The revelation that data obtained for the US-based National Surgical Adjuvant Breast and Bowel Project (NSABP) from subjects enrolled at Hôpital Saint-Luc in Montreal was falsified has eroded public trust in research. Institutions can educate researchers and help prevent unethical research practices by establishing procedures to monitor research involving human subjects. Research monitoring encompasses four categories of activity: annual reviews of continuing research, monitoring of informed consent, monitoring of adherence to approved protocols and monitoring of the integrity of data. The (...) authors describe characteristics of research projects that may call for monitoring procedures in each category. The form taken by such monitoring depends on the nature of the protocol. Although appropriate research monitoring requires substantial investment of personnel and financial resources, it is required under guidelines regulating research involving human subjects in Canada. Research monitoring is a step forward in re-establishing public confidence in medical research. (shrink)

OBJECTIVE: Pilot study to characterize treatment differences between patients treated in clinical trials and those treated in a clinical setting. Previous studies have shown higher survival rates for participants in trials of cancer therapy. This difference is observed even after rates are adjusted for important covariates such as age and stage of disease. DESIGN: Retrospective chart review. SETTING: Oncology outpatient department in a tertiary care hospital. PATIENTS: Ninety women 18 to 70 years of age with early-stage breast cancer who were (...) diagnosed in 1990. Fifty-one of the women were treated through clinical trials and 39 were treated outside of clinical trials. OUTCOME MEASURES: Number of blood tests, telephone calls, clinic visits and imaging procedures as well as intensity of chemotherapy and use of radiation therapy. The age of the patient and the stage of disease were important covariates. RESULTS: After the analysis was controlled for patient age and stage of disease, patients treated through a clinical trial were more likely to receive standard-dose chemotherapy (p = 0.020, 95% confidence interval 1.20 to 200.73) and more frequent blood tests (p < 0.001, 95% confidence interval 1.02 to 1.13) than other patients treated in the clinic. CONCLUSIONS: Our results provide a plausible mechanism for the observed survival advantage for participants in clinical trials in oncology. Further study is called for. If these results are confirmed, they have important implications for informed consent to participate in clinical trials and for clinical practice. (shrink)

We studied changes in eligibility criteria--the largest impediment to patient accrual--in two samples of clinical trials. Trials from the NSABP (National Surgical Adjuvant Breast and Bowel Program) and POG (Pediatric Oncology Group) were analyzed. After eliminating duplications, the criteria in each protocol were enumerated and classified according to a novel schema. NSABP trials contained significantly more criteria than POG trials, and added precision criteria (making study populations homogeneous) at a faster rate than POG studies. The difference between NSABP studies (explanatory (...) trials) and POG studies (pragmatic trials) suggest that large numbers of eligibility criteria are not necessary for quality studies. We recommend that: (1) the inclusion/exclusion criteria distinction be abandoned; (2) eligibility criteria be explicitly justified; (3) the need for each criterion be assessed when new trials are planned; (4) criteria in phase III trials restricting patient accrual be minimized; and (5) further research be done to assess the impact of criteria on generalizability. (shrink)

In contrast to attempts that have been made to measure the clarity of reporting of the methods of clinical trials in journal articles, we report here an attempt to measure the accuracy of methods reporting. We focus in this article on eligibility criteria as a test case for the reporting of clinical trial methods. We examined the reporting of eligibility criteria in the protocol, methods paper (if applicable), journal article, and Clinical Alert for articles appearing in print between January 1988 (...) and September 1994 for which a Clinical Alert had been issued. Eligibility criteria were further classified into five categories in order to examine the content of information loss, if any. On average, 82% of protocol eligibility criteria were reported in methods papers. Journal articles and Clinical Alerts fared somewhat worse: 63% of criteria were reported in journal articles, 19% in Clinical Alerts. In all three categories of medical communication, the reporting of criteria that defined the study disease tended to be complete; reporting of criteria relating to trial precision, patient safety, legal and ethical concerns, and administrative considerations, was not complete. We found that criteria for clinical trial eligibility are frequently under-reported in medical communications. Moreover, some of the criteria omitted are of considerable clinical importance. We suggest that in the design phase of clinical trials, proposed eligibility criteria be scrutinized closely. Those criteria that survive this scrutiny and that have clinical import must be reported upon fully and accurately when communicating trial results. (shrink)

OBJECTIVE: To investigate whether eligibility criteria that exclude the elderly, persons with psychiatric disease, and persons with substance abuse problems from participation in randomized controlled trials (RCTs) are subjective and hence a source of variability in enrolment decisions and investigator uncertainty. DESIGN: Survey questionnaire. PARTICIPANTS: Cancer investigators from the United States and Canada. INTERVENTIONS: Investigators were presented with clinical vignettes from 3 patient categories--eligible, ineligible and uncertain--for each of 5 eligibility criteria--3 subjective and 2 objective--and were asked whether they would (...) enrol the patient in a trial and how sure they were of this decision. Demographic characteristics of the investigators were also collected. OUTCOME MEASURES: The difference in enrolment decisions between subjective and objective criteria, and the difference in the certainty associated with these decisions. RESULTS: Of 365 questionnaires sent out, 224 usable ones were returned. Compared with the objective criteria, the subjective criteria were associated with more variable enrolment decisions (p = 0.07 for the "eligible" scenario and p = 0.0001 for the "ineligible" and "uncertain" scenarios), and investigators were less sure about the decisions they made (p = 0.0001 for all scenarios). Demographic characteristics of the investigators failed to explain the observed differences. CONCLUSIONS: Subjective eligibility criteria may interfere with the conduct and interpretation of RCTs and, therefore, their use ought to be justified explicitly in the study protocol. RCT designers, funding agencies and research ethics boards have an important role in reviewing eligibility criteria for their necessity. (shrink)