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At least 1,009 records · Page 56Linked to original sources
PubMed2006

Adjuvant chemotherapy for invasive bladder cancer (individual patient data).

BACKGROUND: Controversy exists as to whether adjuvant chemotherapy improves survival in patients with invasive bladder cancer, despite a number of randomised controlled trials. OBJECTIVES: To evaluate the effect of adjuvant chemotherapy in invasive bladder cancer. We conducted a systematic review and meta-analysis of updated individual patient data from all available randomised controlled trials comparing local treatment plus adjuvant chemotherapy versus the same local treatment alone. SEARCH STRATEGY: MEDLINE and Cancerlit searches were supplemented with information from registers and hand searching meeting proceedings and also by discussion with relevant trialists and organisations. They have been regularly updated until September 2004. SELECTION CRITERIA: Trials that aimed to randomise patients with biopsy proven invasive (i.e. clinical stage T2-T4a) transitional cell carcinoma of the bladder to receive local definitive treatment with or without adjuvant chemotherapy were eligible for inclusion. DATA COLLECTION AND ANALYSIS: We collected, validated and re-analysed updated data on all randomised patients from all available randomised trials, including 491 patients from 6 RCTs. For all outcomes, we obtained overall pooled hazard ratios using the fixed effects model. To explore the potential impact of trial design, we pre-planned analyses that grouped trials by important aspects of their design that might influence the treatment effect. To investigate any differences in effect by pre-defined patient sub-groups, we used a stratified logrank analysis on the primary endpoint of survival. MAIN RESULTS: Analyses were based on 491 patients from six trials, representing 90% of all patients randomised in cisplatin-based combination chemotherapy trials and 66% of patients from all eligible trials. The power of this meta-analysis is clearly limited. The overall hazard ratio for survival of 0.75 (95%CI 0.60-0.96, p=0.019) suggests a 25% relative reduction in the risk of death for chemotherapy compared to that on control. Cox regression suggests that small imbalances in patient characteristics do not bias the results in favour of chemotherapy. However, the impact of trials that stopped early, of patients not receiving allocated treatments or not receiving salvage chemotherapy is less clear. AUTHORS' CONCLUSIONS: This IPD meta-analysis provides the best evidence currently available on the role of adjuvant chemotherapy for invasive bladder cancer. However, at present there is insufficient evidence on which to reliably base treatment decisions. These results highlight the urgent need for further research into the use of adjuvant chemotherapy. The results of appropriately sized randomised trials, such as the ongoing EORTC-30994 trial are needed before any definitive conclusions can be drawn.

Chemotherapy, Adjuvant↗
PubMed2003

Investing in new technology: the PET experience.

As funding available to health services is limited, demonstrating the cost effectiveness of new technologies is an important step in their introduction. This is especially challenging for diagnostic technologies, for which the usual paradigm of reliance on well-designed, randomised controlled trials may not be appropriate. A recently completed Health Technology Assessment of fluorine-18 deoxyglucose (FDG)-positron emission tomography (PET) imaging in cancer management, focused on addressing whether the introduction of PET imaging would be beneficial to patients in the NHS in Scotland, exemplifies some of the challenges. Although a substantial body of published literature exists for this technology, most of the studies report diagnostic accuracy rather than improved patient outcomes. Direct evidence that such improvement occurs, and is sufficient to meet the NHS' criteria for cost effectiveness, from well-designed trials would constitute the most immediately persuasive case for the introduction of PET imaging. In the absence of such evidence, collaboration is required between a variety of disciplines to synthesise evidence from a variety of sources to create informative decision models that estimate long-term patient outcomes. The use of such decision models enabled the Health Technology Board for Scotland (now a part of NHS Quality Improvement Scotland) to determine that FDG-PET imaging is likely to be cost effective in selected applications and identified long-term patient benefits that it would not be possible to study in a randomised controlled trial.

Cost-Benefit Analysis↗
PubMed1997

Systematic review of randomised controlled trials of strategies to promote adherence to tuberculosis treatment.

OBJECTIVE: To determine the effectiveness of strategies to promote adherence to treatment for tuberculosis. IDENTIFICATION: Searches in Medline (1966 to August 1996), the Cochrane trials register (up to October 1996), and LILACS (Literatura Latinoamericana y del Caribe en Ciencias de la Salud) (1982 to September 1996); screening of references in articles on compliance and adherence; contact with experts in research on tuberculosis and adherence. INCLUSION CRITERIA: Randomised or pseudorandomised controlled trials of interventions to promote adherence with curative or preventive treatment for tuberculosis, with at least one measure of adherence. MAIN OUTCOME MEASURE: Relative risks and 95% confidence intervals for estimates of effect for categorical outcomes. RESULTS: Five trials met the inclusion criteria. The relative risk for tested reminder cards sent to patients who defaulted on treatment was 1.2 (95% confidence interval 1.1 to 1.4), for help given to patients by lay health workers 1.4 (1.1 to 1.8), for monetary incentives offered to patients 1.6 (1.3 to 2.0), for health education 1.2 (1.1 to 1.4), for a combination of a patient incentive and health education 2.4 (1.5 to 3.7) or 1.1 (1.0 to 1.2), and for intensive supervision of staff in tuberculosis clinics 1.2 (1.1 to 1.3). There were no completed trials of directly observed treatment. All of the interventions tested improved adherence. On current evidence it is unclear whether health education by itself leads to better adherence to treatment. CONCLUSIONS: Reliable evidence is available to show some specific strategies improve adherence to tuberculosis treatment, and these should be adopted in health systems, depending on their appropriateness to practice circumstances. Further innovations require testing to help find specific approaches that will be useful in low income countries. Randomised controlled trials evaluating the independent effects of directly observed treatment are awaited.

Attitude to Health↗
PubMed2003

Systematic review of effect of coenzyme Q10 in physical exercise, hypertension and heart failure.

COENZYME Q10 IN PHYSICAL EXERCISE. We identified eleven studies in which CoQ10 was tested for an effect on exercise capacity, six showed a modest improvement in exercise capacity with CoQ10 supplementation but five showed no effect. CoQ10 IN HYPERTENSION. We identified eight published trials of CoQ10 in hypertension. Altogether in the eight studies the mean decrease in systolic blood pressure was 16 mm Hg and in diastolic blood pressure, 10 mm Hg. Being devoid of significant side effects CoQ10 may have a role as an adjunct or alternative to conventional agents in the treatment of hypertension. CoQ10 IN HEART FAILURE. We performed a randomised double blind placebo-controlled pilot trial of CoQ10 therapy in 35 patients with heart failure. Over 3 months, in the CoQ10 patients but not in the placebo patients there were significant improvements in symptom class and a trend towards improvements in exercise time. META-ANALYSIS OF RANDOMISED TRIALS OF COENZYME Q10 IN HEART FAILURE. In nine randomised trials of CoQ10 in heart failure published up to 2003 there were non-significant trends towards increased ejection fraction and reduced mortality. There were insufficient numbers of patients for meaningful results. To make more definitive conclusions regarding the effect of CoQ10 in cardiac failure we recommend a prospective, randomised trial with 200-300 patients per study group. Further trials of CoQ10 in physical exercise and in hypertension are recommended.

Cardiac Output, Low↗
PubMed2005

Painful bladder syndrome/interstitial cystitis.

Painful bladder syndrome (PBS) is the term used to refer to a chronic symptom complex of urinary frequency and bladder 'pressure', discomfort or pain in the absence of any other reasonable cause for these symptoms (such as infection). Interstitial cystitis (IC) is the established term used by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) consensus workshop for which a research definition was formulated in the late 1980s. Opinion varies regarding not only definition but also the usefulness of diagnostic investigations such as urodynamic assessment and the potassium sensitivity test. There are still controversies concerning the most basic investigation of cystoscopy in PBS/IC. New developments in the study of PBS/IC include the identification of a potential urinary biomarker, antiproliferative factor (APF), which is produced by urothelial cells in IC and thought to inhibit proliferation. In addition, condition-specific validated questionnaires should aid evaluation, and a growing number of randomised controlled trials should enable clinicians to use evidence-based therapeutic options.

Administration, Intravesical↗
PubMed2002

Unequal group sizes in randomised trials: guarding against guessing.

We cringe at the pervasive notion that a randomised trial needs to yield equal sample sizes in the comparison groups. Unfortunately, that conceptual misunderstanding can lead to bias by investigators who force equality, especially if by non-scientific means. In simple, unrestricted, randomised trials (analogous to repeated coin-tossing), the sizes of groups should indicate random variation. In other words, some discrepancy between the numbers in the comparison groups would be expected. The appeal of equal group sizes in a simple randomised controlled trial is cosmetic, not scientific. Moreover, other randomisation schemes, termed restricted randomisation, force equality by departing from simple randomisation. Forcing equal group sizes, however, potentially harms the unpredictability of treatment assignments, especially when using permuted-block randomisation in non-double-blinded trials. Diminished unpredictability can allow bias to creep into a trial. Overall, investigators underuse simple randomisation and overuse fixed-block randomisation. For non-double-blinded trials larger than 200 participants, investigators should use simple randomisation more often and accept moderate disparities in group sizes. Such unpredictability reflects the essence of randomness. We endorse the generation of mildly unequal group sizes and encourage an appreciation of such inequalities. For non-double-blinded randomised controlled trials with a sample size of less than 200 overall or within any principal stratum or subgroup, urn randomisation enhances unpredictability compared with blocking. A simpler alternative, our mixed randomisation approach, attains unpredictability within the context of the currently understood simple randomisation and permuted-block methods. Simple randomisation contributes the unpredictability whereas permuted-block randomisation contributes the balance, but avoids the perfect balance that can result in selection bias.

Bias↗
PubMed2002

[The use of randomisation in clinical studies in rehabilitation medicine: basics and practical aspects].

New therapies in rehabilitation medicine have to be evaluated with clinical trials. For drug approval the methodology of clinical trials is standardized world wide and the results of these studies are widely accepted. This standard should be achieved in clinical trials in rehabilitation research, too. One of the standards is the existence of a control group, comparing the effect of the new intervention against controls. In addition, the investigational and control groups must be equal in terms of the structure of possible confounders. Randomisation is the best possibility to distribute the patients to the therapy-groups, confounders will be equally distributed by chance. Other procedures for assignment to the study groups can result in confounding and lead into biased results. In spite of these advantages, randomisation is not generally accepted in rehabilitation research up to now. There are some reservations, mostly ethical, organisational and methodological ones. However, randomised clinical trials should be conducted in rehabilitation research in order to obtain more convincing results. Our intention is to bring some input in this debate and to present basics and practical aspects of randomisation.

Bias↗
PubMed1996

What proportion of primary psychiatric interventions are based on evidence from randomised controlled trials?

OBJECTIVES: To estimate the proportion of psychiatric inpatients receiving primary interventions based on randomised controlled trials or systematic reviews of randomised controlled trials. DESIGN: Retrospective survey. SETTING: Acute adult general psychiatric ward. SUBJECTS: All patients admitted to the ward during a 28 day period. MAIN OUTCOME MEASURES: Primary interventions were classified according to whether or not they were supported by evidence from randomised controlled trials or systematic reviews. RESULTS: The primary interventions received by 26/40 (65%; 95% confidence interval (95% CI) 51% to 79%) of patients admitted during the period were based on randomised trials or systematic reviews. CONCLUSIONS: When patients were used as the denominator, most primary interventions given in acute general psychiatry were based on experimental evidence. The evidence was difficult to locate; there is an urgent need for systematic reviews of randomised controlled trials in this area.

Adult↗
PubMedDate not supplied

Mega-trials: methodological issues and clinical implications.

A recent development of the therapeutic trial has been the mega-trial: a large, simple randomised trial analysed on an 'intention to treat' basis. Mega-trials have advantages in terms of increased statistical power, but also raise several new questions of interpretation. In mega-trials, randomisation serves to achieve identical allocation groups in a situation where there is poor experimental control and a large measure of between-subject variation. The results of mega-trials cannot readily be generalised because their conclusions are observations, not casual hypotheses, and are therefore not testable. In this sense, mega-trials can be repeated but cannot be replicated. Basic science and clinical science both seek understanding at the level of the individual subject; but in a mega-trial, analysis is only meaningful at the group level. The non-scientific nature of mega-trials derives from their methodology, which dispenses with the scientific aim of maximum experimental control to remove or minimise bias, and instead uses randomisation to achieve an equal distribution of bias between groups.

Bias↗
PubMed1999

Preparation for a pneumococcal vaccine trial in The Gambia: individual or community randomisation?

In preparation for a large phase-3 trial of pneumococcal polysaccharide/conjugate vaccine among infants in The Gambia, the relative merits of community and individual randomisation were considered. The impact of vaccination might be enhanced in a community randomised trial if there was a substantial 'herd' effect. This might occur if those vaccinated comprise a substantial proportion of potential transmitters of infection. However, there are few data on the sources of pneumococcal infections in The Gambia and with the high degree of mobility of people in The Gambia, it seems unlikely that any herd effect would be strong. In the absence of a herd effect, a community-randomised trial would have lower power for the mortality end-points compared to an individually randomised trial of the same size. In addition, a community-randomised trial might not provide sufficient control against potential confounders and blinding might be difficult to sustain if the vaccine has a strong effect. An individually randomised trial seems a better strategy under the conditions prevailing in The Gambia.

Bacterial Vaccines↗
PubMed1980

The scientific and ethical basis of the clinical evaluation of medicines. Report of an international conference, held as a guest conference at the Ditchley Foundations, Ditchley Park, England, 13-16 September 1979.

The scientific basis of the clinical evaluation of medicines is well established, and clinical investigators have also given considerable attention to the ethical problems. But of recent years there has been increasing concern with and criticism of the ethics of these procedures. Lawyers, medical doctors and others have expressed the opinion that the randomised controlled therapeutic trial subordinates the rights of the individual to the advantage of society to a degree that can even be "criminal". Clinical investigators must respond to such criticism, even if it stems only from a few individuals. Therefore, a conference was convened on this topic. The scientific basis of evaluation of medicines in man was reviewed and found to be in accord with the best ethical standards. The objections that have been advanced were considered and were found to be both misconceived and liable to lead to the proliferation of medicines inadequately evaluated for efficacy and safety, to the disadvantage of society.

Clinical Trials as Topic↗
PubMedDate not supplied

The calcium channel blocker debate.

What, finally can we conclude from the work to date regarding the use of CCB's? The large clinical trials here give a number of clear messages to the prescriber. Short-acting dihydropyridine CCB's are unproven as prophylactic agents in ischaemic heart disease. In patients with poor left ventricular function post-infarct, CCB's are associated with an unchanged or increased mortality. Use of medications in the treatment of hypertension should be with proven first-line therapeutic agents; beta-blockers, diuretics; and the long-acting dihydropyridine CCB's nifedipine GITS and nitrendipine. The final argument in the discussion over the safety or otherwise of calcium channel blockers will rest in the completion in the future of a number of prospective, randomised, place-controlled clinical drug trials. These trials are currently ongoing, and their results may not be available until after the year 2000.

Calcium Channel Blockers↗