Showing papers by "Peter C Gøtzsche published in 2000"

Non-steroidal anti-inflammatory drugs.

Abstract: Definition Non-steroidal anti-inflammatory drugs (NSAIDs) have anti-inflammatory, analgesic, and antipyretic effects and inhibit thrombocyte aggregation. The drugs have no documented effect on the disease process itself. Incidence/prevalence NSAIDs are widely used. Almost 10% of people in the Netherlands had used a non-aspirin NSAID in 1987; the overall use was 11 defined daily doses (see box) per 1000 persons a day.1 In Australia in 1994, overall use was 35 defined daily doses per 1000 persons a day, with 36% of the people receiving NSAIDs for osteoarthritis, 42% for sprain and strain or low back pain, and 4% for rheumatoid arthritis; 35% were aged over 60 years.2 Aims To reduce symptoms in rheumatic disorders; to avoid severe gastrointestinal adverse effects. Outcomes Primary outcomes: pain intensity, person's preference for one drug over another, global efficacy, and clinically significant gastrointestinal complications. Secondary outcomes: number of tender joints, perforation, gastrointestinal haemorrhage, dyspepsia, and ulcer detected by routine endoscopy. Defined daily dose : The assumed average daily dose for the main indication of a specified drug. The defined daily dose per 1000 population per day is an estimate of the proportion of that population receiving treatment with that drug. We searched Medline and the Cochrane Library in July 1999 for systematic reviews and randomised controlled trials (RCTs) that included at least 100 people. More than 100 meta-analyses and thousands of RCTs have compared various NSAIDs. Many trials are unpublished or published in sources that are not indexed in publicly available databases. The quality of the trials is variable and bias is common, both in the design and analysis of the trials, to such an extent that a systematic review identified false significant findings favouring new drugs over control drugs in 6% of trials.3 #### Interventions ##### Beneficial: NSAIDs in rheumatoid arthritis Misoprostol in high risk patients who …

Why we need a broad perspective on meta-analysis. It may be crucially important for patients.

Abstract: In the world of clinical trials and meta-analyses there is an important debate between the “lumpers” and the “splitters.” This relates to whether the overall findings of clinical trials and meta-analyses are the appropriate outcome to apply to individuals (lumping) or whether it is better to try to match the characteristics of particular patients to characteristics of subgroups within trials or meta-analyses (splitting). Although the splitters' view seems intuitively correct, there are usually substantial clinical and methodological advantages to lumping. The generalisability and usefulness of meta-analyses are increased considerably if the individual trials cover different patient populations, settings, and concomitant routine care. For example, when a meta-analysis showed that the use of human albumin increased mortality1 this result applied to all three groups of critically ill patients studied. For patients with hypovolaemia the difference was not conventionally significant (95% confidence interval for the odds ratio 0.99 to 3.15), but it would be wrong to interpret this result as meaning that clinicians should continue to give these patients albumin. Most significant results will disappear because of lack of power if trials in a meta-analysis are split up into a large enough number of subgroups. It is more relevant that the point estimates were similar …

Somatostatin or octreotide for acute bleeding oesophageal varices.

Abstract: BACKGROUND Somatostatin and its derivative, octreotide, are often used for emergency treatment of bleeding oesophageal varices in patients with cirrhosis of the liver. The placebo controlled trials have shown varying results, however, and their power has been quite low. An updated systematic review of a previously published meta-analysis was therefore performed. OBJECTIVES To study whether somatostatin or octreotide improve survival or reduce the number of blood transfusions in patients with suspected or verified acute or recently bleeding oesophageal varices. SEARCH STRATEGY MEDLINE and The Cochrane Library are searched every three months. Reference lists of articles and authors. SELECTION CRITERIA All randomised trials comparing somatostatin or octreotide with placebo or no treatment in patients suspected of acute bleeding from oesophageal varices. DATA COLLECTION AND ANALYSIS The effect variables extracted were: mortality, number of blood transfusions, number with balloon tamponade, number with initial haemostasis and number with rebleeding. Intention to treat analyses were conducted; a random effects analysis was preferred if there was significant heterogeneity between the trials (p<0.10). MAIN RESULTS The meta-analysis comprised 820 patients. The active drugs had no effect on survival; a total of 91 patients died in the experimental groups vs 85 patients in the control groups (odds ratio 1.04, 95% confidence interval (CI) 0.74 to 1.46). The number of transfusions was less with drugs, the difference between experimental and control therapy was 1.2 units of blood products saved per patient (95% CI 0. 8 to 1.6). There were no significant differences in use of balloon tamponade (odds ratio 0.59, 95% CI 0.21 to 1.70), number of patients failing initial haemostasis (odds ratio 0.66, 95% CI 0.32 to 1.37) or number with rebleeding (odds ratio 0.73, 95% CI 0.30 to 1.79). It should be noted, however, that the trials were heterogeneous with respect to these secondary variables. REVIEWER'S CONCLUSIONS The effect corresponded to one unit of blood saved per patient. This effect is small and treatment with these drugs in acute bleeding oesophageal varices is therefore of doubtful value. This does not suggest a need for further studies. On the other hand, the confidence interval for the effect on mortality was wide. Hence, a large placebo controlled trial is needed if one wishes to rule out the possibility that a worthwhile effect on mortality may have been overlooked.

Do patients with osteoarthritis get the clinical research they need

Abstract: The most obvious and laudable reason for doing clinical research is, of course, to benefit the patients. Other motives that are sometimes important are to earn money, to increase chances of getting the next post, to become famous, or to satisfy curiosity. Such incentives are not necessarily bad. Indeed, the high level of competition in healthcare research may very well be more innovative and productive—and therefore more beneficial to the patients—than more centralised research approaches. A particular piece of research may occasionally fulfil all five motives, but it would be the exception rather than the rule if research agendas overall matched even remotely what the patients need most. For example, according to the WHO, the combined investment in research and development into acute respiratory infections, diarrhoeal diseases, and tuberculosis—which kill over seven million people a year—amounts to 0.2% of global spending on health research and development, though these three diseases account for almost one fifth of the global disease burden.1 Most new interventions, by far, are developed by industry and it is no wonder that industry chooses to go where the market is. For common diseases in the developed world this leads to the development of an array of drugs belonging to the same therapeutic class. Clinical testing of all those drugs consumes a considerable amount of financial and human resources, and clinicians sometimes complain that their colleagues have “occupied” the patients by trivial trials of “me too drugs” for years to come, making it impossible to start trials of greater relevance to the patients. Is osteoarthritis an exception to this general state of affairs? In this issue of the Annals , Chard and colleagues review 50 years of research on interventions for osteoarthritis of the knee.2 They report that most of the research was on drugs (59%) …

Randomised clinical trials in the Scandinavian Journal of Rheumatology.

Abstract: Objective: To identify all reports of randomised clinical trials in the Journal and compare our findings with reports available in Medline. Methods: We handsearched the Scandinavian Journal of Rheumatology with supplements for the years 1955-1997 to identify reports of randomised clinical trials and controlled clinical trials. Results: We identified 445 trial reports. In Medline, 134 of these trials (30%) were indexed as randomised or controlled trials; an additional 50 trials (11%) were available in Medline but were indexed differently. Thus, 261 of the trials (59%) we identified were not indexed in Medline; most of these trials were published in supplements to the Journal. Conclusion: Handsearching of medical journals for randomised trials can be a worthwhile effort. Clinicians and patients will become better informed about the value of different treatment options and researchers will reduce their risk of performing trials that are unnecessary.