objective.: The main aim of this study was to examine the differences between triple therapy (T: SSZ and HCQ added to MTX) and etanercept (E) added to MTX with regard to the infectious and gastrointestinal (GI) adverse events (AEs) reported in The Rheumatoid Arthritis Comparison of Active Therapies Trial. Methods.: The patients were 353 RA MTX incomplete responders who were randomized to T (n = 178) or E (n = 175). Of these, 88 patients were switched to the alternative treatment from the initial treatment (E or T) at 24 weeks per protocol. Infectious and GI serious AEs (SAEs) and non-serious AEs (NAEs) were reported during 48 and 4 weeks after the intervention period. Generalized linear models were used to estimate the incidence rate ratios (IRRs) of AEs between the two therapies. Results.: Patients on E therapy were more likely to have infectious NAEs (IRR = 1.56, 95% CI: 1.11, 2.19). There was a greater number of infectious SAEs that occurred when patients received E than T therapy [12 E (6.9%) vs 4 T (2.2%), P = 0.19]. Pneumonia was the most common infectious SAE for both treatments [6 E (3.4%) and 2 T (1.1%)]. Conversely, patients who were on E were less likely to have GI NAEs than those on T therapy (IRR = 0.62, 95% CI: 0.40, 0.94). The most common GI SAE reported was GI haemorrhage, which occurred among three patients on E (1.7%). Conclusion.: This study provides evidence of different likelihoods of infectious and GI AEs associated with two common, equally effective treatments for RA patients who have had incomplete responses to MTX

Making smart investment decisions in clinical research

A recent trial in rheumatoid arthritis found an inexpensive, but infrequently used, combination of therapies is neither inferior nor less safe than an expensive biologic drug. If the trial had been conducted over 10 years ago, arguably 100’s of millions of dollars since spent on biologics could have been released to other, more effective treatments. Given the ever increasing number of trials proposed, this commentary uses the trial as an example to challenge payers and research funders to make smarter investments in clinical research to save potential future costs. Trial registration: NCT00405275 , registered 29 November 2006Medicine, Faculty ofOther UBCNon UBCPopulation and Public Health (SPPH), School ofReviewedFacult

Design and conduct of a provider survey to determine a clinically persuasive effect size in planning VA Cooperative Study #590 (Li+)

AbstractBackgroundThe estimation of an effect size is an important step in designing an adequately powered, feasible clinical trial intended to change clinical practice. During the planning phase of VA Cooperative Study #590, “Double-Blind Placebo-Controlled Study of Lithium for Preventing Repeated Suicidal Self-Directed Violence in Patients with Depression or Bipolar Disorder (Li+),” it was not clear what effect size would be considered large enough to influence prescribing behavior among practicing clinicians.MethodsWe conducted an online survey of VA psychiatrists to assess their interest in the study question, their clinical experience with lithium, and their opinion about what suicide reduction rate would change their prescribing habits. The 9-item survey was hosted on SurveyMonkey© and VA psychiatrists were individually emailed an invitation to complete an anonymous online survey. Three email waves were sent over three weeks.ResultsOverall, 862 of 2713 VA psychiatrists (response rate = 31.8%) responded to the anonymous survey. 74% of the respondents would refer a patient to the proposed trial, 9% would not, and 17% were unsure. Presented with suicide reduction rates in 10% increments ranging from 10 to 100%, 61% of respondents indicated that they would use lithium if suicide attempts were reduced by at least 40%; 83% would use lithium if it reduced attempts by at least 50%.ConclusionsEven with the limitations of response bias and the reliability of responses on future prescribing behavior, a survey of potential users of a clinical trial's results offers a convenient, empirical method for determining and justifying clinically relevant effect sizes

Gender Differences in Demographic and Health Characteristics of the Million Veteran Program Cohort

The Department of Veterans Affairs Million Veteran Program (MVP) is the largest ongoing cohort program of its kind, with 654,903 enrollees as of June 2018. The objectives of this study were to examine gender differences in the MVP cohort with respect to response and enrollment rates; demographic, health, and health care characteristics; and prevalence of self-reported health conditions. The MVP Baseline Survey was completed by 415,694 veterans (8% women), providing self-report measures of demographic characteristics, health status, and medical history. Relative to men, women demonstrated a higher positive responder rate (23.0% vs. 16.0%), slightly higher enrollment rate (13.5% vs. 12.9%), and, among enrollees, a lower survey completion rate (59.7% vs. 63.8%). Women were younger, more racially diverse, had higher educational attainment, and were less likely to be married or cohabitating with a partner than men. Women were more likely to report good to excellent health status but poorer physical fitness, and less likely to report lifetime smoking and drinking than men. Compared with men, women veterans showed an increased prevalence of musculoskeletal conditions, thyroid problems, gastrointestinal conditions, migraine headaches, and mental health disorders, as well as a decreased prevalence of gout, cardiovascular diseases, high cholesterol, diabetes, and hearing problems. These results revealed some substantial gender differences in the research participation rates, demographic profile, health characteristics, and prevalence of health conditions for veterans in the MVP cohort. Findings highlight the need for tailoring recruitment efforts to ensure representation of the increasing women veteran population receiving care through the Veterans Health Administration

Gender Differences in Demographic and Health Characteristics of the Million Veteran Program Cohort

Background: The Department of Veterans Affairs Million Veteran Program (MVP) is the largest ongoing cohort program of its kind, with 654,903 enrollees as of June 2018. The objectives of this study were to examine gender differences in the MVP cohort with respect to response and enrollment rates; demographic, health, and health care characteristics; and prevalence of self-reported health conditions. Methods: The MVP Baseline Survey was completed by 415,694 veterans (8% women), providing self-report measures of demographic characteristics, health status, and medical history. Results: Relative to men, women demonstrated a higher positive responder rate (23.0% vs. 16.0%), slightly higher enrollment rate (13.5% vs. 12.9%), and, among enrollees, a lower survey completion rate (59.7% vs. 63.8%). Women were younger, more racially diverse, had higher educational attainment, and were less likely to be married or cohabitating with a partner than men. Women were more likely to report good to excellent health status but poorer physical fitness, and less likely to report lifetime smoking and drinking than men. Compared with men, women veterans showed an increased prevalence of musculoskeletal conditions, thyroid problems, gastrointestinal conditions, migraine headaches, and mental health disorders, as well as a decreased prevalence of gout, cardiovascular diseases, high cholesterol, diabetes, and hearing problems. Conclusions: These results revealed some substantial gender differences in the research participation rates, demographic profile, health characteristics, and prevalence of health conditions for veterans in the MVP cohort. Findings highlight the need for tailoring recruitment efforts to ensure representation of the increasing women veteran population receiving care through the Veterans Health Administration

Gender Differences in Demographic and Health Characteristics of the Million Veteran Program Cohort

BackgroundThe Department of Veterans Affairs Million Veteran Program (MVP) is the largest ongoing cohort program of its kind, with 654,903 enrollees as of June 2018. The objectives of this study were to examine gender differences in the MVP cohort with respect to response and enrollment rates; demographic, health, and health care characteristics; and prevalence of self-reported health conditions.MethodsThe MVP Baseline Survey was completed by 415,694 veterans (8% women), providing self-report measures of demographic characteristics, health status, and medical history.ResultsRelative to men, women demonstrated a higher positive responder rate (23.0% vs. 16.0%), slightly higher enrollment rate (13.5% vs. 12.9%), and, among enrollees, a lower survey completion rate (59.7% vs. 63.8%). Women were younger, more racially diverse, had higher educational attainment, and were less likely to be married or cohabitating with a partner than men. Women were more likely to report good to excellent health status but poorer physical fitness, and less likely to report lifetime smoking and drinking than men. Compared with men, women veterans showed an increased prevalence of musculoskeletal conditions, thyroid problems, gastrointestinal conditions, migraine headaches, and mental health disorders, as well as a decreased prevalence of gout, cardiovascular diseases, high cholesterol, diabetes, and hearing problems.ConclusionsThese results revealed some substantial gender differences in the research participation rates, demographic profile, health characteristics, and prevalence of health conditions for veterans in the MVP cohort. Findings highlight the need for tailoring recruitment efforts to ensure representation of the increasing women veteran population receiving care through the Veterans Health Administration