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Unlocking the full potential of clinical trials through comprehensive CSR and IPD sharing can revolutionize cancer care, enhance safety evaluations, and reduce bias in systematic reviews. It is time for all stakeholders to embrace transparency and advance patient-centered outcomes.

New systemic therapies have prolonged the lives of men with metastatic castration-resistant prostate cancer (mCRPC). Use of these therapies in the adjuvant setting when the disease may be micrometastatic and potentially more sensitive to therapies may decrease mortality from prostate cancer. However, the conduct of adjuvant prostate cancer clinical trials is hampered by taking longer than a decade to reach the meaningful endpoint of overall survival (OS) and the fact that many men never die from prostate cancer, even if they relapse. A validated intermediate clinical endpoint (ICE) in prostate cancer that is a robust surrogate for OS has yet to be defined. This paper details the plans, process, and progress of the international Intermediate Clinical Endpoints in Cancer of the Prostate (ICECaP) working group to pool individual patient data from all available clinical trials of radiation or prostatectomy for localized disease and conduct the requisite analyses to determine whether an ICE can be identified. This paper further details the challenges and the a priori statistical analytical plans and strategies to define an ICE for adjuvant prostate cancer clinical trials. In addition, a brief review of the health economic analyses to model the benefits to patients, society and manufacturers is detailed. If successful, the results from this work will provide a robust surrogate for OS that will expedite the design and conduct of future adjuvant therapy trials using new agents that have proven activity in mCRPC. Moreover, it will also define the health economic benefits to patients and societies., (© The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Objective: There are clear advantages to using biomarkers and surrogate endpoints, but concerns about clinical and statistical validity and systematic methods to evaluate these aspects hinder their efficient application. Our objective was to review the literature on biomarkers and surrogates to develop a hierarchical schema that systematically evaluates and ranks the surrogacy status of biomarkers and surrogates; and to obtain feedback from stakeholders., Methods: After a systematic search of Medline and Embase on biomarkers, surrogate (outcomes, endpoints, markers, indicators), intermediate endpoints, and leading indicators, a quantitative surrogate validation schema was developed and subsequently evaluated at a stakeholder workshop., Results: The search identified several classification schema and definitions. Components of these were incorporated into a new quantitative surrogate validation level of evidence schema that evaluates biomarkers along 4 domains: Target, Study Design, Statistical Strength, and Penalties. Scores derived from 3 domains the Target that the marker is being substituted for, the Design of the (best) evidence, and the Statistical strength are additive. Penalties are then applied if there is serious counterevidence. A total score (0 to 15) determines the level of evidence, with Level 1 the strongest and Level 5 the weakest. It was proposed that the term "surrogate" be restricted to markers attaining Levels 1 or 2 only. Most stakeholders agreed that this operationalization of the National Institutes of Health definitions of biomarker, surrogate endpoint, and clinical endpoint was useful., Conclusion: Further development and application of this schema provides incentives and guidance for effective biomarker and surrogate endpoint research, and more efficient drug discovery, development, and approval.

Background: The adequacy of overall survival (OS) as study end point in phase III trials for advanced solid tumors is questionable. The present review highlights the limits of OS as study end point to evaluate the efficacy of new drugs., Methods: Four phase III clinical trials comparing a fluorouracil-based regimen with the same regimen plus either CPT-11 or oxaliplatin in advanced colorectal cancer patients were reviewed. The primary aim of the critical assessment was to explain the lack of OS advantage observed in two of the four trials, despite the presence of increased response rate (RR) and time to progression (TTP). Four possible reasons for the lack of OS benefit (i.e. statistical power, cross-over, magnitude of the effect on RR and TTP, non-tumor-related deaths) were systematically reviewed in the trials, and the detectable 1-year OS difference, assuming a statistical power of 80%, was calculated for each., Results: None of these reasons for the lack of OS advantage in presence of RR and TTP benefits convincingly explained the results of the evaluated trials. Three of the four trials had roughly the same statistical power to detect 1-year OS differences, while the fourth trial was underpowered to detect realistic OS differences. The lack of OS advantage observed in the two oxaliplatin trials is therefore likely fortuitous, and due to lack of statistical power., Conclusions: Although increase in OS remains the ultimate goal of many clinical trials, the choice of OS benefit as a mandatory requirement to register new compounds can lead to a serious underestimation of a drug's real efficacy.

The Center for Birth Defects Information Services, a non-profit scientific collaborative formed to promote scientific and professional communication in birth defects and human genetics, operates a number of print and electronic information services designed to support clinical practice, education, and research. Unique among these services is Micro BDIS; a self-contained Birth Defects Information System for the personal computer. Subscribers are able to describe clinical cases or search criteria in a standardized language, as well as free text. The Micro BDIS evaluation facility then assists in the development of a differential diagnosis. Unusual cases that do not fit established diagnosis may be submitted to an Unknowns Registry.

The Center for Birth Defects Information Services currently provides information in birth defects to medical centers. The D/A facility is designed to facilitate differential diagnosis and is being tested in preparation for general use sometime in 1981. A third facility is planned to classify and assist in identification of now unnamed and undiagnosed birth defects. This project when fully operative will assist clinicians in all phases of birth defects diagnosis so that they provide more quickly needed information to patients and their families.