Infertility treatment: from cookery to science. The epidemiology of randomised controlled trials

Abstract

Objectives To review the epidemiology of published randomised controlled trials in infertility treatment over the last 25 years, with special emphasis on the number and quality of trials. Design Computer literature review by MEDLINE backed up by a manual search of 41 journals. Each trial was classified according to the methodology described and quality criteria. The results were recorded in a computer database. Odds ratios (OR) and confidence intervals (CI) were calculated where the data were sufficient. Subjects Couples suffering from primary or secondary infertility. The trials studied 33 761 patients overall. Setting Institute of Epidemiology and Health Services Research, Leeds. Results Five hundred and one randomised trials in male and female infertility treatment were identified between 1966 and 1990. Pregnancy was an outcome in 291 (58%) and these were the subject of detailed analysis. Two hundred and twenty‐four (77%) and 67 (23%) ‘pregnancy trials’ were concerned, respectively, with female and male infertility. Four per cent of the trials were preceded by a sample size calculation, and the average sample size was 96 patients (range 5–933); 700 patients per group would be required to demonstrate plausible success rates for most treatments. The method of randomisation was unstated or pseudo‐randomised in 206 (71%) of trials where pregnancy was an outcome. Only 29 (5.8%) of studies were multicentre. The method of confirmation of pregnancy was omitted for 70% of papers. Cross‐over design was used in 103 (21%) of cases. Meta‐analysis is possible for selected topics such as the use of anti‐oestrogens in idiopathic oligospermia and unexplained female infertility. Eight cases of double reporting were identified. Conclusions Trials using randomised methodology were relatively few in comparison with other branches of medicine, although their use is important in the evaluation of treatment for infertility as treatment‐independent pregnancy is common. It was encouraging to note that an exponential increase in the use of this methodology occurred during the last three years, especially in association with assisted conception techniques, and meta‐analysis has become possible for selected topics. However, many trials suffer from an unrealistically small sample size, inappropriate use of cross‐over design or pseudo‐randomisation. The trend towards properly controlled studies should be encouraged but these studies should be of improved quality and organised on a multicentre or even international basis.

Dissemination and publication of research findings: an updated review of related biases

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“…22 Vandekerckhove et al (1993) identified a review of RCTs of infertility treatment and found that 'six studies with a significant result (but none with a non-significant result) were reported in four publications from the same institution'. 177 The updating identified only an abstract by Martin et al (2004) in which they examined the impact of including duplicate publications in a metaanalysis of off-pump versus on-pump coronary artery bypass surgery.…”

Schizophrenia trials: past, present and future

“…The creation of registers of randomised controlled trials to assist the preparation and maintenance of systematic reviews affords an opportunity to assess the quality and content of evaluative research within welldefined sampling frames (Adams & Gelder, 1994) When this large survey was planned there were examples of surveys of randomised trials within specific journals (Ahmed et al, 1998;Lent & Langenbach, 1996;Fahey et al, 1995;Doll, 1998) but research into the quality and content of trials within specific health care specialities was, and is, less common (Chalmers, 1986;Vandekerckhove et al, 1993;Silagy, 1993;Chalmers et al, 1986;Nicolucci et al, 1989;Cheng et al, 2000).checked for duplicates before two trained selectors highlighted studies that were clearly or possibly relevant. Full copies of these reports were then acquired (6000), re-inspected and, if meeting the inclusion criteria, added to the final register.…”

“…(Vandekerckhove et al, 1993). Instead, observational data (often from large, insurance claims databases) have been used in 'outcomes research'.…”

Les traitements médicaux de l’oligoasthénozoospermie idiopathique

“…Trois 6tudes comparant les r6sultats avec ceux obtenus avec un placebo montrent que ce traitement est inefficace dans ces conditions (Tableau 1). Dans la m6ta-analyse r6alis6e par Vandekerkhove et al [56] ou O'Donovan et al [36], les r4sultats combin6s montrent l'absence de diff6rence entre les patients trait6s et ceux ayant r%u un placebo, en terme de grossesses obtenues.…”