Clinical Trial Eligibility Criteria Research Articles

Poor prognosis germ-cell tumors: An unresolved challenge.

The prognostic classification developed by the International Germ Cell Consensus group (IGCCC) enables appropriate choice of initial treatment, and provides consistent eligibility criteria for clinical trials and more accurate assessment of published results. The standard therapy for IGCCC poor- and intermediate-prognosis germ-cell tumors is 4 cycles of bleomycin, etoposide, and cisplatin chemotherapy followed by surgical resection of residual masses, if the serum tumor markers have returned to normal. Improved outcomes are achieved by centers that treat a larger number of cases. The unsatisfactory results achieved with current therapy warrant entry of these patients into appropriate clinical trials. Future improvements in therapy are likely to require a better understanding of the molecular mechanisms of resistance and the development of novel therapeutic approaches that target these mechanisms.

Selecting subjects for participation in clinical research: one sphere of justice.

Recent guidelines from the US National Institutes of Health (NIH) mandate the inclusion of adequate numbers of women in clinical trials. Ought such standards to apply internationally? Walzer's theory of...

Apples and oranges: building a consensus for standardized eligibility criteria and end points in prostate cancer clinical trials.

To survey eligibility and response criteria for clinical trials in hormone-refractory prostate cancer (HRPC). Thirty-five established investigators of HRPC completed a 125-question survey. There was a general consensus that criteria for clinical trial entry would include progression based on an increasing prostate-specific antigen (PSA) level (94% of investigators), an increase in measurable disease (91%), and/or appearance of new bone lesions on bone scan (83%). Most believed that castrate levels of testosterone (77%) and progression after antiandrogen withdrawal (97%) should be documented before study enrollment. Continuation of testicular androgen suppression would be required by 82%. Seventy-seven percent favored separate reports on response rates in bone, measurable disease, symptoms, and biochemical markers (primarily PSA levels), rather than a composite response. Ninety-four percent of the investigators accepted changes in PSA level as a surrogate end point of response. However, interpretation by these investigators of a PSA data set similar to what might be observed in a clinical trial showed marked discordance. Survival is the end point of most importance to 94% of these investigators. Response based on changes in measurable disease, time to progression, response duration, PSA level decrease, or quality-of-life improvement were of similar weighted value as a clinical trial end point and were rated as less important to these investigators than survival (P < 10(-8)). This survey indicates some consensus on eligibility and concomitant treatments for clinical studies in HRPC. The use of multiparameter assessment of response and PSA level as a surrogate end point have been widely adopted.

Thoracoscopic evaluation of histologically/cytologically proven or suspected lung cancer: a VATS exploration

To evaluate the diagnostic value of video-assisted thoracic surgery (VATS), VATS exploration was performed in 135 patients with histologically/cytologically proven or suspected lung cancer. In 31 patients with pulmonary nodules suspected to be lung cancer, VATS exploration was intended to determine their histology by wedge resection. A histological diagnosis was made in all of the patients: 12 lung cancers (38.7%), 12 inflammatory granulomas (38.7%), four hamartomas (12.9%), and three others. VATS exploration (staging) was performed in 116 surgical candidates with documented lung cancer, including the 12 patients diagnosed by VATS wedge resection. Inoperable factors were demonstrated by this procedure in five patients (4.3%): malignant effusion without dissemination in three, malignant effusion with extensive dissemination in one, and extensive dissemination without effusion in one. Furthermore, N2 nodal metastasis at Botallo's ligament was demonstrated by this procedure in two patients, which met the eligibility criteria for a clinical study. Although the documented number of patients was relatively small, VATS exploration obviated the need for painful thoracotomy, selecting better treatment and for evaluating eligibility criteria for prospective clinical trials. The results suggest that this procedure is useful in candidates for lung cancer surgery.

Reducing patient eligibility criteria in cancer clinical trials.

To discuss patient eligibility criteria in phase III cancer clinical trials in the larger setting of the complexity of these trials, to review the various reasons for imposing restrictive eligibility requirements, to discuss the problems caused by these requirements, to argue that these requirements should be greatly relaxed in most cancer clinical trials, to provide some guiding principles and practical suggestions to facilitate such a relaxation, and to give an example of how eligibility requirements were reduced in a recent clinical trial in acute lymphocytic leukemia. Implicit and explicit reasons for including eligibility criteria in clinical trials are reviewed. Safety concerns and sample size issues receive special attention. The types of problems restrictive eligibility criteria cause with respect to scientific interpretation, medical applicability, complexity, costs, and patient accrual are described. A list of three items that each eligibility criterion should meet in order to be included is proposed and applied to a recent trial in acute lymphocytic leukemia. Phase III clinical trials in cancer should have much broader eligibility criteria than the traditionally restrictive criteria commonly used. Adoption of less restrictive eligibility criteria for most studies would allow broader generalizations, better mimic medical practice, reduce complexity and costs, and permit more rapid accrual without compromising patient safety or requiring major increases in sample size.