Comparison of outcomes in cancer patients treated within and outside clinical trials: conceptual framework and structured review

• Published in: The Lancet (British edition) 2004-01, Vol.363 (9405), p.263-270
• Main Authors: Peppercorn, Jeffrey M, Weeks, Jane C, Cook, E Francis, Joffe, Steven
• Format: Article
• Language: English
• Subjects: Antineoplastic agents; Bioethics; Biological and medical sciences; Cancer; Chemotherapy; Clinical outcomes; Clinical trial. Drug monitoring; Clinical trials; Clinical Trials as Topic - statistics & numerical data; Cohort Studies; General pharmacology; Hematology; Humans; Medical sciences; Medical treatment; Models, Theoretical; Neoplasms - therapy; Outcome Assessment (Health Care) - statistics & numerical data; Patient Selection; Patients; Pharmacology. Drug treatments; Randomized Controlled Trials as Topic - statistics & numerical data; Retrospective Studies; Treatment Outcome
• ISSN: 0140-6736; 1474-547X
• DOI: 10.1016/S0140-6736(03)15383-4

Many oncologists believe that patients with cancer who enrol in clinical trials have better outcomes than those who do not enrol. We aimed to assess the empirical evidence that such a trial effect exists. We developed a conceptual framework for comparison of trial and non-trial patients. We then did a comprehensive literature search to identify studies that compared outcomes between these groups. We critically evaluated these studies to assess whether they provide valid and generalisable support for a trial effect. We identified 26 comparisons, from 24 published articles, of outcomes among cancer patients enrolled and not enrolled in clinical trials. 21 comparisons used retrospective cohort designs. 14 comparisons provided some evidence that patients enrolled in trials have improved outcomes. However, strategies to control for potential confounding factors were inconsistent and frequently inadequate. Only eight comparisons restricted non-trial patients to those meeting trial eligibility criteria. Of these, three noted better outcomes in trial patients than in non-trial patients. Children with cancer, patients with haematological malignant disease, and patients treated before 1986 were disproportionately represented in positive studies. Despite widespread belief that enrolment in clinical trials leads to improved outcomes in patients with cancer, there are insufficient data to conclude that such a trial effect exists. Until such data are available, patients with cancer should be encouraged to enrol in clinical trials on the basis of trials' unquestioned role in improving treatment for future patients.