Aim: Prospective studies support the clinical impact of pharmacogenomics (PGx)-guided prescribing to reduce severe and potentially fatal adverse effects. Drug-gene interactions (DGIs) preventing... Show moreAim: Prospective studies support the clinical impact of pharmacogenomics (PGx)-guided prescribing to reduce severe and potentially fatal adverse effects. Drug-gene interactions (DGIs) preventing potential drug-related deaths have been categorized as "essential" by the Dutch Pharmacogenetics Working Group (DPWG). The collective clinical impact and cost-effectiveness of this sub-set is yet undetermined. Therefore, we aim to assess impact and cost-effectiveness of "essential" PGx tests for prevention of gene-drug-related deaths, when adopted nation-wide. Methods: We used a decision-analytic model to quantify the number and cost per gene-drug-related death prevented, from a 1-year Dutch healthcare perspective. The modelled intervention is a single gene PGx-test for CYP2C19, DPYD, TPMT or UGT1A1 to guide prescribing based on the DPWG recommendations among patients in the Netherlands initiating interacting drugs (clopidogrel, capecitabine, systemic fluorouracil, azathioprine, mercaptopurine, tioguanine or irinotecan). Results: For 148,128 patients initiating one of seven drugs in a given year, costs for PGx-testing, interpretation, and drugs would increase by euro21.4 million. Of these drug initiators, 35,762 (24.1%) would require an alternative dose or drug. PGx-guided prescribing would relatively reduce gene-drug related mortality by 10.6% (range per DGI: 8.1-14.5%) and prevent 419 (0.3% of initiators) deaths a year. Cost-effectiveness is estimated at euro51,000 per prevented gene-drug-related death (range per DGI: euro-752,000-euro633,000). Conclusion: Adoption of PGx-guided prescribing for "essential" DGIs potentially saves the lives of 0.3% of drug initiators, at reasonable costs. Show less
Manson, L.E.N.; Hout, W.B. van den; Guchelaar, H.J. 2022
Human Leukocyte Antigen (HLA) variants can be a risk factor for developing potentially fatal drug hypersensitivity reactions. Our aim was to estimate the potential impact of genotyping for the HLA... Show moreHuman Leukocyte Antigen (HLA) variants can be a risk factor for developing potentially fatal drug hypersensitivity reactions. Our aim was to estimate the potential impact of genotyping for the HLA risk alleles incorporated in the Dutch Pharmacogenetics Working Group (DPWG) guidelines in The Netherlands. We estimated the number of hypersensitivity reactions and associated deaths that can be avoided annually by genotyping for these HLA risk alleles. Additionally, the cost-effectiveness was estimated. Nationwide implementation of genotyping HLA risk alleles before initiating drugs with an actionable drug-gene interaction can potentially save the life of seven allopurinol initiators and two flucloxacillin initiators each year in The Netherlands. Besides these deaths, 28 cases of abacavir hypersensitivity, 24 cases of allopurinol induced SCARs, 6 cases of carbamazepine induced DRESS and 22 cases of flucloxacillin induced DILI can be prevented. Genotyping HLA-B*5701 in abacavir initiators has a number needed to genotype of 31 to prevent one case of abacavir hypersensitivity and is cost-saving. Genotyping HLA-B*5801 in allopurinol initiators has a number needed to genotype of 1149 to prevent one case of SCAR but is still cost-effective. Genotyping before initiating antiepileptic drugs or flucloxacillin is not cost-effective. Our results confirm the need for mandatory testing of HLA-B*5701 in abacavir initiators, as indicated in the drug label, and show genotyping of HLA-B*5801 in allopurinol initiators should be considered. Show less
Birkenhager-Gillesse, E.G.; Achterberg, W.P.; Janus, S.I.M.; Zuidema, S.U.; Hout, W.B. van den 2022
Introduction: We evaluated the cost-effectiveness of the "More at Home with Dementia" intervention, a multicomponent training program for co-residing caregivers of people with dementia (PwDs).... Show moreIntroduction: We evaluated the cost-effectiveness of the "More at Home with Dementia" intervention, a multicomponent training program for co-residing caregivers of people with dementia (PwDs). Methods: We performed a two-armed randomized controlled trial with an intervention and a control group. Participants were community-dwelling caregivers living with a person with dementia (59 randomized to intervention and 50 to control arm). The training program lasted 5 days and took place in a holiday accommodation. Quality-adjusted life-years (QALYs) were calculated using the EuroQol-5 Dimensions 3 Levels (EQ-5D-3L) for caregivers and PwDs. Costs for informal and formal social care, as well as health care, were collected at four times over a 6-month period from baseline. Information on nursing home admission or death was collected for 2 years after baseline. Results: QALYs for caregivers and PwDs added together were 0.12 higher in the intervention group compared with the control group (P = .11). After 1 year, there tended to be fewer nursing home admissions in the intervention group, but this difference was lost by 2 years (P = .19). The cost of the intervention was estimated at euro1000 (USD 1090) per dyad. Compared with the control group, the intervention group used other health care and formal social care significantly less for a year after baseline (P = .02 and .001, respectively). The estimated decrease in total costs was euro10,437 (P = .07), with an estimated 96% probability that the intervention was cost-effective vs usual care. Discussion: The multicomponent "More at Home with Dementia" training program is effective and appears to save costs compared with usual care. Savings appear to be achieved by delaying nursing home admissions and by reducing the use of other care resources. Further research is also needed to clarify if this intervention is effective for caregivers who do not live with a PwD, such as adult children, and for the caregivers of patients with other debilitating chronic diseases. At the same time, effort is advised to implement caregiver training in standard care programs. Show less
Honkoop, P.J.; Loijmans, R.J.B.; Termeer, E.H.; Snoeck-Stroband, J.B.; Hout, W.B. van den; Bakker, M.J.; ... ; Asthma Control Cost-Utility 2015