More data released on 908.

OBJECTIVE: To assess whether publicly funded adult cancer trials satisfy the uncertainty principle, which states that physicians should enroll a patient in a trial only if they are substantially uncertain which of the treatments in the trial is most appropriate for the patient. This principle is violated if trials systematically favour either the experimental or the standard treatment. DESIGN: Retrospective cohort study of completed cancer trials, with randomisation as the unit of analysis. SETTING: Two cooperative research groups in the United States. STUDIES INCLUDED: 93 phase III randomised trials (103 randomisations) that completed recruitment of patients between 1981 and 1995. MAIN OUTCOME MEASURES: Whether the randomisation favoured the experimental treatment, the standard treatment, or neither treatment; effect size (outcome of the experimental treatment compared with outcome of the standard treatment) for each randomisation. RESULTS: Three randomisations (3%) favoured the standard treatment, 70 (68%) found no significant difference between treatments, and 30 (29%) favoured the experimental treatment. The average effect size was 1.20 (95% confidence interval 1.13 to 1.28), reflecting a slight advantage for the experimental treatment. CONCLUSIONS: In cooperative group trials in adults with cancer, there is a measurable average improvement in disease control associated with assignment to the experimental rather than the standard arm. However, the heterogeneity of outcomes and the small magnitude of the advantage suggest that, as a group, these trials satisfy the uncertainty principle.

Clinical Trials, Phase III as Topic↗

PubMed2004

Clinical management of treatment-experienced, HIV-infected patients with the fusion inhibitor enfuvirtide: consensus recommendations.

The introduction of enfuvirtide (FUZEON) represents an important advance in the treatment of therapy-experienced patients with HIV-1 infection. However, parenteral self-administration, and the advanced disease and antiretroviral experience of patients currently most needing enfuvirtide introduce unique usage considerations. Enfuvirtide has been shown to provide clinically relevant improvements in CD4 cell counts and reductions in HIV viraemia across all subgroups of treatment-experienced patients studied, including those taking few or no other active drugs. However, optimal outcome results from initiation when the CD4 cell count is above 100 x 10(6) cells/l and viraemia below 1 x 10(5) copies/ml, as part of a newly constructed third or fourth antiretroviral regimen in combination with one or two other antiretrovirals to which the virus remains sensitive. Resistance testing should be used where available to guide background drug selection. Where insufficient options for an effective background exist, enfuvirtide should still be considered and treatment undertaken with the aim of achieving an immunological or clinical response, despite the unlikelihood of a sustained virological outcome. Similarly, where there is no viable alternative treatment, enfuvirtide should be continued following virological failure wherever ongoing immunological or clinical benefit is discerned. Injection site reactions (ISRs) are common on enfuvirtide and will affect almost all patients. ISRs are manageable and seldom activity- or treatment-limiting. Bacterial pneumonia and systemic hypersensitivity reactions have also been reported uncommonly. A structured series of patient visits with a healthcare professional provides an atmosphere of ongoing training and support that may prevent 'injection fatigue', maintain adherence and minimise the incidence of ISRs. An initial investment in establishing such procedures can be expected to yield significant returns in patient confidence and benefit on enfuvirtide.

Clinical Trials, Phase III as Topic↗