Cochrane Collaboration

About: Cochrane Collaboration is a nonprofit organization based out in Oxford, United Kingdom. It is known for research contribution in the topics: Systematic review & Randomized controlled trial. The organization has 1995 authors who have published 3928 publications receiving 382695 citations.

Pioglitazone for type 2 diabetes mellitus

Abstract: Background Diabetes has long been recognised as a strong, independent risk factor for cardiovascular disease, a problem which accounts for approximately 70% of all mortality in people with diabetes. Prospective studies show that compared to their non-diabetic counterparts, the relative risk of cardiovascular mortality for men with diabetes is two to three and for women with diabetes is three to four. The two biggest trials in type 2 diabetes, the United Kingdom Prospective Diabetes Study (UKPDS) and the University Group Diabetes Program (UGDP) study did not reveal a reduction of cardiovascular endpoints through improved metabolic control. Theoretical benefits of the newer peroxisome proliferator activated receptor gamma (PPAR-gamma) activators like pioglitazone on endothelial function and cardiovascular risk factors might result in fewer macrovascular disease events in people with type 2 diabetes mellitus. Objectives To assess the effects of pioglitazone in the treatment of type 2 diabetes. Search strategy Studies were obtained from computerised searches of MEDLINE, EMBASE and The Cochrane Library. The last search was conducted in August 2006. Selection criteria Studies were included if they were randomised controlled trials in adult people with type 2 diabetes mellitus and had a trial duration of at least 24 weeks. Data collection and analysis Two authors independently assessed trial quality and extracted data. Pooling of studies by means of random-effects meta-analysis could be performed for adverse events only. Main results Twenty-two trials which randomised approximately 6200 people to pioglitazone treatment were identified. Longest duration of therapy was 34.5 months. Published studies of at least 24 weeks pioglitazone treatment in people with type 2 diabetes mellitus did not provide convincing evidence that patient-oriented outcomes like mortality, morbidity, adverse effects, costs and health-related quality of life are positively influenced by this compound. Metabolic control measured by glycosylated haemoglobin A1c (HbA1c) as a surrogate endpoint did not demonstrate clinically relevant differences to other oral antidiabetic drugs. Occurrence of oedema was significantly raised. The results of the single trial with relevant clinical endpoints (Prospective Pioglitazone Clinical Trial In Macrovascular Events--PROactive study) have to be regarded as hypothesis-generating and need confirmation. Authors' conclusions Until new evidence becomes available, the benefit-risk ratio of pioglitazone remains unclear. Different therapeutic indications for pioglitazone of the two big U.S. and European drug agencies should be clarified to reduce uncertainties amongst patients and physicians.

Diagnostic therapeutic flow-charts for low back pain patients: the Italian clinical guidelines

Abstract: I 2002 the Italian Health Ministry (IHM) financed the Care and Research Institute (IRCCS) Fondazione Don Carlo Gnocchi ONLUS of Milan to carry out a research project entitled: “Percorsi diagnostico-terapeutici evidence-based per le patologie del rachide lombare” (Evidence-based diagnostic therapeutic flow-charts (DTF) for lumbar spine pathologies).1 The first Operative Unit of this project was assigned the task of creating a National Committee which would include all Scientific Societies representing a medical speciality and/or health profession facing problems of the lumbar spine (Appendix).1 This Committee prepared Italian DTFs, the purpose of which was to act as a single scientific and cultural benchmark for every local initiative of development of DTF, as advised by the IHM.2 The DTF, that were produced in a strictly evidence-based way, have been considered by the IHM a subsequent step, more concrete and operative (almost clinical-care profiles) with respect to the classic Guidelines. In recent years, the guidelines have become an essential means for synthesizing results proposed in the scientific literature and making them fully available to physicians.3-7 Presently, there are numerous examples of guidelines in the field of low back pain (LBP) 4-11 and experience gained allows us to affirm, on one

Treatment success in cancer: new cancer treatment successes identified in phase 3 randomized controlled trials conducted by the National Cancer Institute-sponsored cooperative oncology groups, 1955 to 2006.

Abstract: Background The evaluation of research output, such as estimation of the proportion of treatment successes, is of ethical, scientific, and public importance but has rarely been evaluated systematically. We assessed how often experimental cancer treatments that undergo testing in randomized clinical trials (RCTs) result in discovery of successful new interventions. Methods We extracted data from all completed (published and unpublished) phase 3 RCTs conducted by the National Cancer Institute cooperative groups since their inception in 1955. Therapeutic successes were determined by (1) assessing the proportion of statistically significant trials favoring new or standard treatments, (2) determining the proportion of the trials in which new treatments were considered superior to standard treatments according to the original researchers, and (3) quantitatively synthesizing data for main clinical outcomes (overall and event-free survival). Results Data from 624 trials (781 randomized comparisons) involving 216 451 patients were analyzed. In all, 30% of trials had statistically significant results, of which new interventions were superior to established treatments in 80% of trials. The original researchers judged that the risk-benefit profile favored new treatments in 41% of comparisons (316 of 766). Hazard ratios for overall and event-free survival, available for 614 comparisons, were 0.95 (99% confidence interval [CI], 0.93-0.98) and 0.90 (99% CI, 0.87- 0.93), respectively, slightly favoring new treatments. Breakthrough interventions were discovered in 15% of trials. Conclusions Approximately 25% to 50% of new cancer treatments that reach the stage of assessment in RCTs will prove successful. The pattern of successes has become more stable over time. The results are consistent with the hypothesis that the ethical principle of equipoise defines limits of discoverability in clinical research and ultimately drives therapeutic advances in clinical medicine.

Long-acting beta2-agonists for chronic obstructive pulmonary disease.

Abstract: Background Chronic obstructive pulmonary disease (COPD) is a respiratory disease that causes progressive symptoms of breathlessness, cough and mucus build-up. It is the fourth or fifth most common cause of death worldwide and is associated with significant healthcare costs. Inhaled long-acting beta2-agonists (LABAs) are widely prescribed to manage the symptoms of COPD when short-acting agents alone are no longer sufficient. Twice-daily treatment with an inhaled LABA is aimed at relieving symptoms, improving exercise tolerance and quality of life, slowing decline and even improving lung function and preventing and treating exacerbations. Objectives To assess the effects of twice-daily long-acting beta2-agonists compared with placebo for patients with COPD on the basis of clinically important endpoints, primarily quality of life and COPD exacerbations. Search methods We searched the Cochrane Airways Group trials register, ClinicalTrials.gov and manufacturers’ websites in June 2013. Selection criteria Parallel, randomised controlled trials (RCTs) recruiting populations of patients with chronic obstructive pulmonary disease. Studies were required to be at least 12 weeks in duration and designed to assess the safety and efficacy of a long-acting beta2-agonist against placebo. Data collection and analysis Data and characteristics were extracted independently by two review authors, and each study was assessed for potential sources of bias. Data for all outcomes were pooled and subgrouped by LABA agent (formoterol 12 μg, formoterol 24 μg and salmeterol 50 μg) and then were separately analysed by LABA agent and subgrouped by trial duration. Sensitivity analyses were conducted for the proportion of participants taking inhaled corticosteroids and for studies with high or uneven rates of attrition. Main results Twenty-six RCTs met the inclusion criteria, randomly assigning 14,939 people with COPD to receive twice-daily LABA or placebo. Study duration ranged from three months to three years; the median duration was six months. Participants were more often male with moderate to severe symptoms at randomisation; mean forced expiratory volume in 1 second (FEV1) was between 33% and 55% predicted normal in the studies, and mean St George’s Respiratory Questionnaire score (SGRQ) ranged from 44 to 55 when reported. Moderate-quality evidence showed that LABA treatment improved quality of life on the SGRQ (mean difference (MD) -2.32, 95% confidence interval (CI) -3.09 to -1.54; I2 = 50%; 17 trials including 11,397 people) and reduced the number of exacerbations requiring hospitalisation (odds ratio (OR) 0.73, 95% CI 0.56 to 0.95; I2 = 10%; seven trials including 3804 people). In absolute terms, 18 fewer people per 1000 were hospitalised as the result of an exacerbation while receiving LABA therapy over a weighted mean of 7 months (95% CI 3 to 31 fewer). Scores were also improved on the Chronic Respiratory Disease Questionnaire (CRQ), and more people receiving LABA treatment showed clinically important improvement of at least four points on the SGRQ. The number of people who had exacerbations requiring a course of oral steroids or antibiotics was also lower among those taking LABA (52 fewer per 1000 treated over 8 months; 95% CI 24 to 78 fewer, moderate quality evidence). Mortality was low, and combined findings of all studies showed that LABA therapy did not significantly affect mortality (OR 0.90, 95% CI 0.75 to 1.08; I2 = 21%; 23 trials including 14,079 people, moderate quality evidence). LABA therapy did not affect the rate of serious adverse events (OR 0.97, 95% CI 0.83 to 1.14; I2 = 34%, moderate quality evidence), although there was significant unexplained heterogeneity, especially between the two formoterol doses. LABA therapy improved predose FEV1 by 73 mL more than placebo (95% CI 48 to 98; I2 = 71%, low quality evidence), and people were more likely to withdraw from placebo than from LABA therapy (OR 0.74, 95% CI 0.69 to 0.80; I2 = 0%). Higher rates of withdrawal in the placebo arm may reduce our confidence in some results, but the disparity is more likely to reduce the magnitude of difference between LABA and placebo than inflate the true effect; removing studies at highest risk of bias on the basis of high and unbalanced attrition did not change conclusions for the primary outcomes. Authors’ conclusions Moderate-quality evidence from 26 studies showed that inhaled long-acting beta2-agonists are effective over the medium and long term for patients with moderate to severe COPD. Their use is associated with improved quality of life and reduced exacerbations, including those requiring hospitalisation. Overall, findings showed that inhaled LABAs did not significantly reduce mortality or serious adverse events.

Erythropoietin for patients with malignant disease

Abstract: Background Anaemia associated with cancer and cancer therapy is an important clinical factor in the treatment of malignant diseases. Therapeutic alternatives are recombinant human erythropoietin (EPO) and red blood cell transfusions. Objectives The aim of this systematic review was to assess the effect of erythropoietin to either prevent or treat anaemia in cancer patients. Search strategy We searched the Central Register of Controlled Trials, MEDLINE (01/1985 to 12/2001), EMBASE (01/1985 to 12/2001), other databases and reference lists of articles. We also contacted experts in the field and pharmaceutical companies. Selection criteria Randomised controlled trials comparing the use of recombinant human erythropoietin (plus transfusion if needed) with red blood cell transfusions alone for the treatment or prevention of anaemia in cancer patients. Data collection and analysis Two reviewers independently assessed trial quality and extracted data. All authors from included studies were contacted for additional information. Main results Twenty seven trials with 3,287 adults were included. Use of erythropoietin significantly reduced the relative risk of red blood cell transfusions (RR 0.67; 95% CI 0.62 to 0.73, 25 trials, n = 3,069). On average participants in the erythropoietin group received one unit of blood less than the control group (WMD -1.00; 95% CI-1.31 to -0.70, 13 trials, n = 2,056). For participants with baseline haemoglobin below 10 g/dL haematological response was observed more often in participants receiving EPO (RR 3.60; 95% CI 3.07 to 4.23, 14 trials, n = 2,347). There was inconclusive evidence whether EPO improves tumour response (fixed effect RR 1.36; 95% CI 1.07 to 1.72, seven trials, n = 1,150; random effects: RR 1.21; 95% CI 0.92 to 1.59) and overall survival (adjusted data: HR 0.81; 95% CI 0.67 to 0.99; unadjusted data: HR 0.84; 95% CI 0.69 to 1.02, 19 trials, n = 2,865). There were no statistically significant adverse effects. Evidence was inconclusive with respect to quality of life and fatigue. Reviewers' conclusions There is consistent evidence that the administration of erythropoietin reduces the risk for blood transfusions and the number of units transfused in cancer patients. For patients with baseline haemoglobin below 10 g/dL there is strong evidence that erythropoietin improves haematological response. There is inconclusive evidence whether erythropoietin improves tumour response and overall survival. Research on side effects is inconclusive.