Major Randomized Controlled Trials Research Articles

Intravenous therapy in critically ill adults: developing a clinically and cost-effective approach

Intravenous therapies are the most common intervention for critically ill adults. Using a systematic approach as described by Droogan and Song (1996), a review of the literature was undertaken to determine whether the frequency of changing intravenous administration sets in critically ill adults with central venous catheters (CVCs) affected the incidence of CVC-related sepsis/systemic inflammatory response syndrome (SIRS)/bacteraemia. Two major randomized controlled trials were included in the review ( Maki et al. 1987; Snydman et al. 1987), which conclude that increasing the change frequency of administration sets from 24 to 72 hours does not significantly increase the incidence of sepsis. This can therefore lead to considerable cost savings as well as ensuring clinically effective care. The review criteria excluded a plethora of related studies. However, these studies do corroborate the findings of Maki et al. and Snydman et al. They are summarized in the tables and are taken into account when making recommendations for clinical practice and future research. Clinical practice guidelines which are being implemented and evaluated locally are offeredfor the reader's consideration.

The role of CA 125 in screening for ovarian cancer.

Ovarian cancer has the worst prognosis of any gynaecological malignancy, primarily because it tends to present at an advanced stage. The excellent survival rates of early stage disease have provided the rationale for efforts to detect ovarian cancer early by screening, in the hope that survival rates will be improved. Available data suggests that CA 125 is elevated in the majority of epithelial ovarian malignancies prior to clinical presentation. Large trials of screening for ovarian cancer indicate that using a CA 125 cutoff value of 30 U/mL has good sensitivity, but inadequate specificity for detecting preclinical disease. Use of transvaginal ultrasonography as a second-line test in women with elevated CA 125 levels improves specificity to acceptable levels, as does use of a mathematical algorithm which analyses rates of change of CA 125. Two major randomised controlled trials, investigating the effect of screening strategies incorporating CA 125 on mortality, are currently underway.

Costs and Effectiveness of Angiotensin Converting Enzyme Inhibition in Patients With Congestive Heart Failure

Chronic heart failure is associated with a poor prognosis and reduced survival rates. The addition of vasodilator drug therapy to conventional therapy for congestive heart failure has resulted in improved survival. Adopting a societal viewpoint, we designed a decision analytic model to analyze the costs and effectiveness of three therapies available for the treatment of congestive heart failure: standard therapy (digoxin and diuretic therapy) plus (1) no vasodilator agents, (2) hydralazine hydrochloride-isosorbide dinitrate combination, and (3) enalapril. In addition, we performed sensitivity analyses to determine which model variables were influential in determining incremental cost-effectiveness ratios (cost of drug, cost of hospitalization, efficacy of agents, etc). We used data from three major randomized controlled trials to estimate treatment efficacy, mortality rates, and hospitalization rates. An additional year of life gained by a patient receiving hydralazine-isosorbide combination therapy compared with standard therapy required an additional expense (incremental cost-effectiveness ratio) of $5600. Compared with the hydralazine-isosorbide combination therapy, the incremental cost-effectiveness ratio for enalapril therapy was $9700 per year of life saved. These results were insensitive to wide variations in our baseline assumptions. The cost per year of life saved by vasodilator therapy is much lower than that of other accepted medical therapies. Although the cost per year of life saved for hydralazine-isosorbide combination therapy is lower than that for enalapril therapy, enalapril therapy saves more lives, and the incremental cost of enalapril therapy is justified by the added benefits.

Report of the International Workshop on Screening for Breast Cancer.

Over the past 30 years, eight major randomized controlled trials of breast cancer screening--with mammography and/or clinical breast examination--have been conducted. Results from several trials have been updated during the past year, and initial results of three other trials have been reported. The National Cancer Institute held an International Workshop on Screening for Breast Cancer in February 1993 to conduct a thorough and objective critical review of the world's most recent clinical trial data on breast cancer screening, consider the new evidence, assess the current state of knowledge, and identify issues needing further research. Investigators representing the eight randomized controlled trials of breast cancer screening in women aged 40-74 presented published and unpublished data. Evidence relating to the effectiveness of breast cancer screening in different age groups, especially women aged 40-49, was presented. For women aged 40-49, randomized controlled trials consistently demonstrated no benefit from screening in the first 5-7 years after study entry. A meta-analysis of six trials found a relative risk of 1.08 (95% confidence interval = 0.85-1.39) after 7 years' follow-up. After 10-12 years of follow-up, none of four trials have found a statistically significant benefit in mortality; a combined analysis of Swedish studies showed a statistically insignificant 13% decrease in mortality at 12 years. Only one trial (Health Insurance Plan) has data beyond 12 years of follow-up, and results show a 25% decrease in mortality at 10-18 years. Statistical significance of this result is disputed, however. In women aged 50-69, all studies show mortality reductions; three of four studies show reductions of about 30% at 10-12 years after study entry. Results from two of these trials were statistically significant. Too few women over age 70 have been included in studies for adequate analysis. For women aged 40-49, randomized controlled trials of breast cancer screening show no benefit 5-7 years after entry. At 10-12 years, benefit is uncertain and, if present, marginal; thereafter, it is unknown. For women aged 50-69, screening reduces breast cancer mortality by about a third. Currently available data for women age 70 or older are inadequate to judge the effectiveness of screening. Randomized trials have provided stronger scientific evidence regarding the effectiveness of screening for breast cancer than for any other cancer. However, much still needs to be learned. Periodic gatherings of scientists in the field should speed the process.