Efficiency optimization of the selection period in therapeutic trials.

To determine eligibility for a (randomized) clinical trial, measuring the inclusion and exclusion criteria can be extended over a period of time. During this period, known as the selection period, a patient is repeatedly examined at certain time intervals. This study describes an approach for optimizing the efficiency of the selection period. Efficiency is defined as the costs of randomizing one patient. The objective is to construct prediction models based on data obtained early in the selection period to predict subsequent exclusions. A prediction model increases the efficiency if after its application the costs per randomization are lower. The approach is illustrated using data from the selection period of the Rotterdam Cardiovascular Risk Intervention (ROCARI) trial which was composed of five consecutive patient visits. At each visit, data to determine eligibility was obtained. We found that logistic regression models based on data of the first and second visit could predict exclusions during the third visit. Application of the prediction models suggested that in this particular trial the costs per randomization would decrease by $52. As the initial costs per randomization were $1444, there would be a 3.6% (52/1444) savings in recruitment costs under the prediction models, accounting for a savings of more than $450,000. We conclude that the use of data obtained early in a selection period can predict subsequent exclusions, and therefore could increase the efficiency of such a period. The approach could be applied to data obtained in a pilot study as well as data obtained in the beginning of a prolonged intake period.

Costs and effects of long-term oral anticoagulant treatment after myocardial infarction.

OBJECTIVE: To investigate the costs and effects of long-term oral anticoagulant treatment after myocardial infarction. DESIGN: Cost-effectiveness analysis, based on a randomized, double-blind, placebo-controlled trial. SETTING: Sixty Dutch hospitals. PATIENTS: A total of 3404 hospital survivors of acute myocardial infarction randomized within a median period of 4 days after discharge to either oral anticoagulant treatment or placebo. The mean follow-up was 37 months. INTERVENTION: Oral anticoagulant treatment aimed at a target international normalized ratio of 2.8 to 4.8. MAIN OUTCOME MEASUREMENTS: Costs of hospital stay during readmissions, costs related to major cardiologic interventions, and costs of oral anticoagulant treatment. RESULTS: The costs of oral anticoagulant treatment were estimated at 394 Dutch guilders (Dfl) per patient-year (Dfl 1 = US $0.58). Placebo patients stayed 18,830 days in the hospital compared with 15,083 days for anticoagulation patients. Average costs per patient of medical care during follow-up were estimated at Dfl 10,784 for placebo patients and Dfl 9878 for anticoagulation patients. CONCLUSIONS: Costs of long-term anticoagulant treatment are outweighed by the costs of prevented clinical events.

[Adjustment to insulin of patients with type II diabetes mellitus in primary care; good results at low cost]. / Instelling op insuline van patiënten met diabetes mellitus type II in de eerste lijn; goede resultaten bij geringe kosten.

OBJECTIVE: Comparison of costs and results of different treatment policies for patients with diabetes mellitus type II (NIDDM) starting on insulin. DESIGN: Retrospective study using literature control data. SETTING: Diabetes Centre Rotterdam (DCR). METHODS: The effects of home treatment by the DCR were studied during one year in 52 NIDDM patients by measurement of glycosylated haemoglobin (HbA1c) values. These effects were compared with literature data. Cost data of insulin treatment were calculated for the different policies. RESULTS: After one year of insulin treatment, the DCR patients had 'satisfactory' HbA1c levels according to international standards. In comparable patients treated at an outpatient clinic these values were 'poor'. Home treatment versus treatment at an outpatient clinic or during hospitalisation constituted a cost reduction of NFL 416 and NFL 2480 per patient respectively. CONCLUSION: Insulin treatment in NIDDM patients at home has at least the same effects on HbA1c values as obtained in patients treated at an outpatient clinic, and reduces costs.

Assessment of therapeutic quality control in a long-term anticoagulant trial in post-myocardial infarction patients.

Various methods have been described to evaluate efficacy of anticoagulant therapy using the international normalized ratio (INR). We compared the following approaches: (1) total INR's or the most recent measurement; (2) percent time within therapeutic range, with INR changing directly or halfway between visits; and (3) total observation time assuming INR changing linearly. The study population comprised 1700 post myocardial infarction patients. Treatment comprised 3725 patient-years. There were 61,471 INR assessments with target therapeutic level of 2.8-4.8. Acenocoumarol as well as phenprocoumon were employed. Therapeutic achievement in the first months of treatment was low: less than 60% of INR's were in range. Treatment stabilized after 6 months. Patients on acenocoumarol were within range 70% of the time compared to 80% for phenprocoumon. Method 3 is preferred because it incorporates time and is capable of calculating incidence rates at different INR levels. Our findings call for an urgent improvement of standard of anticoagulant control in the first months following commencement of treatment.