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An Integrated Pharmacokinetic–Pharmacodynamic–Pharmacoeconomic Modeling Method to Evaluate Treatments for Adults with Schizophrenia


  • Marjanne A. Piena

    (OPEN Health)

  • Natalie Houwing

    (OPEN Health)

  • Carla W. Kraan

    (OPEN Health)

  • Xiaofeng Wang

    (Otsuka Pharmaceutical Companies)

  • Heidi Waters

    (Otsuka Pharmaceutical Companies)

  • Ruth A. Duffy

    (Otsuka Pharmaceutical Companies)

  • Suresh Mallikaarjun

    (Otsuka Pharmaceutical Companies
    Virginia Commonwealth University)

  • Craig Bennison

    (OPEN Health)


Introduction Schizophrenia is a chronic mental disorder that worsens with each relapse. Long-acting injectable (LAI) antipsychotics may prevent the exacerbation of symptoms and occurrence of relapses through improved continuity of care. Different dose regimens are available for the LAIs aripiprazole monohydrate (AM) and aripiprazole lauroxil (AL), but their cost effectiveness is unclear. Objectives The study aim was to compare costs and effects (relapses) of the different aripiprazole LAI dose regimens to inform clinical and US payer decisions. Methods A state-transition model calculated the outcomes of eight LAI dose regimens based on their relapse rates. As effectiveness data from randomized controlled trials were unavailable, relapse rates were modeled using pharmacokinetic and pharmacodynamic evidence. These described blood plasma levels of aripiprazole as a function of AM and AL dose regimens and described the probability of relapse as a function of aripiprazole blood plasma levels. The analysis had a time horizon of 1 year and took the US healthcare payer perspective. The incremental cost per relapse avoided and the probability of cost effectiveness were calculated in deterministic and probabilistic analyses. Scenario analyses explored the model’s main assumptions, and results were validated against external data and other cost-effectiveness analyses. Results Monthly administration of AM 400 mg consistently yielded the lowest predicted number of relapses across deterministic, probabilistic, and scenario analyses. The costs of treatment and relapses were projected to be the lowest with a monthly administration of AL 441 mg. The incremental cost per relapse avoided with AM 400 mg ranged from AM 400 mg being dominant to $US83,300. From willingness-to-pay thresholds of $US30,000 per relapse avoided, the probability of cost effectiveness was highest for AM 400 mg. The validation showed alignment with external data. Conclusion The analysis highlighted the robustness of the novel framework based on pharmacokinetic and pharmacodynamic evidence and demonstrated an application in a postmarketing setting.

Suggested Citation

  • Marjanne A. Piena & Natalie Houwing & Carla W. Kraan & Xiaofeng Wang & Heidi Waters & Ruth A. Duffy & Suresh Mallikaarjun & Craig Bennison, 2022. "An Integrated Pharmacokinetic–Pharmacodynamic–Pharmacoeconomic Modeling Method to Evaluate Treatments for Adults with Schizophrenia," PharmacoEconomics, Springer, vol. 40(1), pages 121-131, January.
  • Handle: RePEc:spr:pharme:v:40:y:2022:i:1:d:10.1007_s40273-021-01077-8
    DOI: 10.1007/s40273-021-01077-8

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    References listed on IDEAS

    1. Meenakshi Srinivasan & Annesha White & Ayyappa Chaturvedula & Valvanera Vozmediano & Stephan Schmidt & Leo Plouffe & La’Marcus T. Wingate, 2020. "Incorporating Pharmacometrics into Pharmacoeconomic Models: Applications from Drug Development," PharmacoEconomics, Springer, vol. 38(10), pages 1031-1042, October.
    2. Andrew H. Briggs & Milton C. Weinstein & Elisabeth A. L. Fenwick & Jonathan Karnon & Mark J. Sculpher & A. David Paltiel, 2012. "Model Parameter Estimation and Uncertainty Analysis," Medical Decision Making, , vol. 32(5), pages 722-732, September.
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