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Using a genetic, observational study as a strategy to estimate the potential cost-effectiveness of pharmacological CCR5 blockade in dialysis patients

Muntinghe, F. L. H., Vegter, S., Verduijn, M., Boeschoten, E. W., Dekker, F. W., Navis, G. & Postma, M., Jul-2011, In : PHARMACOGENETICS AND GENOMICS. 21, 7, p. 417-425 9 p.

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Background and objective Randomized clinical trials are expensive and time consuming. Therefore, strategies are needed to prioritise tracks for drug development. Genetic association studies may provide such a strategy by considering the differences between genotypes as a proxy for a natural, lifelong, randomized at conception, clinical trial. Previously an association with better survival was found in dialysis patients with systemic inflammation carrying a deletion variant of the CC-chemokine receptor 5 (CCR5). We hypothesized that in an analogous manner, pharmacological CCR5 blockade could protect against inflammation-driven mortality and estimated if such a treatment would be cost-effective.

Methods A genetic screen and treat strategy was modelled using a decision-analytic Markov model, in which patients were screened for the CCR5 deletion 32 polymorphism and those with the wild type and systemic inflammation were treated with pharmacological CCR5 blockers. Kidney transplantation and mortality rates were calculated using patient level data. Extensive sensitivity analyses were performed.

Results The cost-effectiveness of the genetic screen and treat strategy was (sic)18 557 per life year gained and (sic)21 896 per quality-adjusted life years gained. Concordance between the genetic association and pharmacological effectiveness was a main driver of cost-effectiveness. Sensitivity analyses showed that even a modest effectiveness of pharmacological CCR5 blockade would result in a treatment strategy that is good value for money.

Conclusion Pharmacological blockade of the CCR5 receptor in inflamed dialysis patients can be incorporated in a potentially cost-effective screen and treat programme. These findings provide formal rationale for clinical studies. This study illustrates the potential of genetic association studies for drug development, as a source of Mendelian randomized evidence from an observational setting. Pharmacogenetics and Genomics 21: 417-425 (C) 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins.

Original languageEnglish
Pages (from-to)417-425
Number of pages9
JournalPHARMACOGENETICS AND GENOMICS
Volume21
Issue number7
Publication statusPublished - Jul-2011

    Keywords

  • CC-chemokine receptor 5, chemokine-receptor cost-effectiveness, dialysis, Mendelian, polymorphism, STAGE RENAL-DISEASE, GENOMIC SCREENING-PROGRAMS, C-REACTIVE PROTEIN, ECONOMIC EVALUATIONS, MENDELIAN RANDOMIZATION, FUTURE COSTS, HEMODIALYSIS-PATIENTS, UTILITY ANALYSIS, HEALTH, INFLAMMATION

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