Is there a need to control the placebo in placebo controlled trials?
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Humans↗
Biomedical subjects
J Kleijnen
Publications and source records attributed to J Kleijnen.
Analgesic efficacy and safety of paracetamol-codeine combinations versus paracetamol alone: a systematic review.
OBJECTIVES: To assess whether adding codeine to paracetamol has an additive analgesic effect; to assess the safety of paracetamol-codeine combinations versus paracetamol alone. DESIGN: Systematic literature review with meta-analysis, methodological quality of published trials being scored by means of 13 predefined criteria. TRIALS: 24 of 29 trials that met the inclusion criteria. Models studied in the trials were postsurgical pain (21), postpartum pain (one), osteoarthritic pain (one), and experimentally induced pain (one). INTERVENTIONS: Dosages ranged from 400 to 1000 mg paracetamol and 10 to 60 mg codeine. MAIN OUTCOME MEASURES: The sum pain intensity difference (efficacy analysis) and the proportion of patients reporting a side effect (safety analysis). RESULTS: Most trials were considered of good to very good quality. Only the single dose studies could be combined for analysis of analgesic efficacy. Pooled efficacy results indicated that codeine added to paracetamol provided a 5% increase in analgesia on the sum pain intensity difference. This effect was comparable to the difference in analgesic effect between codeine and placebo. The cumulative incidence of side effects with each treatment was comparable in the single dose trials. In the multidose studies a significantly higher proportion of side effects occurred with paracetamol-codeine preparations. CONCLUSION: The difference is analgesic effect between paracetamol-codeine combinations and paracetamol alone was small but statistically significant. In the multidose studies the proportion of patients reporting a side effect was significantly higher with paracetamol-codeine combinations. For occasional pain relief a paracetamol-codeine combination might be appropriate but repeated use increases the occurrence of side effects.
Acetaminophen↗
Role of the Shouldice technique in inguinal hernia repair: a systematic review of controlled trials and a meta-analysis.
The Shouldice technique for inguinal hernia repair has been suggested by some authors as the best conventional method against which other methods using prostheses should be compared. The paper which follows is a systematic review involving a comprehensive search of the medical literature to identify all clinical trials (article or abstract) evaluating the Shouldice repair. After assessment of certain quality criteria, the best studies were pooled in a meta-analysis. Nine publications were found with 11 study arms. In ten studies the results of the Shouldice technique were better than the results of the control arm. Six studies could be pooled in a meta-analysis of 2500 patients; Shouldice was significantly better than control methods (relative risk 0.62 (95 per cent confidence interval 0.45-0.85)). In spite of possible bias caused by different variables (modifications in operative technique, suture material, level of surgeon, follow-up methods and outcome measurement), the results of this systematic review suggest that the Shouldice method is the best current conventional technique for inguinal hernia repair.
Controlled Clinical Trials as Topic↗
Increasing incidence of aneurysms of the abdominal aorta in The Netherlands.
OBJECTIVES: To study the trend in incidence of aneurysms of the abdominal aorta in The Netherlands during the past two decades. SETTING: The Dutch population from 1972 to 1992. DESIGN: Analysis of all hospital admissions and deaths due to aneurysms of the abdominal aorta. OUTCOME MEASURES: Age adjusted and age specific mortality and discharge rates. In-hospital mortality after surgery upon aneurysms of the abdominal aorta. RESULTS: From 1972 to 1992 age adjusted mortality from aneurysms of the abdominal aorta rose from 3.1 to 8.1 per 100,000 in men, and from 1.4 to 2.2 in women. Age adjusted discharge rates (alive and dead) for non-ruptured abdominal aortic aneurysms increased from 3.7 to 37.6 per 100,000 in men and from 1.2 to 5.5 in women. For ruptured aneurysms, the age adjusted discharge rates increased from 2.4 to 10.3 per 100,000 in men and from 0.7 to 1.7 in women. Age adjusted in-hospital mortality after surgery upon non-ruptured aneurysms was halved from 13% in 1972 to 7% in 1992, mortality after acute repair upon ruptured aneurysms also decreased from 52% in 1972 to 36% in 1992. CONCLUSIONS: There was an impressive increase in the hospital based incidence for aneurysms of the abdominal aorta during the past two decades in The Netherlands. An improved detection rate through ultrasound is probably a major contributor to this increase, but gender differences and the rise in the number of ruptured aneurysms suggest that a real increase in incidence may exist, especially in men. Surgical outcome for both ruptured and non-ruptured aneurysms of the abdominal aorta improved.
Age Distribution↗
Steroid injections for shoulder disorders: a systematic review of randomized clinical trials.
BACKGROUND: Patients with shoulder disorders are believed to benefit considerably from steroid injections. However, the controversy about their efficacy persists. AIM: The study was designed to assess the efficacy of steroid injections for shoulder disorders. METHOD: A systematic computerized literature search in Medline (Index Medicus 1/1966-10/1995) and Embase (Excerpta Medica 1/1984-10/1995) was conducted, supplemented with citation tracking of all relevant publications. Studies published before November 1995 were selected if steroid injections were randomly allocated to patients with shoulder disorders and when clinically relevant outcome measures were reported. Because the validity of study outcomes depends heavily on the strength of methodological quality, the methods were assessed systematically by two 'blinded' independent reviewers. This resulted in a method score (maximum 100 points) that was based on four categories: study population, interventions, measurement of effect, and data presentation and analysis. Confidence intervals for the differences between groups in success rates were calculated in order to summarize the efficacy of steroid injections. RESULTS: Only three out of the 16 studies scored more than 50 points, indicating a generally poor quality of methods. Most studies reported small sample sizes. The flaws most often found were incomparability of co-interventions and poor blinding of therapist. The methods assessment was frequently hampered by incomplete information about randomization, prognostic comparability, compliance, outcome measures included, blinding of patients and blinding of outcome measurement. CONCLUSIONS: The evidence in favour of the efficacy of steroid injections for shoulder disorders is scarce. The methods of most studies appear to be of poor quality. The few studies that appear to be credible do not provide conclusive evidence about which patients at what time in the course of shoulder disorders benefit most from steroid injections.
Humans↗
[The Cochrane Collaboration; systematic reviews of knowledge from randomized studies].
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Diffusion of Innovation↗
Trials in palliative care.
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Colorectal Neoplasms↗
Hyperbaric oxygen for multiple sclerosis. Review of controlled trials.
This review assesses the evidence of the efficacy of hyperbaric oxygen in multiple sclerosis. Material & methods - We used a list of predefined criteria for good methodology and interpreted the results of 14 identified controlled trials with emphasis on the quality. Results - At least eight trials can be considered to have a reasonable to high quality. In one of these 8 trials the results were in favour of hyperbaric oxygen treatment; the others found no clear positive effects. The patients had chronic progressive or chronic stable multiple sclerosis. In most trials, hyperbaric oxygen was supplied at pressures of 1.75-2 ATA, during 20 sessions of 90 min in 4 weeks. The principle endpoint was the (Expanded) Disability Status Score [(E)DSS] and the Functional Status Score as described by Kurtzke. Also specific outcomes such as evoked potentials were frequently used, but no consistent positive effects were demonstrated. Side effects were generally minor, ear and visual problems predominated. Conclusions - The majority of controlled trials could not show positive effects. Further evidence might consist of trials in patients with disease of recent onset or with other dosing regimens but the case for such further trials is not strong. Considering the state of affairs we cannot recommend the use of hyperbaric oxygen in the treatment of multiple sclerosis.
Activities of Daily Living↗
Placebo effect in double-blind clinical trials: a review of interactions with medications.
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Double-Blind Method↗
Evening primrose oil.
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Arthritis, Rheumatoid↗
The comprehensiveness of Medline and Embase computer searches. Searches for controlled trials of homoeopathy, ascorbic acid for common cold and ginkgo biloba for cerebral insufficiency and intermittent claudication.
OBJECTIVE: To assess the comprehensiveness of Medline and Embase computer searches for controlled trials. DESIGN: Comparison of articles found after an exhaustive search of the literature with the yield of a Medline or Embase search. This was performed for controlled clinical trials on the efficacy of three interventions: homoeopathy, ascorbic acid for common cold, and ginkgo biloba for intermittent claudication and cerebral insufficiency. The number of controlled trials found by exhaustive search of the literature was 107, 61 and 45, respectively. RESULTS: For homoeopathy, ascorbic acid and ginkgo the proportion of all trials found by Medline was 17%, 36% and 31% respectively and for Embase 13%, 25% and 58% respectively. After checking of the references in the Medline articles 44%, 79% and 76% of all trials were identified. After checking of the references in the Embase articles 42%, 72% and 93% of all trials were identified. About 20% of the articles was not correctly indexed. Of the best trials 68%, 91% and 83% could be found with Medline and 55%, 82% and 92% of the best trials were identified through Embase. CONCLUSIONS: For the topics mentioned, Medline and Embase searches are sufficient to get an impression of the evidence from controlled trials, but only if references in the articles are followed for further evidence. If one wants to get a more complete picture, additional search strategies make sense. Of course, this picture may be different for other topics.
Abstracting and Indexing↗
Ginkgo biloba for cerebral insufficiency.
1. By means of a critical review we tried to establish whether there is evidence from controlled trials in humans on the efficacy of Ginkgo biloba extracts in cerebral insufficiency. 2. The methodological quality of 40 trials on Ginkgo and cerebral insufficiency was assessed using a list of predefined criteria of good methodology, and the outcome of the trials was interpreted in relation to their quality. A comparison of the quality was made with trials of co-dergocrine, which is registered for the same indication. 3. There were eight well performed trials out of a total of 40. Shortcomings were limited numbers of patients included, and incomplete description of randomization procedures, patient characteristics, effect measurement and data presentation. In no trial was double-blindness checked. Virtually all trials reported positive results, in most trials the dosage was 120 mg Ginkgo extract a day, given for at least 4-6 weeks. For the best trials, there were no marked differences in the quality of the evidence of the efficacy of Ginkgo in cerebral insufficiency compared with co-dergocrine. The results of the review may be complicated by a combination of publication bias and other biases, because there were no negative results reported in many trials of low methodological quality. 4. Positive results have been reported for Ginkgo biloba extracts in the treatment of cerebral insufficiency. The clinical evidence is similar to that of a registered product which is prescribed for the same indication. However, further studies should be conducted for a more detailed assessment of the efficacy.
Cerebrovascular Disorders↗
Review articles and publication bias.
Publication bias occurs if the results from studies which have not been published are different from the published ones. From a Bayesian viewpoint, it also concerns non-publication of studies with similar results as the published ones because the strength of the evidence will be influenced. Publication bias complicates the interpretation of reviews and meta-analyses. If favourable results are published more often there will be an overestimation of the effects of a treatment. There have been several attempts to assess the magnitude of publication bias. Unpublished trials could be identified by means of a survey among researchers, and the results could subsequently be compared with the outcomes of published trials. Also, the results from published trials could be compared with trials from a registry. Furthermore, the results from registered but unpublished trials could be compared with those of registered and subsequently published trials. Studies addressing publication bias have shown that it is a serious problem which complicates the interpretation of reviews. In assessments of publication bias other factors must be taken into account. These include the mode of publication: refereed journals, other journals, books, etc. Differences could also be related to the quality of trials. Finally, the source of funding may influence both the results and subsequent publication. Publication bias can only be avoided by registration of all trials before data collection is started; several of such registries have already been installed. Perhaps, if more of such registries exist, reviewers could only use registered trials for their main conclusions. All other information could then be considered sensitive to publication bias.
Meta-Analysis as Topic↗
Niacin and vitamin B6 in mental functioning: a review of controlled trials in humans.
Fifty-three controlled trials of the effects of niacin, vitamin B6, and multivitamins on mental functions are reviewed. The results are interpreted with emphasis on the methodological quality of the trials. It turns out that virtually all trials show serious short-comings: in the number of participants, the presentation of baseline characteristics and outcomes, and the description of changes in concomitant treatments. Only in autistic children are some positive results are found with very high dosages of vitamin B6 combined with magnesium, but further evidence is needed before more definitive conclusions can be drawn. For many other indications (hyperactive children, children with Down's syndrome, IQ changes in healthy schoolchildren, schizophrenia, psychological functions in healthy adults and geriatric patients) there is no adequate support from controlled trials in favor of vitamin supplementation.
Adult↗
Trials of homeopathy.
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Clinical Trials as Topic↗
Clinical trials of homoeopathy.
OBJECTIVE: To establish whether there is evidence of the efficacy of homoeopathy from controlled trials in humans. DESIGN: Criteria based meta-analysis. Assessment of the methodological quality of 107 controlled trials in 96 published reports found after an extensive search. Trials were scored using a list of predefined criteria of good methodology, and the outcome of the trials was interpreted in relation to their quality. SETTING: Controlled trials published world wide. MAIN OUTCOME MEASURES: Results of the trials with the best methodological quality. Trials of classical homoeopathy and several modern varieties were considered separately. RESULTS: In 14 trials some form of classical homoeopathy was tested and in 58 trials the same single homoeopathic treatment was given to patients with comparable conventional diagnosis. Combinations of several homoeopathic treatments were tested in 26 trials; isopathy was tested in nine trials. Most trials seemed to be of very low quality, but there were many exceptions. The results showed a positive trend regardless of the quality of the trial or the variety of homeopathy used. Overall, of the 105 trials with interpretable results, 81 trials indicated positive results whereas in 24 trials no positive effects of homoeopathy were found. The results of the review may be complicated by publication bias, especially in such a controversial subject as homoeopathy. CONCLUSIONS: At the moment the evidence of clinical trials is positive but not sufficient to draw definitive conclusions because most trials are of low methodological quality and because of the unknown role of publication bias. This indicates that there is a legitimate case for further evaluation of homoeopathy, but only by means of well performed trials.
Clinical Trials as Topic↗