OBJECTIVE: To quantify the willingness of patients with chronic idiopathic thrombocytopenic purpura (ITP) to trade off different attributes of ITP treatments, including efficacy, safety, and mode of administration. To determine the level of benefits, which balanced risks when faced with discrete choices.
BACKGROUND: ITP is primarily a disorder of adults characterized by reduced platelet production and autoantibody-induced platelet destruction, leading to a low peripheral blood platelet count (<150 Gi/L; Cines, 2002). Patients may have few symptoms or may suffer bruising, purpura, or more serious complications, such as intracerebral bleeding. Treatment is aimed at elevating platelets to a hemostatic, safe range (≥50 to 400 Gi/L) to minimize the risk of bleeding. To date, the long-term management of patients with chronic ITP has been unsatisfactory, largely due to the variable efficacy, poor tolerability, and severe side effects associated with current treatment options. Treatment involves corticosteroids, intravenous immunoglobulins, immunosuppressive drugs, chemotherapy, splenectomy, and, more recently, monoclonal antibodies targeted against B cell antigens (Stasi, 2004). The relative importance of different treatment attributes from a patient perspective has not been previously studied.
METHODOLOGY: Participants were recruited through an ITP patient support group and were to have reported a diagnosis of chronic ITP. They completed an online survey that included a series of stated-choice trade-off tasks. Respondents chose between pairs of hypothetical treatment alternatives defined by a different likelihood of achieving hemostatic platelet levels, need for concomitant corticosteroids, mode of treatment administration, risk of rebound thrombocytopenia, risk of elevated liver enzymes resulting in treatment discontinuation, and risk of blood clot. Mixed-logit methods were used to estimate relative preference weights for treatment attribute levels; regression model parameter estimates were used to derive the maximum accepted risk (MAR) of adverse events for specific increases in the likelihood of treatment success and the minimum acceptable benefit (MAB) required to justify a given level of adverse-event risk.
RESULTS: The survey was completed by 1,542 respondents. Seventy-two percent of respondents were female, the mean age was 50 years, 92% were white, and 86% had education beyond high school. Patients with chronic ITP were willing to accept significant risks of side effects or adverse events to increase the likelihood of treatment success, to avoid the need for corticosteroids, and to attain a convenient mode of administration. In return for a 25–percentage-point increase in the likelihood of achieving a safe platelet level, patients were willing to accept an average risk for rebound thrombocytopenia of 18.8% (95% CI, 16.3%–21.3%). For avoiding corticosteroids, patients tolerated risk for rebound thrombocytopenia and blood clot of 20.2% (95% CI, 18.4%–23.7%) and 3.4% (95% CI, 2.7%–4.2%), respectively. Patients were willing to accept an additional risk of thromboembolism as high as 2% and a risk of liver-function test abnormalities or rebound thrombocytopenia as high as 13% if they could take 1 or 2 pills every day instead of going to a doctor’s office for an injection once a week. When given a choice and all other factors being equal, 71% of patients stated that they would surely or probably choose 1 to 2 pills a day, while 8% of patients stated they would choose weekly injections in a physician’s office (with remaining patients not stating a preference).
CONCLUSIONS: In this large, rigorously conducted study, patients with chronic ITP were willing to accept significant risks of thromboembolic events, liver abnormalities, and rebound thrombocytopenia for greater efficacy benefit, as well as to avoid the use of corticosteroids. The majority of patients also preferred an orally administered therapy to an injectable therapy administered in a physician’s office or at home.