Random allocation in clinical trials.
Explore the source record for details and available documents.
Anti-Bacterial Agents↗
SEARCH · Search PubMed
Results for “Random Allocation”
Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
Concealed random allocation protects against bias in clinical trials
Explore the source record for details and available documents.
Journal Article↗
Reporting methodology protocols in three acute care journals.
Our study compared the reporting of methodology protocol details in three acute care journals, Annals of Emergency Medicine, Critical Care Medicine, and Journal of Trauma. Eleven criteria previously reported for evaluation of clinical trials in the medical literature were used. These were eligibility criteria, admission before allocation, random allocation, method of randomization, patients' blindness to treatment, blind assessment of outcome, treatment complications, loss to follow-up, statistical methods, statistical analysis, and power. All prospective, interventional, controlled trials appearing in the journals from January 1980 to June 1983 were identified. A total of 45 trials was found. Each study was read independently by two reviewers to determine whether each of the 11 criteria was reported clearly, reported unclearly, or not applicable. Disagreements were resolved by a third reader (adjudicator). The results are reported as the mean proportion of items clearly reported plus or minus the standard deviation: Annals of Emergency Medicine (n = 16), 0.40 +/- 0.18; Journal of Trauma (n = 18), 0.41 +/- 0.24; Critical Care Medicine (n = 11), 0.35 +/- 0.18. A one-way analysis of variance found no statistically significant difference between journals with respect to these proportions (P = .75). The study reveals that these journals, as judged by these criteria, do not report enough methodologic information to allow assessment of bias-reducing techniques and statistical methodology.
Analysis of Variance↗
Comparison of antihypertensive effects of an angiotensin-converting enzyme inhibitor, a calcium antagonist and a diuretic in patients with hypertension not controlled by angiotensin receptor blocker monotherapy.
OBJECTIVE: To compare the additional antihypertensive effects of an angiotensin-converting enzyme inhibitor (ACEI), a dihydropyridine calcium antagonist and a diuretic in patients whose hypertension is not controlled by full-dose angiotensin receptor blocker (ARB) monotherapy. DESIGN AND METHODS: Individuals with an ambulatory blood pressure (ABP) that was not controlled by valsartan 160 mg once daily were allocated randomly to two groups: those in group A (n = 35) were assigned randomly to treatment with benazepril 20 mg once daily or chlorthalidone 12.5 mg once daily, whereas patients in group B (n = 29) were assigned randomly to benazepril 20 mg once daily or amlodipine 5 mg once daily. All individuals continued to receive background valsartan 160 mg once daily. After 5 weeks, patients crossed over to the alternative valsartan-based combination treatment of each group for a second 5-week period. Twenty-four-hour ABP monitoring was performed before the random allocation to groups and at the end of each randomized combination pharmacotherapy period. RESULTS: Sixty-four individuals completed the study: 32 men and 32 women (mean +/- SD age 48.2 +/- 7.9 years, average 24-h ABP on valsartan monotherapy 143.4 +/- 12.6/87.7 +/- 7.8 mmHg). Significant additional antihypertensive effects on the average 24-h ABP were obtained with benazepril (8.6 +/- 8.8/6.3 +/- 6.7 mmHg), amlodipine (15.2 +/- 12.9/9.9 +/- 6.8 mmHg) and chlorthalidone (13.5 +/- 11.6/9.5 +/- 7.7 mmHg) (P < 0.001 for all additional antihypertensive effects). The additional effects of amlodipine and chlorthalidone added to valsartan were approximately 6/3.5 mmHg (P < 0.05) greater than that of benazepril. CONCLUSIONS: In patients in whom hypertension was not controlled by full-dose ARB monotherapy, a diuretic, a calcium antagonist or an ACE inhibitor provided significant additional antihypertensive effect. The antihypertensive effects of the ARB-diuretic and the ARB-calcium antagonist combinations were superior to that of the ARB-ACE inhibitor combination.
Adolescent↗
Properties of simple randomization in clinical trials.
This article presents the properties of complete randomization (e.g., coin toss) and of the random allocation rule (random permutation of n/2 of n elements). The latter is principally used in cases where the total sample size n is known exactly a priori. The likelihood of treatment imbalances is readily computed and is shown to be negligible for large trials (n greater than 200), regardless of whether a stratified randomization is used. It is shown that substantial treatment imbalances are extremely unlikely in large trials, and therefore there is likely to be no substantial effect on power. The large-sample permutational distribution of the family of linear rank tests is presented for complete randomization unconditionally and conditionally, and for the random allocation rule. Asymptotically the three are equivalent to the distribution of these tests under a sampling-based population model. Permutation tests are also presented for a stratified analysis within one or more subgroups of patients defined post hoc on the basis of a covariate. This provides a basis for analysis when some patients' responses are assumed to be missing-at-random. Using the Blackwell-Hodges model, it is shown that complete randomization eliminates the potential for selection bias, but that the random allocation rule yields a substantial potential for selection bias in an unmasked trial. Finally, the Efron model for accidental bias is used to assess the potential for bias in the estimate of treatment effect due to covariate imbalance. Asymptotically, this probability approaches zero for complete randomization and for the random allocation rule. However, for finite n, complete randomization minimizes the probability of accidental bias, whereas this probability is slightly higher with a random allocation rule. It is concluded that complete randomization has merit in large clinical trials.
Clinical Trials as Topic↗
Effect of skin test with M. leprae soluble antigen on reaction to a subsequent test with the same antigen.
Soluble skin-test antigens (STA), produced from armadillo-derived Mycobacterium leprae by Drs. Rees and Convit, were expected to meet the long-felt need of a test for leprosy infection and also to serve as tests for measuring postvaccination sensitization induced by vaccine preparations against leprosy. The present paper reports results from two studies examining the influence, if any, of skin testing with Rees' STA on reaction to a subsequent test with the same antigen. In the first study, 2168 persons from households of leprosy patients and from neighboring households were skin tested with Rees' STA twice at an interval of 6 months. In the second study, 1700 persons, free from leprosy, received either Rees' STA or normal saline by random allocation. A random subset of 850 persons was tested with Rees' STA after 3 months. The remaining 850 persons were tested with Rees' STA after 6 months. In addition, 242 leprosy patients were given Rees' STA or normal saline by random allocation, and all of these patients were tested with Rees' STA after 6 months. The results of the two studies showed that among persons reacting with a small size of reaction to Rees' STA, the size of the reaction to the repeat test was significantly larger. However, from the results of the second study, which included a control group, it was clearly seen that the quantum of boosting or sensitizing effect of the first test as well as that of new sensitization was small over a period of 3-6 months.(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
The unpredictability paradox: review of empirical comparisons of randomised and non-randomised clinical trials.
OBJECTIVE: To summarise comparisons of randomised clinical trials and non-randomised clinical trials, trials with adequately concealed random allocation versus inadequately concealed random allocation, and high quality trials versus low quality trials where the effect of randomisation could not be separated from the effects of other methodological manoeuvres. DESIGN: Systematic review. SELECTION CRITERIA: Cohorts or meta-analyses of clinical trials that included an empirical assessment of the relation between randomisation and estimates of effect. DATA SOURCES: Cochrane Review Methodology Database, Medline, SciSearch, bibliographies, hand searching of journals, personal communication with methodologists, and the reference lists of relevant articles. MAIN OUTCOME MEASURES: Relation between randomisation and estimates of effect. RESULTS: Eleven studies that compared randomised controlled trials with non-randomised controlled trials (eight for evaluations of the same intervention and three across different interventions), two studies that compared trials with adequately concealed random allocation and inadequately concealed random allocation, and five studies that assessed the relation between quality scores and estimates of treatment effects, were identified. Failure to use random allocation and concealment of allocation were associated with relative increases in estimates of effects of 150% or more, relative decreases of up to 90%, inversion of the estimated effect and, in some cases, no difference. On average, failure to use randomisation or adequate concealment of allocation resulted in larger estimates of effect due to a poorer prognosis in non-randomly selected control groups compared with randomly selected control groups. CONCLUSIONS: Failure to use adequately concealed random allocation can distort the apparent effects of care in either direction, causing the effects to seem either larger or smaller than they really are. The size of these distortions can be as large as or larger than the size of the effects that are to be detected.
Clinical Trials as Topic↗
Are pacifiers associated with early weaning from breastfeeding?
BACKGROUND: The pacifier, a non-nutritive sucking device, is commonly used for calming infants. The World Health Organization/United Nation's Children's Fund (WHO/UNICEF) Baby Friendly Hospital Initiative recommends avoiding pacifiers in breastfed term infants because it is thought to lead to early weaning. Most studies that found early weaning to be associated with pacifier use were observational in design. This Critically Appraised Topic evaluates a randomized controlled trial that examines pacifiers and early weaning. PURPOSE: The objectives of the study analyzed were to test whether regular pacifier use has a causal effect on early weaning from the breast by 3 months of age and to assess the difference in results when the data are examined using randomized intervention allocation (intention to treat) versus observational use of pacifiers. METHODS: Two hundred eighty-one breastfeeding women and their healthy term infants were allocated randomly to 1 of 2 counseling interventions. Both groups received basic breastfeeding promotion information. In addition, the experimental group mothers (n = 140) were asked to avoid pacifiers and were given other alternatives for comforting a crying infant. Logs detailing infant crying, fussing, and pacifier use were completed at 4, 6, and 9 weeks of age, and an interview at 3 months determined the duration of breastfeeding. RESULTS: The experimental group had a higher rate of total avoidance of pacifier use (38.6% v 16% in the control group) and less daily use of pacifiers (40.8% v 55.7%). When the data were analyzed based on the intention to treat (randomized allocation), the experimental intervention group had similar rates of early weaning as the control group (18.9% v 18.3%). When the data were analyzed on the treatment given (ignoring randomization), a strong observational association was found between daily exposure to pacifiers and weaning by 3 months (25% v 12.9% of exposed versus unexposed groups). CONCLUSION: The results imply that pacifier use may be a marker of breastfeeding difficulties or decreased maternal motivation to breastfeed, as opposed to being the causal agent in early weaning.
Adult↗
Lay public's understanding of equipoise and randomisation in randomised controlled trials.
OBJECTIVES: To research the lay public's understanding of equipoise and randomisation in randomised controlled trials (RCTs) and to look at why information on this may not be not taken in or remembered, as well as the effects of providing information designed to overcome barriers. DESIGN: Investigations were informed by an update of systematic review on patients' understanding of consent information in clinical trials, and by relevant theory and evidence from experimental psychology. Nine investigations were conducted with nine participants. SETTING: Access (return to education), leisure and vocational courses at Further Education Colleges in the Midlands, UK. PARTICIPANTS: Healthy adults with a wide range of educational backgrounds and ages. INVESTIGATIONS: Participants read hypothetical scenarios and wrote brief answers to subsequent questions. Sub-samples of participants were interviewed individually to elaborate on their written answers. Participants' background assumptions concerning equipoise and randomisation were examined and ways of helping participants recognise the scientific benefits of randomisation were explored. MAIN OUTCOME MEASURES: Judgments on allocation methods; treatment preferences; the acceptability of random allocation; whether or not individual doctors could be completely unsure about the best treatment; whether or not doctors should reveal treatment preferences under conditions of collective equipoise; and how sure experts would be about the best treatment following random allocation vs doctor/patient choice. Assessments of understanding hypothetical trial information. RESULTS: Recent literature continues to report trial participants' failure to understand or remember information about randomisation and equipoise, despite the provision of clear and readable trial information leaflets. In current best practice, written trial information describes what will happen without offering accessible explanations. As a consequence, patients may create their own incorrect interpretations and consent or refusal may be inadequately informed. In six investigations, most participants identified which methods of allocation were random, but judged the random allocation methods to be unacceptable in a trial context; the mere description of a treatment as new was insufficient to engender a preference for it over a standard treatment; around half of the participants denied that a doctor could be completely unsure about the best treatment. A majority of participants judged it unacceptable for a doctor to suggest letting chance decide when uncertain of the best treatment, and, in the absence of a justification for random allocation, participants did not recognise scientific benefits of random allocation over normal treatment allocation methods. The pattern of results across three intervention studies suggests that merely supplementing written trial information with an explanation is unlikely to be helpful. However, when people manage to focus on the trial's aim of increasing knowledge (as opposed to making treatment decisions about individuals), and process an explanation actively, they may be helped to understand the scientific reasons for random allocation. CONCLUSIONS: This research was not carried out in real healthcare settings. However, participants who could correctly identify random allocation methods, yet judged random allocation unacceptable, doubted the possibility of individual equipoise and saw no scientific benefits of random allocation over doctor/patient choice, are unlikely to draw upon contrasting views if invited to enter a real clinical trial. This suggests that many potential trial participants may have difficulty understanding and remembering trial information that conforms to current best practice in its descriptions of randomisation and equipoise. Given the extent of the disparity between the assumptions underlying trial design and the assumptions held by the lay public, the solution is unlikely to be simple. Nevertheless, the results suggest that including an accessible explanation of the scientific benefits of randomisation may be beneficial provided potential participants are also enabled to reflect on the trial's aim of advancing knowledge, and to think actively about the information presented. Further areas for consideration include: the identification of effective combinations of written and oral information; helping participants to reflect on the aim of advancing knowledge; and an evidence-based approach to leaflet construction.
Adolescent↗
Adaptive allocation in randomized controlled trials.
Adaptive allocation has been proposed as a procedure to reduce the risk of chance imbalance of important prognostic factors in randomized controlled trials when the number of prognostic factors is large. In this article, minimization, a type of adaptive allocation, is compared to simple randomization and stratified allocation in a series of Monte Carlo simulations. Three outcomes are studied: estimated treatment effect, size of the rejection region, and power. Minimization produced an unbiased estimate of treatment effect and increased power when compared to simple randomization. Student's t test was conservative for both minimization and stratified allocation. Minimization and stratification produced similar improvements in power but there was some evidence that minimization might produce higher power than stratification when some prognostic variables cannot be included in the stratified allocation scheme.
Analysis of Variance↗
Inositol for respiratory distress syndrome in preterm infants.
BACKGROUND: Inositol is an essential nutrient required by human cells in culture for growth and survival. Inositol promotes maturation of several components of surfactant and may play a critical role in fetal and early neonatal life. OBJECTIVES: To assess the effectiveness/safety of supplementary inositol in preterm infants with RDS in reducing adverse neonatal outcomes. SEARCH STRATEGY: Medline, Embase, and Reference Update Databases were searched in August 1997 using key words: inositol and infant-newborn and random allocation or controlled trial or randomized trial (RCT). The reference lists of identified RCTs, personal files and Science Citation Index were searched. Unpublished additional information was obtained from the authors of one RCT published in abstract form. SELECTION CRITERIA: All randomized controlled trials of inositol supplementation to preterm infants with a control group that received a placebo or no intervention were included. Outcomes of interest were bronchopulmonary dysplasia (BPD), death, BPD or death, retinopathy of prematurity (ROP), intraventricular hemorrhage (IVH), necrotizing enterocolitis (NEC), and sepsis. DATA COLLECTION AND ANALYSIS: Data on neonatal outcomes were abstracted independently by the two researchers and any discrepancy was resolved through consensus. Revman was used for analysis of the data. MAIN RESULTS: Four reports of three RCTs were identified. One report was a duplicate publication. The outcome of death or bronchopulmonary dysplasia was reported in two trials, and was found to be significantly reduced (RR 0.56, 95% CI 0.42, 0.77; RD -0.215, 95% CI -0.323, -0.107). The outcome of death was reported in two trials and was found to be significantly reduced (RR 0.48, 95% CI 0.28, 0.80; RD -0.131, 95% CI -0.218, -0.043). Retinopathy of prematurity, stage 4 or needing therapy, was reported in two trials, and was found to be significantly reduced (RR 0.09, 95% CI 0.01, 0.67; RD -0.078, 95% CI -0.128, -0.027). Intraventricular hemorrhage, grade III-IV, was significantly decreased (RR 0.55, 95% CI 0.32, 0.95; RD -0.090, 95% CI -0.170, -0.010). Neither sepsis nor necrotizing enterocolitis outcomes were increased. When a secondary analysis was done excluding a study published in abstract form, the results differed only in that there was a significant reduction in retinopathy of prematurity, any stage (RR 0.53, 95% CI 0.29, 0.97; RD -0.082, 95% CI -0.159,-0.005). REVIEWER'S CONCLUSIONS: Inositol supplementation results in statistically significant and clinically important reductions in important short-term adverse neonatal outcomes. A multi-center RCT of appropriate size is justified to confirm these findings.
Dietary Supplements↗
Clinical trial of six-month and four-month regimens of chemotherapy in the treatment of pulmonary tuberculosis: the results up to 30 months.
In a study in Singapore, Chinese, Malay and Indian patients with pulmonary tuberculosis received 2 months of daily treatment with streptomycin, isoniazid, rifampicin, and pyrazinamide followed by daily isoniazid, and rifampicin either with pyrazinamide (SHRZ/HRZ) or without it (SHRZ/HR), allocated at random. Both regimens were given for either 6 or 4 months by random allocation. All 330 patients with drug-sensitive tubercle bacilli pretreatment had a favourable bacteriological response during chemotherapy. After chemotherapy none of 78 SHRZ/HRZ patients and only 2 of 80 SHRZ/HR patients treated for 6 months relapsed bacteriologically, but 9 (11%) of 79 SHRZ/HRZ and 6 (8%) of 77 SHRZ/HR patients treated for 4 months relapsed. Of 33 patients with bacilli resistant to isoniazid, streptomycin, or both drugs pretreatment, only 1 had an unfavourable response during chemotherapy; none of 9 patients treated for 6 months and 2 of 22 treated for 4 months relapsed bacteriologically after stopping chemotherapy.
Adolescent↗
Informed consent and participant perceptions of influenza vaccine trials in South Africa.
BACKGROUND AND OBJECTIVES: There are few insights from sub-Saharan Africa on research participants' experiences of the informed consent process, particularly in the context of randomised controlled trials, where issues of randomisation and the use of placebos may be confusing concepts for participants. This study investigated the knowledge and perceptions of the informed consent process among individuals participating in influenza vaccine trials in two disadvantaged communities in South Africa. METHOD: Four to 12 months after completion of the trials, participants were contacted to return to participate in the informed consent study. The semistructured questionnaire administered to assess recall of trial procedures and the informed consent process covered key issues including: purpose of the study; awareness that the study was not part of routine treatment; voluntary nature of participation and freedom to withdraw; randomisation; placebos; and remuneration. RESULTS: A total of 334 participants (93% of the original vaccine trial sample; mean age 68 years, median level of education grade 8, 69% women) completed the questionnaire. Only 21% were able to recall that they were allocated randomly to the different treatment arms. Only 19% of those involved in the placebo controlled study had interpreted the concept of placebo as an inactive medication. CONCLUSION: Although a good general recall of trial concepts was demonstrated, only a small proportion of the participants correctly interpreted and recalled the concepts of randomisation and placebos. Informed consent in this and similarly disadvantaged communities may often be inadequate and new ways to improve understanding of the research process should be explored.
Administration, Intranasal↗
Integrating patient preferences in clinical trials: a pilot study of acupuncture versus midazolam for gastroscopy.
BACKGROUND AND OBJECTIVES: Patient preferences play an important role when choosing between different treatment options and may have an influence on outcome. We performed a study to investigate (1) to what extent patients make use of the offer to receive acupuncture as a pretreatment for gastroscopy, (2) whether this is perceived as being as effective as sedation, and (3) whether characteristics and outcomes differ between patients giving consent to random allocation and patients choosing their pretreatment. DESIGN: Partially randomized patient preference trial. Patients who gave consent to randomization were allocated randomly while patients who had a preference received the treatment of their choice. PATIENTS: One hundred and six (106) inpatients of a district hospital in southern Germany undergoing gastroscopy for diagnostic purposes. INTERVENTIONS: Pretreatment with a sedative (midazolam) or acupuncture. MAIN OUTCOME MEASURE: Patient's overall assessment on a visual analogue scale (VAS). RESULTS: Twenty-eight (28) patients (26%) agreed to be randomized, 21 (20%) chose acupuncture, 51 (47%) midazolam, and 8 (7%) did not want pretreatment. Patients receiving midazolam rated the examination as slightly less troublesome than those receiving acupuncture. Oxygen saturation, blood pressure, and heart rate were significantly lower in patients receiving midazolam. Characteristics and outcomes of randomized and nonrandomized patients did not differ significantly. CONCLUSIONS: Because of the low number of patients giving consent to random allocation conclusions on effectiveness are difficult to draw. The partially randomized patient preference design is recommended for use in future trials of acupuncture for gastroscopy. Such trials should be performed in an outpatient setting.
Acupuncture Therapy↗
Randomisation in trials: do potential trial participants understand it and find it acceptable?
OBJECTIVE: To examine lay persons' ability to identify methods of random allocation and their acceptability of using methods of random allocation in a clinical trial context. DESIGN: Leaflets containing hypothetical medical, non-medical, and clinical trial scenarios involving random allocation, using material from guidelines for trial information leaflets. SETTING AND PARTICIPANTS: Adults attending further education colleges (n = 130), covering a wide range of ages, occupations, and levels of education. MAIN MEASURES: Judgements of whether each of five methods of allocation to two groups was random in a medical or non-medical scenario. Judgements of whether these allocation methods were acceptable in a randomised clinical trial scenario, with or without a scientific justification for randomisation. RESULTS: The majority of our group of participants judged correctly that allowing people their preference was not random, and that the following were random: using a computer with no information about the individual (recommended wording for MREC trial leaflets), tossing a coin, drawing a name out of a hat. Judgements were split over allocating people in turn (not a random allocation method but shares features with randomisation). Judgements were no different in medical and non-medical scenarios. Few of the correctly identified random methods were judged to be acceptable in a clinical trial scenario. Inclusion of a scientific justification for randomising significantly increased the acceptability of only one random method: allocation by computer. CONCLUSIONS: Current UK guidelines' recommended description of random allocation by computer seems warranted. However, while potential trial participants may understand what random allocation means, they may find it unacceptable unless offered an acceptable justification for its use.
Adolescent↗
Explanatory and pragmatic estimates of the treatment effect when deviations from allocated treatment occur.
In a randomized clinical trial comparing two treatments it can happen that certain patients receive the treatment other than that determined by random allocation. Significance testing is usually performed by 'intention to treat', that is, comparison of groups as determined by random allocation. The difference between the mean values of the outcome variable for these two groups estimates the difference in practical use between two treatment policies, corresponding to a pragmatic approach. An attenuation factor can then be used to obtain an estimate of the underlying difference in effectiveness between the two treatments, corresponding to an explanatory paradigm. Thus two distinct estimates are obtained; in many instances both are valid, but have distinct interpretations. Correspondingly, in planning sample size requirements when deviations from allocated treatment can be anticipated, the target treatment difference may be understood in either an explanatory or a pragmatic sense; for the sample size assessment method it is necessary to take this distinction into account.
Analgesics↗
Thrombosis prevention trial: randomised trial of low-intensity oral anticoagulation with warfarin and low-dose aspirin in the primary prevention of ischaemic heart disease in men at increased risk. The Medical Research Council's General Practice Research Framework.
BACKGROUND: We aimed to evaluate low intensity oral anticoagulation with warfarin and low-dose aspirin in the primary prevention of ischaemic heart disease (IHD). METHODS: 5499 men aged between 45 years and 69 years at high risk of IHD were recruited from 108 practices in the UK that belong to the Medical Research Council's General Practice Research Framework. Initially, warfarin or placebo was randomly allocated to 1427 men; 1013 of these men later moved to a factorial stage of the trial, retaining their warfarin or placebo warfarin allocation and adding randomly allocated active or placebo aspirin. Another 4072 men entered directly into the factorial stage making a total of 5085 men. The four factorial treatment groups were: active warfarin and active aspirin (WA, n = 1277), active warfarin and placebo aspirin (W, n = 1268), and placebo warfarin and active aspirin (A, n = 1268), and placebo warfarin and placebo aspirin (P, n = 1272). The primary end-point was all IHD defined as the sum of coronary death and fatal and non-fatal myocardial infarction (MI). FINDINGS: The mean International Normalised Ratio (INR) of those on active warfarin was 1.47. The mean warfarin dose was 4.1 mg a day (range 0.5 mg-12.5 mg). There were 410 IHD events (142 fatal, 268 non-fatal). The main effect of warfarin (i.e., WA and W vs A and P) was a reduction in all IHD of 21% (95% CI 4-35, p = 0.02) chiefly due to a 39% reduction (15-57, p = 0.003) in fatal events so that warfarin reduced the death rate from all causes by 17% (1-30, p = 0.04). The main effect of aspirin (i.e., WA and A vs W and P) was a reduction in all IHD of 20% (1-35, p = 0.04) almost entirely due to a 32% reduction (12-48, p = 0.004) in non-fatal events. Absolute reductions in all IHD due to warfarin or aspirin were 2.6 and 2.3 per 1000 person years, respectively. WA reduced all IHD by 34% (11-51, p = 0.006) compared with P. WA increased haemorrhagic and fatal strokes. Ruptured aortic or dissecting aneurysms occurred in 15 of those who were or had been on warfarin compared with three of those who had not (p = 0.01). INTERPRETATION: These results add to evidence that aspirin reduces non-fatal IHD. Warfarin reduced all IHD chiefly because of an effect on fatal events. Combined treatment with warfarin and aspirin is more effective in the reduction of IHD than either agent on its own.
Administration, Oral↗
Vaginal misoprostol for cervical ripening and labour induction in late pregnancy.
BACKGROUND: Although not yet registered for such use, misoprostol has been widely used for obstetric and gynaecological indications, such as induction of abortion and of labour. OBJECTIVES: The objective of this review was to assess the effects of vaginal misoprostol for third trimester cervical ripening or induction of labour. SEARCH STRATEGY: The Cochrane Pregnancy and Childbirth Group trials register, the Cochrane Controlled Trials Register and reference lists of articles were searched. SELECTION CRITERIA: Randomised trials comparing vaginal misoprostol with other methods of cervical ripening or labour induction, placebo or no treatment in women due for third trimester induction of labour. DATA COLLECTION AND ANALYSIS: Trial quality assessment and data extraction were done by both reviewers. MAIN RESULTS: Twenty-six studies were included. Compared to placebo, misoprostol was associated with increased cervical ripening (relative risk of unfavourable or unchanged cervix after 12 to 24 hours with misoprostol 0.20, 95% confidence interval 0.07 to 0.61). It was also associated with a reduced need for oxytocin (relative risk 0.47, 95% confidence interval 0.23 to 0.96). Misoprostol was more effective than prostaglandin E2 for labour induction (relative risk of failure to achieve vaginal delivery in 24 hours 0.70, 95% confidence interval 0.62 to 0.79). Oxytocin augmentation was used less often with misoprostol than with prostaglandin E2 (relative risk 0.64, 95% confidence interval 0.58 to 0.71). Uterine hyperstimulation and meconium stained liquor were more common with misoprostol than with prostaglandin E2. Lower doses of misoprostol compared to higher doses did not show significant differences except for more need for oxytocin augmentation and less uterine hyperstimulation without fetal heart rate changes. REVIEWER'S CONCLUSIONS: Vaginal misoprostol appears to be more effective in inducing labour than conventional methods of cervical ripening and labour induction. The apparent increase in uterine hyperstimulation is of concern. The studies were not large enough to exclude the possibility of rare but serious adverse effects.
Cervical Ripening↗