Margaret Haugh

Evidence of clinical efficacy of homeopathy

AbstractObjective: To establish, using a systematic review and meta-analysis, whether there is any evidence from randomised controlled clinical trials of the efficacy of homeopathic treatment in patients with any disease. Data sources: Published and unpublished reports of controlled clinical trials available up to June 1998, identified by searching bibliographic databases (Medline, Embase, Biosis, PsychInfo, Cinahl, British Library Stock Alert Service, SIGLE, Amed), references lists of selected papers, hand searching homeopathic journals and conference abstracts, and contacting pharmaceutical companies. Trials selection: Trials were selected using an unblinded process by two reviewers. The selection criteria were randomised, controlled trials in which the efficacy of homeopathic treatment was assessed relative to placebo in patients using clinical or surrogate endpoints. Prevention trials or those evaluating only biological effects were excluded. One hundred and eighteen randomised trials were identified and evaluated for inclusion. Sixteen trials, representing 17 comparisons and including a total of 2617 evaluated patients, fulfilled the inclusion criteria. Data extraction: Data were extracted by two reviewers independently, using a summary form. Disagreements were resolved by a third person. Data synthesis: The evidence was synthesised by combining the significance levels (P values) for the primary outcomes from the individual trials. The combined P value for the 17 comparisons was highly significant P=0.000036. However, sensitivity analysis showed that the P value tended towards a non-significant value (P=0.08) as trials were excluded in a stepwise manner based on their level of quality. Conclusions: There is some evidence that homeopathic treatments are more effective than placebo; however, the strength of this evidence is low because of the low methodological quality of the trials. Studies of high methodological quality were more likely to be negative than the lower quality studies. Further high quality studies are needed to confirm these results.

Surrogate endpoints: A basis for a rational approach

SummaryIn clinical trials, the clinical endpoint is often replaced by an intermediate endpoint, known in some instances as a “surrogate” endpoint. The reasons for the substitution are often both practical and financial. At present, no theoretical basis or practical guidelines exist to help in the choice of surrogate endpoints.An approach is proposed here, based on three provisos which can be verified using one of a series of equations, if sufficient data on the pathophysiology and epidemiology of the disease are available. It is shown that even a strong statistical correlation is not a sufficient criterion for the definition of a surrogate endpoint.It is apparent that results obtained with the commonly used “surrogate” endpoints should be cautiously considered and that the assessment of treatments should, when possible, be based on clinical rather than intermediate endpoints.

EasyMA: a program for the meta-analysis of clinical trials.

Meta-analysis of clinical trial data is an increasingly important method in clinical research, particularly in the field of therapeutic evaluation. This method uses some specific statistical techniques which are not all available on standard packages and therefore require specific developments. This paper describes a program designed to help medical researchers perform meta-analyses of clinical trial data with dichotomous outcomes. This program includes the various statistical methods of meta-analysis and enables cumulative meta-analysis and sub-groups to be performed. A robustness index can be determined and the results obtained in table and graphic formats. Data-editing and data-manipulating facilities are also possible. Much care has been taken to make the user interface as user-friendly as possible, so that the program is within the reach of all medical researchers.

Cytomegalovirus prophylaxis with antiviral agents in solid organ transplantation : a meta-analysis.

BACKGROUND The aim of this meta-analysis was to assess the efficacy of antiviral agents to prevent, in solid organ transplant recipients, cytomegalovirus infection and symptomatic disease and to decrease the incidence of acute rejection, graft loss, and death. METHODS Of the studies identified, 13 met the following inclusion criteria: prospective randomized study, in adults or pediatric recipients of a solid organ transplant, where one group in the study received a prophylactic treatment with acyclovir and/or ganciclovir begun before the cytomegalovirus infection and a control group was not treated or receive placebo. RESULTS Prophylactic treatment was found to be associated with a significant decrease of cytomegalovirus disease compared with placebo or no treatment, using the logarithm of relative risk method (relative risk=0.50; 95% confidence interval, 0.40-0.62; P-value for chi-square association <0.001). Prophylactic treatment decreased also the rate of cytomegalovirus infection (relative risk=0.74; 95% confidence interval, 0.62-0.88; P<0.001). Our analysis failed to show a significant decrease of graft loss, acute rejection, and death in the prophylactic treatment group. Subgroup analysis based on the type of antiviral agent (acyclovir or ganciclovir) and on the type of organ (kidney or liver) gave comparable results. CONCLUSION The use of antiviral agents for the prevention of cytomegalovirus disease and cytomegalovirus infection in solid organ transplantation is supported by this meta-analysis.

Ramipril-Induced Regression of Left Ventricular Hypertrophy in Treated Hypertensive Individuals

The objective of this trial was to assess the effects of 6-month daily treatment with two doses of ramipril on left ventricular mass and the dependence of this on blood pressure changes in hypertensive patients with left ventricular hypertrophy. After a selection phase of 4 to 6 weeks with patients under antihypertensive therapy with 20 mg furosemide daily, 115 patients with either controlled or uncontrolled hypertension and left ventricular hypertrophy were randomized in a double-blind manner to receive either placebo (n = 40), 1.25 mg (low dose, n = 38), or 5 mg (regular dose, n = 37) ramipril daily for 6 months. Treatment with furosemide was continued unchanged during this phase. The main outcome measured was left ventricular hypertrophy regression as assessed from central blind reading of echocardiograms recorded at randomization and after 6 months. No significant differences were observed for changes in casual or ambulatory blood pressure between the three groups. Left ventricular mass index was found to be significantly reduced in patients receiving 5 mg ramipril compared with those receiving placebo (-10.8 +/- 3.7 versus +4.1 +/- 4.0 g/m2, P = .008); in patients receiving 1.25 mg ramipril, the difference was close to borderline significance compared with placebo (-7.0 +/- 4.3 g/m2, P = .06). Similar results were observed for changes in left ventricular mass (-20.3 +/- 6.6 and -13.0 +/- 7.8 g in the 5- and 1.25-mg ramipril groups, respectively, versus +9.1 +/- 7.2 g in the placebo group; P = .004 and .04, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

A randomized comparison of the effect of four antihypertensive monotherapies on the subjective quality of life in previously untreated asymptomatic patients: field trial in general practice

Objective: To assess the equivalence of four antihypertensive treatments in patients with mild-to-moderate hypertension, and to compare the effects of those drugs on the subjective quality of life and clinical safety. Design, setting and patients: 653 patients aged ≥18 years with untreated hypertension were randomly allocated to receive a combination of two diuretics (altizide and spironolactone), a β -blocker (bisoprolol), a calcium antagonist (verapamil), or an angiotensin converting enzyme (ACE) inhibitor (enalapril). Follow-up lasted for 1 year. Main outcome measures: A composite outcome of the following measures was used to define success: attendance at the 12-month visit; at least nine supine DBP measurements during the study; and median supine DBP<90mmHg and a reduction of at least l0mmHg compared with the baseline value. Failure was defined as one or more of those criteria not being fulfilled. Equivalence was concluded if the 95% confidence interval for the success rates differed between two groups by less than ±10%. Clinical safety and subjective quality of life were also assessed. Results: No statistically significant differences in the change in DBP or systolic blood pressure were observed between the groups. The success rates were 43.9, 42.0, 32.5 and 43.9% in diuretic, β -blocker, calcium antagonist and ACE inhibitor groups, respectively. Equivalence between the treatments could not be concluded, although analysis with a larger equivalence interval showed that some comparisons indicated equivalence. Significant improvement in satisfaction was observed for certain items for subjective quality of life at 1 month in the calcium antagonist treatment group, and significant differences in the responses to the clinical safety questionnaire were observed after 1-month follow-up in calcium antagonist and β-blocker groups. Differences were no longer significant after 9 months. Conclusions: These results do not provide evidence on the basis of efficacy of blood pressure lowering or ability to increase short-term (1-year) safety and quality of life favouring any particular treatment among the studied drugs for newly diagnosed patients with mild-to-moderate hypertension.

Bridging the gap between therapeutic research results and physician prescribing decisions: knowledge transfer, a prerequisite to knowledge translation

Background: A wide gap continues to exist between available therapeutic research results and physician’s prescribing. Numerous explanations account for this gap, but one central reason is the difficulty in transferring comprehensive research information to practicing clinicians. This problem arises from information overload and the growing complexity of research findings. We propose a multistep process that can be used to develop systems to bridge this information/prescription gap. The steps include: comprehensively collecting and summarizing clinical trial reports, scoring and ranking these according to their level of evidence, exploring and synthesizing the data using meta-analyses, summarizing these results, representing them in an easily understandable form, and transmitting the overview findings to prescribers at the time they need them. Discussion: This ambitious endeavor is needed to ensure that prescribers have access to pertinent research results for use in their prescription decisions. We demonstrate in this article that there are no theoretical or technical obstacles to make the proposed system workable.

Towards personalized medicine: exploring the consequences of the effect model-based approach

Although personalized medicine has been a subject of research and debate in recent years, it has been underused in medical practice, except in some cancers. We believe that the main reason for the gap between the potential of personalized medicine and its use in daily medical practice can be explained by the lack of an appropriate tool to facilitate the use of biomarker values in a doctors decision-making process. We propose that the effect model could form the basis of such a tool.

Evaluation of two evidence-based knowledge transfer interventions for physicians. A cluster randomized controlled factorial design trial: the CardioDAS Study

To investigate the potential benefits of two modes of evidence‐based knowledge transfer (‘active’ and ‘passive’ modes) in terms of improvement of intention of prescription, knowledge, and real prescription in practice, we performed an open randomized controlled trial (CardioDAS) using a factorial design (two tested interventions: ‘active’ and ‘passive’ knowledge transfer) and a hierarchical structure (cluster of physicians for each department level). The participants were cardiologists working in French public hospitals. In the ‘passive’ transfer group, cardiologists received evidence‐based knowledge material (available on Internet) every week for a duration of 1 year. In the ‘active’ transfer group, two knowledge brokers (EA, PN) visited the participating departments (every 2 months for 1 year, 2 h per visit). The primary outcome consisted in the adjusted absolute mean variation of score (difference between post‐ and pre‐study session) of answers to simulated cases assessing the intention to prescribe. Secondary outcomes were the variation of answers to a multiple‐choice questionnaire (MCQ) assessing knowledge and of the conformity of real prescriptions to evidence‐based reference assessing the behavioral change. Twenty‐two French units (departments) of cardiology were randomized (72 participating cardiologists). In the ‘active’ transfer group, the primary outcome was more improved than that in the control (P = 0.031 at the department level, absolute mean improvement of 5 points/100). The change in knowledge transfer (MCQ) was also significant (P = 0.039 at the department level, absolute mean improvement of 6 points/100). However, no benefit was shown in terms of prescription conformity to evidence. For the ‘passive’ mode of knowledge transfer and for the three outcomes considered, no improvement was identified. CardioDAS findings confirm that ‘active’ knowledge transfer has some impact on participants’ intent to prescribe and knowledge, but no effect on behavioral outcome. ‘Passive’ transfer seems far less efficient. In addition, the size of the benefit remains small and its consequences limited in practice.

Standardization of terminology in meta‐analysis: a proposal for working definitions

Summary— In this paper we present a brief overview of the growing concern to standardize definitions and terminology in meta‐analysis. This tool has become inescapable in both drug research and therapeutic evaluation. The performed and published meta‐analyses are increasing, as well as the variation in the meaning of the terms used in meta‐analysis. In the second part of the paper we propose glossary of the most common terms used in reports of meta‐analyses. The glossary has been written by only one group of scientists, the definitions are therefore proposed to the scientific community as working definitions, to be subject to reactions from leaders in meta‐analysis.