Validating literature-based models with direct clinical trial results: the cost-effectiveness of secondary prophylaxis for PCP in AIDS patients.

OBJECTIVE

To compare literature-based estimates of the cost-effectiveness ratios of strategies for secondary prophylaxis of Pneumocystis carinii pneumonia (PCP) in AIDS patients with estimates obtained using data from a recent comparative clinical trial.

DESIGN

A decision-analytic Markov model with data on drug efficacy and toxicity from both the medical literature and a national randomized clinical trial. Drug costs were from average wholesale prices. Discounted life expectancy, total direct medical costs, and cost-effectiveness were projected in dollars per year of life saved (YLS).

SETTING

Hypothetical for the literature-based model, then the clinical trial results from the multicenter AIDS Clinical Trials Group (ACTG Protocol 021).

PATIENT POPULATION

Patients with AIDS and a prior episode of PCP.

INTERVENTIONS

Strategies included no prophylaxis, TMP-SMX (160/800 mg) daily, or aerosolized pentamidine (300 mg) monthly. Patients experiencing major toxic reactions to either medication would cross over to the other agent.

MAIN RESULTS

In the literature-based model no prophylaxis was associated with a projected life expectancy of 1.430 years, and total direct cost of $42,080. TMP-SMX increased life expectancy to 2.051 years and cost to $42,300; for aerosolized pentamidine life expectancy was 2.066 years and cost $43,960. TMP-SMX had an incremental cost-effectiveness ratio of $350 per YLS compared with no prophylaxis; the incremental ratio for aerosolized pentamidine was $2,950 per YLS when compared with no prophylaxis, but rose to $110,880 per YLS compared with TMP-SMX. When data from ACTG clinical trial 021 were utilized in the model, the incremental cost-effectiveness ratio for TMP-SMX compared with no prophylaxis was $720 per YLS; aerosolized pentamidine was not cost-effective, and was "dominated" by TMP-SMX because it was associated with higher costs and shorter life expectancy.

CONCLUSIONS

Literature-based cost-effectiveness models are useful in developing health policy before clinical trials are completed. Clinical trial results, when available, can be used to validate and revise these models. For secondary PCP prophylaxis in AIDS patients, TMP-SMX is substantially more cost-effective than aerosolized pentamidine.