Medical Research Council Trials

MRC Working Party. Medical Research Council trial of treatment of hypertension in older adults principal results. BMJ 1992 304(6824) 405-12. 

Chessells JM, Bailey C, Richards SM. Intensification of treatment and survival in all children with lymphoblastic leukaemia results of UK Medical Research Council trial UKALL X. Medical Research Council Working Party on Childhood Leukaemia. Lancet 1995 345 143-148. 

Abbreviations CA, carotid atherosclerosis CPIHD, Caerphilly Prospective Ischemic Heart Disease EVCS, Elderly Vitamin C Status IWHS-D, Lowa Women s Health Study MGH, Mortality in a Geriatric Hospital MRCT Medical Research Council Trial NAHNES I, National Health and Nutrition Examination Survey PSCHD, Prospective Study of vitamin C in Coronary Heart Disease SOP Supplementation... 

I 59 Fletcher AE, Breeze E, Shetty PS. Antioxidant vitamins and mortality in older persons finding from the nutrition add-on study to the Medical Research Council Trial of Assessment and Management of Older People in the Community. Am J Clin Nutr 2003 78 999-1010. 

It is worth mentioning that two of the largest, most influential and independently funded early trials found little difference between the antidepressants tested and placebo. In the Medical Research Council trial comparing imipramine, phenelzine, ECT and placebo conducted in the United Kingdom (Medical Research Council 1965), it is well known that phenelzine performed poorly. However differences between... 

Medical Research Council Working Party on Mild Hypertension. Coronary heart disease in the Medical Research Council trial of treatment of mild hypertension. Br Heart J 1988 59(3) 364-78. 

Medical Research Council Prostate Cancer Working Party Investigators Group. Immediate versus deferred treatment for advanced prostate cancer Initial results of the Medical Research Council Trial. Br J Urol... 

Brompton Hospital/Medical Research Council Collaborative Trial, Br. Med. J. 4, 383 (1972). 

Medical Research Council Streptomycin in Tuberculosis Trials Committee. Streptomycin treatment for pulmonary tuberculosis. Br Med J 1948 ii 769-82. 

Brada M, Thomas DGT, Bleehan NM. Medical Research Council (MRC) randomized trial of adjuvant chemotherapy in high grade glioma (HGG). ProcAm Soc Clin Oncol 1998 17 400. 

Stephens RJ, Girling DJ, Bleehen NM, et al. The role of post-operative radiotherapy in non-small-cell lung cancer A multicentre randomized trial in patients with pathologically staged Tl-2, Nl-2, MO disease. Medical Research Council Lung Cancer Working Party. BrJ Cancer 1996 74 632-639. 

Fox W, Scadding JG. Medical Research Council comparative trial of surgery and radiotherapy for primary treatment of small-celled or oat-celled carcinoma of bronchus Ten-year follow-up. Lancet 1973 2 63-65. 

Clark PI, Medical Research Council. Randomized Trial of Surgery with or without Pre-Operative Chemotherapy in Resectable Cancer of the Esophagus. Ann Oncol 2000 11 4. 

There are several possible reasons for the negative results of this trial. One possibility is that an insufficient amount of chemotherapy was administered. Few would argue that two cycles of chemotherapy is likely insufficient to eradicate microscopic metastatic disease. However, in a 975 patient trial conducted by the Medical Research Council and the European Organization for the Research and Treatment of Cancer, three cycles of CMV given prior to definitive therapy failed to provide the 10% improvement in survival that could have been detected by the trial (43). Similarly, other trials of neoadjuvant chemotherapy to date have similarly not shown any obvious improvement in survival (70-739, so it is unlikely that the number of cycles of therapy here had a significant impact on the outcome of the study. Even if more cycles could have had an impact, it should be remembered that this trial was stopped early because of chemotherapy-related treatment deaths with only two cycles of treatment. Others... 

Medical Research Council Advanced Bladder Cancer Working Party. Neoadjuvant cisplatin, methotrexate, and vinblastine chemotherapy for muscle-invasive bladder cancer a randomised controlled trial. Lancet 1999 354 533-540. 

Mitchell CD, Richards SM, Kinsey SE. Medical Research Council Childhood Leukaemia Working Party. Benefit of dexamethasone compared with prednisolone for childhood acute lymphoblastic leukaemia results of the UK Medical Research Council ALL97 randomized trial. Br J Haematol 2005 129 734-745. 

Vora A, Mitchell CD, Lennard L et al. Medical Research Council. National Cancer Research Network Childhood Leukaemia Working Party. Toxicity and efficacy of 6-thioguanine versus 6-mercaptopurine in childhood lymphoblastic leukaemia a randomised trial. Lancet 2006 368 1339-1348. 

Medical Research Council Working Party. MRC trial of treatment of mild hypertension principal results. BMJ (Clin Res Ed) 1985 291(6488) 97-104. 

The technique of randomization was pioneered in the field of agriculture (plants too show considerable individual variation) by Sir Ronald Fisher, a visionary statistician. It is generally acknowledged that the first randomized clinical trial, conducted in the 1940s, was a study evaluating the use of streptomycin in treating tuberculosis conducted by the (British) Medical Research Council Streptomycin in Tuberculosis Trials Committee. The results were published in the British Medical Journal in 1948. 

B. Bden, J. LiLleyman, M. P. Shaw, et al. Medical research council ghiirfimnd leukemia trial VTH compared with trials II-V1I lessons for future management /femora/. Blood Tran tdon 50 448 (1967),... 

He pointed out that it had never been systematically evaluated, and that there were no studies that had attempted to control for these dramatic effects. A Medical Research Council funded randomised trial conducted in the United Kingdom in the 1950s appeared to support his conclusion when it found insulin coma produced no better outcome than a barbiturate-induced sleep used as a control procedure (Ackner, Harris, Oldham 1957). 

Medical Research Council 1965, Clinical trial of the treatment of depressive illness., Br.Med.J., vol. 1, pp. 881-886. 

LaRue LJ, Alter M, Traven ND et al. (1988). Acute stroke therapy trials problems in patient accrual. Stroke 19 950-954 Marshall M, Lockwood A, Bradley C et al. (2000). Unpublished rating scales a major source of bias in randomised controlled trials of treatments for schizophrenia British Journal of Psychiatry 176 249-252 Medical Research Council Working Party (1985). MRC trial of treatment of mild... 

The more pragmatic Medical Research Council Asymptomatic Carotid Surgery Trial (ACST) has probably produced more widely generalizable results (Halliday et al. 2004). Between 1993 and 2003, ACST randomized 3120 patients with > 60% mainly asymptomatic carotid stenosis (12% had symptoms at least six months previously) to immediate endarterectomy plus medical treatment versus medical treatment alone or until the operation became necessary. Surgeons were required to provide evidence of an operative risk of 6%... 

The Medical Research Council s General Practice Research Framewcxk. Thrombosis prevention trial ... 

Meade TW, Brennan PJ, Wilkes HC, Znhrie SR. Thrombosis prevention trial randomised trial of low-intensity oral anticoagulation with warfarin and low-dose aspirin in the primary prevention of ischaemic heart disease in men at increased risk. The Medical Research Council s General Practice Research Framework. Lancet 1998 351(9098) 233-41. 

In the UK Medical Research Council (MRC) trial, the outcome of antihypertensive treatment based on diuretics was compared with placebo in a very large number of hypertensive subjects (11). Treatment based on a thiazide did not increase the incidence of coronary events or sudden death indeed, thiazide-based treatment reduced the incidence of strokes by 67% and of all cardiovascular complications by 20%. It should be noted that the dose of bendroflumethiazide used in the MRC trial (lOmg/day) is now known to be unnecessarily high and that it was used without prophylaxis against hypokalemia. Even so, a subgroup analysis of data from the MRC Trial provided no evidence that the association between major electrocardiographic abnormalities and an increased likelihood of a clinical event was strengthened by bendroflumethiazide treatment (12). 

Singapore Tuberculosis Service and British Medical Research Council. Controlled trial of intermittent regimens of rifampicin plus isoniazid for pulmonary tuberculosis in Singapore. Lancet 1975 2(7945) 1105-9. 

An important trial funded by the UK Medical Research Council ( CAMS study) has explored the effects of synthetic THC (Marinol) and a cannabis extract ( Can-nador ) given orally on spasticity and other symptoms related to multiple sclerosis (Zajicek et al. 2003). This was a randomised, placebo-controlled trial involving 33 centres and 630 patients, and the primary outcome measure was change in overall spasticity score as represented by the Ashworth scale. 

Three landmark placebo-controlled clinical trials have established the benefits of both hypertension treatment and diuretic therapy. The Systolic Hypertension in the Elderly Program (SHEP), the Swedish Trial in Old Patients with Hypertension (STOP-Hypertension), and the Medical Research Council (MRC) trial " showed significant reductions in stroke, myocardial infarction, and aU-cause cardiovascular disease and mortality with thiazide diuretic-based therapy versus placebo. These trials allowed for /3-blockers as add-on therapy for BP control. Newer agents (i.e., ACE inhibitors, angiotensin II receptor blockers [ARBs], and calcium channel blockers [CCBs]) were not available at the time of these studies. However, subsequent clinical trials have compared these newer antihypertensive agents (ACE inhibitors, ARBs, and CCBs) to diuretics." These data show similar effects, but most trials used a prospective, open-label, blinded end point (PROBE) study methodology that is... 

Prince MJ, Bird AS, Blizard RA, Mann AH. Is the cognitive function of older patients affected by antihypertensive treatment Results from 54 months of the Medical Research Council s trial of hypertension in older adults. BMJ 1996 312 801-805. 

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