Value of information: interim analysis of a randomized, controlled trial of goal-directed hemodynamic treatment for aged patients

Abstract

Background: A randomized, controlled trial, intended to include 460 patients, is currently studying peroperative goal-directed hemodynamic treatment (GDHT) of aged hip-fracture patients. Interim efficacy analysis performed on the first 100 patients was statistically uncertain; thus, the trial is continuing in accordance with the trial protocol. This raised the present investigation's main question: Is it reasonable to continue to fund the trial to decrease uncertainty? To answer this question, a previously developed probabilistic cost-effectiveness model was used. That model depicts (1) a choice between routine fluid treatment and GDHT, given uncertainty of current evidence and (2) the monetary value of further data collection to decrease uncertainty. This monetary value, that is, the expected value of perfect information (EVPI), could be used to compare future research costs. Thus, the primary aim of the present investigation was to analyze EVPI of an ongoing trial with interim efficacy observed.

Methods: A previously developed probabilistic decision analytic cost-effectiveness model was employed to compare the routine fluid treatment to GDHT. Results from the interim analysis, published trials, the meta-analysis, and the registry data were used as model inputs. EVPI was predicted using (1) combined uncertainty of model inputs; (2) threshold value of society's willingness to pay for one, quality-adjusted life-year; and (3) estimated number of future patients exposed to choice between GDHT and routine fluid treatment during the expected lifetime of GDHT.

Results: If a decision to use GDHT were based on cost-effectiveness, then the decision would have a substantial degree of uncertainty. Assuming a 5-year lifetime of GDHT in clinical practice, the number of patients who would be subject to future decisions was 30,400. EVPI per patient would be €204 at a €20,000 threshold value of society's willingness to pay for one quality-adjusted life-year. Given a future population of 30,400 individuals, total EVPI would be €6.19 million.

Conclusions: If future trial costs are below EVPI, further data collection is potentially cost-effective. When applying a cost-effectiveness model, statements such as 'further research is needed' are replaced with 'further research is cost-effective and 'further funding of a trial is justified'.

Trial registration: ClinicalTrials.gov NCT01141894.

Figure 1

Inclusion sequence of the first 100 randomized patients in the trial:ClinicalTrials.gov NCT01141894.

Figure 2

Cost-effectiveness model. A) Short-term model, the decision tree. The arrows represent the transition of the hypothetical patients towards the selected post-operative outcomes (triangles). These transitions are characterized by probability estimates (p1 to p10), costs, and health-related quality-of-life weights. For the routine fluid treatment, probability estimates were extracted from a cohort from Lund University Hospital [7]. * For goal-directed hemodynamic treatment (GDHT), the interim analysis was used. ** For mortality, published data on high-risk patients were used [8]. B) The long-term model, Markov structure. The hypothetical patients were allocated to health states characterized by health-related quality-of-life weights. During annual cycles of simulation, the patients transition in the model or stay in the same heath state. These transitions are characterized by probability estimates (p11 to p21). {AU After each cycle, quality-adjusted life-years and direct health-care costs are aggregated.

Figure 3

Incremental costs and effects (∆QALY) of goal-directed hemodynamic treatment (GDHT) versus routine fluid therapy. The dotted line represents one threshold value of how much society would be willing to pay for 1 additional life-year with full health for each patient in the target population.

Figure 4

The expected value of further information for the Swedish patient population aged >80 years with hip fracture. The expected value of perfect information (EVPI) is plotted against the willingness to pay per quality-adjusted life-year (cost-effectiveness threshold).