Notes

The dwelling overall performance of centriolar rootlets.
Restrictive eligibility criteria induce differences between clinical trial and "real-world" treatment populations. Restrictions based on prior therapies are common; minimizing them when appropriate may increase patient participation in clinical trials.

A multi-stakeholder working group developed a conceptual framework to guide evaluation of prevailing practices with respect to using prior treatment as selection criteria for clinical trials. Selleckchem JSH-150 The working group made recommendations to minimize restrictions based on prior therapies within the boundaries of scientific validity, patient centeredness, distributive justice, and beneficence.

(i) Patients are eligible for clinical trials regardless of the number or type of prior therapies and without requiring a specific therapy prior to enrollment unless a scientific or clinically based rationale is provided as justification. (ii) Prior therapy (either limits on number and type of prior therapies or requirements for specific therapies before enrollment) could be used to determine eligibility in the following cases a) the agents being studied target a specific mechanism or pathway that could potentially interact with a prior therapy; b) the study design requires that all patients begin protocol-specified treatment at the same point in the disease trajectory; and c) in randomized clinical studies, if the therapy in the control arm is not appropriate for the patient due to previous therapies received. (iii) Trial designers should consider conducting evaluation separately from the primary endpoint analysis for participants who have received prior therapies.

Clinical trial sponsors and regulators should thoughtfully reexamine the use of prior therapy exposure as selection criteria to maximize clinical trial participation.
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Clinical trial sponsors and regulators should thoughtfully reexamine the use of prior therapy exposure as selection criteria to maximize clinical trial participation.See related commentary by Giantonio, p. 2369.
In clinical research, eligibility criteria promote patient safety and optimize the evidence generated from clinical trials. However, overly stringent eligibility criteria, including laboratory requirements, may limit enrollment, resulting in delayed trial completion and potentially limiting applicability of trial results to a general practice population.

Starting in 2018, a working group consisting of experts in direct patient care, the FDA, industry, and patient advocacy developed recommendations to guide the optimal use of laboratory reference ranges and testing intervals in clinical trial eligibility criteria and study procedures. The working group evaluated current eligibility criteria across different clinical trial phases and performed a literature review to evaluate the impact of and justification for laboratory test eligibility requirements and testing intervals in clinical trials. Recommendations were developed on the basis of the goals of promoting safety and optimizing the evidence generated, while also expanding eligibility and applicability, and minimizing excess burden of trial participation.

In general, we found little variation over time and trial phase in laboratory test requirements, suggesting that these eligibility criteria are not refined according to ongoing clinical experience. We propose recommendations to optimize the use of laboratory tests when considering eligibility criteria.

Tailoring the use of laboratory test requirements and testing intervals may increase the number and diversity of patients in clinical trials and provide clinical data that more closely represent the general practice populations.
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Tailoring the use of laboratory test requirements and testing intervals may increase the number and diversity of patients in clinical trials and provide clinical data that more closely represent the general practice populations.See related commentary by Giantonio, p. 2369.
Washout periods and concomitant medication exclusions are common in cancer clinical trial protocols. These exclusion criteria are often applied inconsistently and without evidence to justify their use. The authors sought to determine how washout period and concomitant medication allowances can be broadened to speed trial enrollment and improve the generalizability of trial data to a larger oncology practice population without compromising the safety of trial participants.

A multistakeholder working group was convened to define problems associated with excessively long washout periods and exclusion of patients due to concomitant medications. The group performed a literature search and evaluated study data from the Pancreatic Cancer Action Network (PanCAN), Emory University School of Medicine (Atlanta, GA), and the FDA to understand recent approaches to these eligibility criteria. The group convened to develop consensus recommendations for broadened eligibility criteria.

The data analysis found that exclusion criteria based on washout periods and concomitant medications are frequently inconsistent and lack scientific rationale. Scientific rationale for appropriate eligibility criteria are presented in the article; for washout periods, rationale is presented by treatment type.

Arbitrary or blanket washout and concomitant medication exclusions should be eliminated. Where there is evidence to support them, clinically relevant washout periods and concomitant medication-related eligibility criteria may be included.
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Arbitrary or blanket washout and concomitant medication exclusions should be eliminated. Where there is evidence to support them, clinically relevant washout periods and concomitant medication-related eligibility criteria may be included.See related commentary by Giantonio, p. 2369.
Cancer clinical trials often accrue slowly or miss enrollment targets. Strict eligibility criteria are a major reason. Restrictive criteria also limit opportunities for patient participation while compromising external validity of trial results. We examined the impact of broadening select eligibility criteria on characteristics and number of patients eligible for trials, using recommendations of the American Society of Clinical Oncology (ASCO) and Friends of Cancer Research.

A retrospective, observational analysis used electronic health record data from ASCO's CancerLinQ Discovery database. Study cohort included patients with advanced non-small cell lung cancer treated from 2011 to 2018. Patients were grouped by traditional criteria [no brain metastases, no other malignancies, and creatinine clearance (CrCl) ≥ 60 mL/minute] and broadened criteria (including brain metastases, other malignancies, and CrCl ≥ 30 mL/minute).

The analysis cohort included 10,500 patients. Median age was 68 years, and 73% of patients were White.
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