Core Outcome Measures in Effectiveness Trials

Definitions, End Points, and Clinical Trial Designs for Non-Muscle-Invasive Bladder Cancer: Recommendations From the International Bladder Cancer Group

General Information

Abstract:
PURPOSE: To provide recommendations on appropriate clinical trial designs in non-muscle-invasive bladder cancer (NMIBC) based on current literature and expert consensus of the International Bladder Cancer Group. METHODS: We reviewed published trials, guidelines, meta-analyses, and reviews and provided recommendations on eligibility criteria, baseline evaluations, end points, study designs, comparators, clinically meaningful magnitude of effect, and sample size. RESULTS: NMIBC trials must be designed to provide the most clinically relevant data for the specific risk category of interest (low, intermediate, or high). Specific eligibility criteria and baseline evaluations depend on the risk category being studied. For the population of patients for whom bacillus Calmette-Guerin (BCG) has failed, the type of failure (BCG unresponsive, refractory, relapsing, or intolerant) should be clearly defined to make comparisons across trials feasible. Single-arm designs may be relevant for the BCG-unresponsive population. Here, a clinically meaningful initial complete response rate (for carcinoma in situ) or recurrence-free rate (for papillary tumors) of at least 50% at 6 months, 30% at 12 months, and 25% at 18 months is recommended. For other risk levels, randomized superiority trial designs are recommended; noninferiority trials are to be used sparingly given the large sample size required. Placebo control is considered unethical for all intermediate- and high-risk strata; therefore, control arms should comprise the current guideline-recommended standard of care for the respective risk level. In general, trials should use time to recurrence or recurrence-free survival as the primary end point and time to progression, toxicity, disease-specific survival, and overall survival as potential secondary end points. Realistic efficacy thresholds should be set to ensure that novel therapies receive due review by regulatory bodies. CONCLUSION: The International Bladder Cancer Group has developed formal recommendations regarding definitions, end points, and clinical trial designs for NMIBC to encourage uniformity among studies in this disease.

Authors:
Kamat, A. M. Sylvester, R. J. Bohle, A. Palou, J. Lamm, D. L. Brausi, M. Soloway, M. Persad, R. Buckley, R. Colombel, M. Witjes, J. A.

Publication

Journal:
Journal of Clinical Oncology
Volume:
34
Issue:
16
Pages:
1935 - 44
Year:
2016
DOI:
Further Study Information

Date:
Funding source(s):

Health Area

Disease Category
Cancer

Disease Name
Bladder cancer

Target Population

Age Range
-

Sex
Either


Nature / type of Intervention
Any

Method(s)

Semi structured discussion
Systematic review

We met on 3 separate days, with discussions focused on patient eligibility criteria, baseline evaluations, efficacy end points, study designs, ideal comparators, appropriate sample sizes, and the magnitude of effect that would be considered clinically meaningful. Recommendations provided are based on amalgamation of the literature that the group deemed relevant as well as on group consensus and expert opinion. finalize the COS. The EWG split into small groups of subject-specific experts to determine how, when and by whom each outcome would be measured.


Stakeholders Involved

Clinical experts
Researchers

Study Type

COS for clinical trials or clinical research

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