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K F Schulz

Publications and source records attributed to K F Schulz.

At least 73 records · Page 4Linked to original sources
PubMed1996

Determining sample size and power in clinical trials: the forgotten essential.

Estimation of the sample size is a fundamental but usually ignored requirement of the randomized controlled trial (RCT). Indeed, the publication of small trials without consideration of sample size is worrisome from both medical and ethical viewpoints. Type II errors are common, and readers and investigators may reject worthwhile treatments and interventions. Before embarking on an RCT, the investigator must choose an alpha, a beta, and the rates of outcomes anticipated in both treatment groups. This should reflect the characteristics of the condition and its treatment. If limited sample size or available resources pose a problem, the use of continuous outcome measures, paired before-after measurements, and more common outcome measures can minimize sample size requirements. If these approaches are not satisfactory, then a multicenter trial may be in order.

Clinical Trials as Topic↗
PubMed1995

Subverting randomization in controlled trials.

Recent empirical evidence supports the importance of adequate randomization in controlled trials. Trials with inadequate allocation concealment have been associated with larger treatment effects compared with trials in which authors reported adequate allocation concealment. While that provides empirical evidence of bias being interjected into trials, trial investigators rarely document the sensitive details of subverting the intended purpose of randomization. This article relates anonymous accounts run the gamut from simple to intricate operations, from transillumination of envelopes to searching for code in the office files of the principal investigator. They indicate that deciphering is something more frequent than a rate occurrence. These accounts prompt some methodological recommendations to help prevent deciphering. Randomized controlled trials appear to annoy human nature--if properly conducted, indeed they should.

Random Allocation↗
PubMed1995

Unbiased research and the human spirit: the challenges of randomized controlled trials.

Research by Klein and associates provides useful information on the relation between episiotomy and outcomes such as perineal trauma, but the methodologic implications of their work are especially fascinating. Physicians who participated in their randomized controlled trial (RCT) were supposed to adhere to a policy of either liberal or restrictive use of episiotomy according to the study arm to which each patient was assigned. However, some used the procedure for approximately 90% of patients regardless of allocation. Klein and associates' post-hoc study (see pages 769 to 779 of this issue) sheds light on the relation between physician attitudes and the practice of episiotomy. The author contends that the noncompliance encountered by Klein and associates reflects the fact that randomized trials are anathema to the human spirit. He offers suggestions for making RCTs more meaningful and stresses that, although RCTs are indispensible to the advancement of medical knowledge, they necessitate assiduous attention to matters of design and implementation.

Attitude of Health Personnel↗
PubMed1995

The methodologic quality of randomization as assessed from reports of trials in specialist and general medical journals.

OBJECTIVE: To assess the quality of randomization from reports of trials in a sample of specialist journals, and to compare those results with a similar assessment from a sample of general medical journals. DESIGN: Evaluation of all 206 reports of parallel-group randomized trials published in the 1990 and 1991 volumes of four journals of obstetrics and gynecology and of 81 reports of trials published during 1987 in four general medical journals. RESULTS: Of the reports published in the specialist and in the general medical journals, only 32% and 48%, respectively, reported having used an adequate method to generate random numbers; only 23% and 26%, respectively, contained information showing that steps had been taken to conceal assignment until the point of treatment allocation; and merely 9% and 15%, respectively, described adequate methods of both sequence generation and allocation concealment. In those reports of trials that had apparently used unrestricted randomization, the differences in sample sizes between treatment and control groups were much smaller than would be expected by chance, and that feature was more marked in the specialist journals. In reports of trials in which hypothesis tests had been used to compare baseline characteristics, only 2% of tests reported in specialist journals and 4% of tests reported in general journals were statistically significant, lower than the expected rate of 5%. CONCLUSIONS: Generating unbiased comparison groups requires proper randomization, yet the reports in these specialist and general journals usually provided inadequate or unacceptable information. Additional analyses suggest that nonrandom manipulation of comparison groups and selective reporting of baseline comparisons may have occurred.

Gynecology↗
PubMed1995

Empirical evidence of bias. Dimensions of methodological quality associated with estimates of treatment effects in controlled trials.

OBJECTIVE: To determine if inadequate approaches to randomized controlled trial design and execution are associated with evidence of bias in estimating treatment effects. DESIGN: An observational study in which we assessed the methodological quality of 250 controlled trials from 33 meta-analyses and then analyzed, using multiple logistic regression models, the associations between those assessments and estimated treatment effects. DATA SOURCES: Meta-analyses from the Cochrane Pregnancy and Childbirth Database. MAIN OUTCOME MEASURES: The associations between estimates of treatment effects and inadequate allocation concealment, exclusions after randomization, and lack of double-blinding. RESULTS: Compared with trials in which authors reported adequately concealed treatment allocation, trials in which concealment was either inadequate or unclear (did not report or incompletely reported a concealment approach) yielded larger estimates of treatment effects (P < .001). Odds ratios were exaggerated by 41% for inadequately concealed trials and by 30% for unclearly concealed trials (adjusted for other aspects of quality). Trials in which participants had been excluded after randomization did not yield larger estimates of effects, but that lack of association may be due to incomplete reporting. Trials that were not double-blind also yielded larger estimates of effects (P = .01), with odds ratios being exaggerated by 17%. CONCLUSIONS: This study provides empirical evidence that inadequate methodological approaches in controlled trials, particularly those representing poor allocation concealment, are associated with bias. Readers of trial reports should be wary of these pitfalls, and investigators must improve their design, execution, and reporting of trials.

Bias↗
PubMed1995

The cofactor effect of genital ulcers on the per-exposure risk of HIV transmission in sub-Saharan Africa.

The goal was to estimate the cofactor effect of genital ulcer disease (GUD) on the risk of HIV transmission during a single heterosexual exposure. The relation between the risk ratio observed in an epidemiological study and the per-exposure cofactor effect was investigated. Given simple assumptions, we show that observed risk ratios are expected to be very much smaller than per-exposure cofactor effects and to decrease as the observation period increases. Data from longitudinal studies of female commercial sex workers and men in Nairobi were reanalysed. The data are consistent with GUD cofactor effects per sexual exposure of 10-50 for male to female transmission, and of 50-300 for female to male transmission. Although subject to wide margins of error, these estimates indicate that GUD may be responsible for a high proportion of heterosexually acquired HIV infections in sub-Saharan Africa, supporting the potential role of STD control as an effective intervention strategy against HIV.

Africa South of the Sahara↗
PubMed1994

Assessing the quality of randomization from reports of controlled trials published in obstetrics and gynecology journals.

OBJECTIVE: To assess the methodologic quality of approaches used to allocate participants to comparison groups in randomized controlled trials from one medical specialty. DESIGN: Survey of published, parallel group randomized controlled trials. DATA SOURCES: All 206 reports with allocation described as randomized from the 1990 and 1991 volumes of four journals of obstetrics and gynecology. MAIN OUTCOME MEASURES: Direct and indirect measures of the adequacy of randomization and baseline comparisons. RESULTS: Only 32% of the reports described an adequate method for generating a sequence of random numbers, and only 23% contained information showing that steps had been taken to conceal assignment until the point of treatment allocation. A mere 9% described both sequence generation and allocation concealment. In reports of trials that had apparently used unrestricted randomization, the differences in sample sizes between treatment and control groups were much smaller than would be expected due to chance. In reports of trials in which hypothesis tests had been used to compare baseline characteristics, only 2% of reported test results were statistically significant, lower than the expected rate of 5%. CONCLUSIONS: Proper randomization is required to generate unbiased comparison groups in controlled trials, yet the reports in these journals usually provided inadequate or unacceptable information on treatment allocation. Additional analyses suggest that nonrandom manipulation of comparison groups and selective reporting of baseline comparisons may have occurred.

Gynecology↗
PubMed1993

Immunization as therapy for recurrent spontaneous abortion: a review and meta-analysis.

OBJECTIVE: To determine the efficacy of immunotherapy as treatment for recurrent spontaneous abortion (three or more consecutive abortions without an intervening pregnancy of more than 20 weeks' gestation) using meta-analysis. DATA SOURCES: The search began with MEDLINE and was supplemented by reference lists from original research, review articles, and textbooks. We also corresponded with investigators and consulted experts in the field of infertility. METHODS OF STUDY SELECTION: We identified four randomized controlled trials and 19 case-series reports that examined the use of immunotherapy for recurrent spontaneous abortion. DATA EXTRACTION AND SYNTHESIS: A meta-analysis performed on four randomized controlled trials of leukocyte immunotherapy or trophoblast membrane infusion revealed a fixed-effects model odds ratio of 1.3 (95% confidence interval [CI] 0.77-2.3) and a random-effects model odds ratio of 1.3 (95% CI 0.44-3.8). CONCLUSION: The quality of evidence regarding this treatment is class I (best), and the strength of recommendation is D (fair evidence against its use). Unless its efficacy can be established through other randomized controlled trials, this treatment should be abandoned.

Abortion, Habitual↗
PubMed1992

Randomized controlled trials of home uterine activity monitoring: a review and critique.

Home uterine activity monitoring has been proposed as an effective technique for reducing the incidence of preterm birth by early recognition of incipient labor. Five randomized controlled trials evaluating this technique have been published in peer review journals. As judged by accepted criteria for such trials, all have serious methodologic deficiencies. Four of the five trials demonstrated no significant benefit from this monitoring. Two other trials not published in peer review journals support the hypothesis that home uterine activity monitoring is no more effective than daily nursing contact. Until the efficacy of this technology has been established, home uterine activity monitoring should not be used clinically.

Evaluation Studies as Topic↗
PubMed1990

Preventing IUCD-related pelvic infection: the efficacy of prophylactic doxycycline at insertion.

Most of the small increased risk in pelvic inflammatory disease (PID) associated with the intrauterine contraceptive device (IUCD) appears to be caused by bacterial contamination of the endometrial cavity at the time of insertion. This randomized clinical trial of 1813 women in Nairobi, Kenya, assessed the effectiveness of 200 mg of doxycycline given orally at the time of insertion in reducing the occurrence of PID. The rate of this infection in the doxycycline-treated group was 31% lower than that in the placebo-treated group (1.3 and 1.9%, respectively; RR 0.69; 95% CI 0.32 to 1.5). The rate of an unplanned IUCD-related visit to the clinic was also 31% lower in the doxycycline-treated group (RR 0.69; 95% CI 0.52 to 0.91). Although the significance level (P = 0.17) for the reduction is PID does not meet the conventional standard of 0.05, the results may be suggestive of an effect. Moreover, the reduction in IUCD-related visits (P = 0.004) not only represents an important decrease in morbidity but also substantiates the reduction found for PID. Further studies are needed to corroborate these results. Consideration should be given to the prophylactic use of doxycycline at the time of IUCD insertion as an approach to preventing PID and other IUCD-related morbidity.

Adult↗
PubMed1987

Pregnancy loss, infant death, and suffering: legacy of syphilis and gonorrhoea in Africa.

Africa in the 1980s appears to be facing problems associated with syphilis and gonorrhoea during pregnancy similar in severity and magnitude to those faced by the western world in the early 1900s. From a review of published reports, the prevalence of syphilis seroreactivity in pregnant women in many parts of Africa is at least 10%. Assuming this level of seroreactivity, we estimate that 5% to 8% of all pregnancies surviving past 12 weeks will have an adverse outcome caused by syphilis, such as spontaneous abortion, perinatal or infant death, or a living infant with syphilis. Our findings on gonorrhoea during pregnancy are almost as startling. The prevalence of gonorrhoea in pregnant women in many parts of Africa is at least 10% and it approaches 20% in some areas. The incidence of gonococcal ophthalmia neonatorum in neonates appears to be between 2% and 4%. We recommend commitment of health resources to initiatives to prevent and control sexually transmitted disease in Africa and additional research into the cost effectiveness of different prevention and control approaches.

Abortion, Spontaneous↗
PubMed1985

The risk of serious complications from induced abortion: do personal characteristics make a difference?

We examined the age, gestational age, parity, race, and number of previous spontaneous and induced abortions of 82,030 women who obtained abortions at less than or equal to 24 weeks' gestation. Among these women, 342 (0.4%) had serious complications, including 130 (0.2%) with fever greater than or equal to 38 degrees C for 3 or more days, 172 (0.2%) who required transfusions, 67 (0.1%) who required unintended surgery, and three who died. Factors significantly (p less than 0.05) associated with serious complications varied by period of gestation, including previous induced abortions (adjusted relative risk = 1.57, 95% confidence interval = 1.03 to 2.40) for procedures done at less than or equal to 12 weeks' gestation, advancing age (relative risk for a 5-year increment = 1.12, 95% confidence interval = 1.01 to 1.24), and advancing gestational age (relative risk for a 2-week increment = 1.50, 95% confidence interval = 1.43 to 1.57) for procedures done at greater than 12 weeks, and greater than or equal to 1 previous delivery (relative risk = 1.34, 95% confidence interval = 1.03 to 1.75) for all gestational ages. Although Hispanic women had higher rates of complications compared with white women, data were not available to control for socioeconomic status in comparing race groups. There was no significant association between previous spontaneous abortions and serious complications. Risk patterns were similar, but not identical, when fever, operation, and transfusion were considered separately.

Abortion, Induced↗
PubMed1985

Preventing febrile complications of suction curettage abortion.

To identify risk factors for febrile complications after suction curettage abortion, we analyzed the data of 26,332 women who underwent suction curettage abortion at five participating centers in the Joint Program for the Study of Abortion, Part III, from 1975 to 1978. We defined febrile morbidity as an oral temperature of greater than or equal to 38 degrees C for 2 days or longer. The febrile morbidity rate was 0.34 per 100 abortions. We performed a multivariate analysis using a linear logistic regression model. Prophylactic antibiotics proved to be the most protective factor, reducing the rate of febrile complications to about one third that of women who received no prophylactic antibiotics (relative risk 0.36; 95% confidence interval 0.18 to 0.70). Patients who had had one or more previous births also had a significantly lower risk of febrile morbidity (relative risk 0.54; 95% confidence interval 0.33 to 0.88). Other factors did not significantly affect the febrile complication rate.

Abortion, Induced↗