The Application of Preference Elicitation Methods in Clinical Trial Design to Quantify Trade-Offs: A Scoping Review

Background and Objective: Patients can express preferences for different treatment options in a healthcare context, which can be measured with quantitative preference elicitation methods. Our objective was to conduct a scoping review to determine how preference elicitation methods have been used to design clinical trials. Methods: We conducted a scoping review to identify primary research studies involving any health condition, that used quantitative preference elicitation methods, including direct utility-based approaches, and stated preference studies, to value heath trade-offs in the context of clinical trial design. Studies were identified by screening existing systematic and scoping reviews, and a primary literature search in MEDLINE from 2010-present. We extracted study characteristics and the application of preference elicitation methods to clinical trial design according to the SPIRIT checklist from primary studies and summarized the findings descriptively. Results: We identified 18 eligible studies. The included studies applied patient preferences to 5 areas of clinical trial design: intervention selection (n=1), designing N-of-1 trials (n=1), outcome selection and weighting composite and ordinal outcomes (n=12), sample size calculations (n=2), and recruitment (n=2). Using preference elicitation methods led to different decisions being made, such as using preference-weighted composite outcomes instead of equally weighted composite outcomes. Conclusion: Preference elicitation methods are infrequently used to design clinical trials but may lead to changes throughout the trial which could impact the evidence generated. Future work should be done to consider measurement challenges and explore stakeholder perceptions.Canadian Institutes of Health Research (CIHR

Histologic Healing Rates of Medical Therapies for Ulcerative Colitis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

OBJECTIVES: Histologic remission is a potentially valuable means of assessing disease activity and treatment response in ulcerative colitis (UC). However, the efficacy of existing therapies to achieve this outcome is unclear. We performed a systematic review and meta-analysis of histologic outcomes in UC randomized controlled trials and examined the relationship between histologic and endoscopic outcomes. METHODS: MEDLINE, EMBASE, CENTRAL, and the Cochrane IBD Register were searched for randomized controlled trials of aminosalicylates, corticosteroids, immunosuppressives, biologics, and small molecules. Histologic and endoscopic remission and response data were independently extracted and pooled using binomial-normal random-effect or fixed-effect models. Pooled efficacy estimates were calculated as risk ratios (RRs) using the Mantel-Haenszel method. Univariable and multivariable random-effect meta-regression models examined factors associated with histologic remission. RESULTS: Seventy-four studies (68 induction and 7 maintenance) were identified. Topical aminosalicylate enemas [37.2%, 95% confidence interval (CI), 29.0-46.3] and suppositories (44.9%, 95% CI, 28.9-62.3) had the highest induction of histologic remission rates. Aminosalicylate enemas (RR = 4.14, 95% CI, 2.35-7.31), aminosalicylate suppositories (RR = 3.94, 95% CI, 1.26-12.32), and budesonide multimatrix (RR = 1.47, 95% CI 1.08-1.99) had higher histologic remission rates than placebo. Data were lacking for biologics and immunosuppressives. The pooled histologic remission rate for placebo in induction studies was 10.4% (95% CI, 7.1-15.2). Histologic and endoscopic remission correlated strongly (r = 0.66; 95% CI, 0.50-0.78). In multivariate analysis of placebo-arm data, less severe clinical disease activity and corticosteroid use were associated with higher histologic remission rates. Similarly, mild clinical disease activity was associated with higher histologic remission rates when active-arm data were analyzed. CONCLUSIONS: Histologic remission rates for current UC treatments ranged from 15.0% to 44.9% according to drug class and patient population with the highest rates observed for topical aminosalicylates. Placebo remission rates were low with relatively narrow CIs. These data provide benchmarks to inform future trial design. Histologic remission is a potential treatment target in clinical practice

Disease-modifying anti-rheumatic drugs for rheumatoid arthritis: A systematic review and network meta-analysis

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: The primary objective is to compare the benefits and harms of different disease‐modifying anti‐rheumatic drugs (DMARDs) as initial therapy and after failure of conventional synthetic DMARDs or biologic or targeted synthetic DMARDs in adults with rheumatoid arthritis through a network meta‐analysis (NMA). A secondary objective is to rank the interventions for both benefits and harms. This protocol describes the approach for separate NMAs for the three populations of interest (described below), which we intend to publish as three separate Cochrane Reviews. 1) Disease‐modifying anti‐rheumatic drugs for rheumatoid arthritis as initial therapy: a systematic review and network meta‐analysis 2) Disease‐modifying anti‐rheumatic drugs for rheumatoid arthritis after failure of conventional synthetic disease‐modifying anti‐rheumatic drugs: a systematic review and network meta‐analysis 3) Disease‐modifying anti‐rheumatic drugs for rheumatoid arthritis after failure of biologic or targeted synthetic therapy: a systematic review and network meta‐analysi