Showing papers by "Clinical Trial Service Unit published in 1993"

Large-scale randomized evidence: large, simple trials and overviews of trials.

Abstract: Worldwide, hundreds of thousands of premature deaths a year could be avoided by seeking large-scale randomized evidence about various widely practicable treatments for the common causes of death, and by disseminating such evidence appropriately. Likewise, appropriately large-scale randomized evidence could vastly improve the management of many important, but non-fatal, medical problems. The chief techniques for obtaining large-scale randomized evidence are large, simple trials (or “mega-trials”) such as the ISIS [l-4] and GISSI [5,6] studies, and large systematic overviews of trials (or “meta-analyses”) such as those from the worldwide collaborative groups of trialists [7-91 or of meta-analysts [lo]. Over the past decade the introduction of these complementary techniques has already yielded a succession of striking and definite findings that have improved the treatment of millions of patients. But, what has been achieved so far is only a fraction of what could quite readily be achieved by the wholehearted pursuit of such research strategies. Inevitably, any review of the need for really large-scale randomized evidence has to discuss to some extent the general unreliability of nonrandomized evidence (whether this be called “historically controlled” evidence, “data-base analyses” or, more misleadingly, “outcomes research” or “effectiveness analysis”), and it has to discuss to some extent the general unreliabil-

Results of Medical Research Council trial UKALL IX in acute lymphoblastic leukaemia in adults: report from the Medical Research Council Working Party on Adult Leukaemia

Abstract: The MRC UKALL IX trial for patients with untreated ALL aged 14 years and over was open to new patients from July 1980 to April 1985. 266 patients were randomized between two induction schedules. M (involving intermediate dose methotrexate with folinic acid rescue) and D (involving daunorubicin). Schedule M resembled that used in the previous MRC adult ALL trial (UKALL VI), while schedule D was somewhat more intensive. No difference in disease-free survival was found between the treatment arms, but patients on the daunorubicin arm went into remission earlier. The overall remission rate was 87%, which is at least as good as in contemporary studies elsewhere; factors predictive of a lower remission rate were older age and higher WBC. For those who entered remission. WBC, age and sex were the most important prognostic factors. Time to achieve remission was not a significant factor after allowance was made for these. An historical comparison does not show any improvement over the preceding MRC adult trial, although the subsequent trial does show a modest improvement at present. Because the improved outlook seen in children is not apparent in adults, and no other randomized trial has demonstrated substantial benefit for any particular regimen, the next trial, UKALL XII, will be investigating the benefit or otherwise of bone marrow transplantation.