Table 11:

Clinical Inputs Used in the Economic Model

Model Parameter	Mean	Distribution	Reference
Prevalence of DPYD Phenotypes
Intermediate metabolizer Poor metabolizer Normal metabolizer	6.60% 0.19% 93.21%	Beta Beta —	Clinical evidence review (pooled prevalence) Clinical evidence review (pooled prevalence) Calculated
Genotype Testing Parameters
Test failure	1.5%	Betaa	Expert opinion
Probability of Overall Severe Toxicity in All Patients
DPYD wild-type DPYD intermediate metabolizer, reduced dose DPYD intermediate metabolizer, standard dose DPYD poor metabolizer, alternative regimen DPYD poor metabolizer, standard dose	13.62% 22.73% 23.53% 13.62% 100%	Beta Beta Beta — —	Lunenburg et al, 20187 Lunenburg et al, 20187 Lunenburg et al, 20187 Assumed to be similar to wild-type Lee et al, 201613; Froehlich et al, 201588; Toffoli et al, 20159; Lee et al, 201458; Boisdron-Celle et al, 200767 (4 compound heterozygous and 2 homozygous carriers received a standard dose; all had severe toxicity)
Probability of Treatment-Related Hospitalization in All Patients
DPYD wild-type DPYD intermediate metabolizer, reduced dose DPYD intermediate metabolizer, standard dose DPYD poor metabolizer, alternative regimen DPYD poor metabolizer, standard dose	7.8% 18.2% 17.6% 7.8% 66.7%	Beta Beta Beta — —	Lunenburg et al, 20187 Lunenburg et al, 20187 Lunenburg et al, 20187 Assume similar to that of wild-type Lee et al, 201613; Froehlich et al, 201513,57; Toffoli et al, 20159,57; Lee et al, 20149,58; Boisdron-Celle et al, 200767 (4 compound heterozygous and 2 homozygous carriers received a standard dose; all had severe toxicity; 4 were fatal); assumed all fatal severity led to hospitalization
Days of Hospitalization for Patients Who Were Hospitalized
DPYD wild-type	13	Normala	Lunenburg et al, 20187
DPYD intermediate metabolizer, reduced dose	4	Normala	Lunenburg et al, 20187
DPYD intermediate metabolizer, standard dose	23	Normala	Lunenburg et al, 20187
DPYD poor metabolizer, alternative regimen	13	Normala	Assumed to be similar to that of wild-type
DPYD poor metabolizer, standard dose	29	Normala	Assume 25% longer than that of intermediate metabolizer
Probability of Death Among Patients With Severe Toxicities
DPYD wild-type	1.3%	Beta	Henricks et al, 201872
DPYD intermediate metabolizer, reduced dose	1.3%	—	Assume similar to that of wild-type
DPYD intermediate metabolizer, standard dose	14.3%	Beta	Deenen et al, 201673
DPYD poor metabolizer, alternative regimen	1.3%	—	Assumed to be similar to that of wild-type
DPYD poor metabolizer, standard dose	66.7%	Beta	Lee et al, 201613; Froehlich et al, 201588; Toffoli et al, 20159; Lee et al, 201458; Boisdron-Celle et al, 200767 (4 compound heterozygous and 2 homozygous carriers received a standard dose; all had severe toxicity; 4 were fatal)
Average Number of Severe Toxicities per Patient Who Had Severe Toxicity
DPYD wild-type	1.5b	Normala	Lunenburg et al, 20187
DPYD intermediate metabolizer, reduced dose	1.4b	Normala	Lunenburg et al, 20187
DPYD intermediate metabolizer, standard dose	2.1b	Normala	Lunenburg et al, 20187
DPYD poor metabolizer, alternative regimen	1.5	—	Assumed to be similar to that of wild-type
DPYD poor metabolizer, standard dose	2.1	—	Assumed to be similar to that of intermediate metabolizers

^aAssumed standard error to be 20% of mean.

^bDerived by dividing the total number of adverse events reported (which were broken down by type of adverse event) by the number of patients who experienced an adverse event.