How do hospital characteristics and ties relate to the uptake of second-generation biosimilars? A longitudinal analysis of Portuguese NHS hospitals, 2015–2021

Figures & data

Table 1. List of variables.

Variable	Categories	Source
Academic status	Academic Non-academic	Publicly available
Total monthly consumption of biological drugs	High (fourth quartile) Median-Low (quartiles 1–3)^a	Transparency platform of the SNS, by hospital and month
Casemix index	Median-high (quartiles 2–4) Low (first quartile)	Central Administration of the Health System (ACSS), by hospital for the year 2015
Ongoing RCTs	High (fourth quartile) Median-Low (quartiles 1–3)	National Authority of Drugs and Health Products (Infarmed, IP), total for the 2015–2021 period, by hospital
Share of each pharmaceutical firm commercializing reference drugs in the hospital expenditures	High (fourth quartile) Median-Low (quartiles 1–3)	Platform of public contracts (https://www.base.gov.pt/base4), contracts with pharmaceutical firms, by hospital and year.
Rate of overdue debt on total expenditures	High (fourth quartile) Median-Low (quartiles 1–3)	Transparency platform of the SNS, by hospital and year, and ACSS data on total annual expenditures, by hospital and year (2016–2019)

^aFor this variable, the coding was the reverse of the one used for other variables, to avoid a multicollinearity problem.

Figure 1. Biosimilar quota, by year (own construction).

Figure 2. Biosimilar share, by hospital, June 2021* (own construction).*Each bar represents a hospital (its biosimilar share). Adalimumab biosimilar hospital decreasing shares, from 100% to zero %, are used to order shares for other drugs. The x-axis represents the biosimilar share, from 0 to 1 (100%).

Table 2. Median time to adoption and biosimilar quota, by hospital characteristic.

	Median time to adoption					Biosimilar quota (%)
	Adalimumab	Etanercept	Infliximab	Rituximab	Trastuzumab	Adalimumab	Etanercept	Infliximab	Rituximab	Trastuzumab
	22	37	46	46	27	18.0	19.3	54.2	42.1	32.8
Academic hospital
No	23	37	47	46	27	16.9	18.9	56.1	42.0	32.6
Yes	20	36	44	45	26	23.5	21.3	46.0	42.7	33.9
Biologics consumption
Low-median	23	38	44	46	29	16.9	18.2	52.5	42.6	31.2
High	22	34	51	46	23	21.4	22.6	59.3	40.7	38.0
Casemix index
Low	22	38	43	48	28	19.0	19.5	59.0	40.2	31.6
Median-High	22	37	47	45	26	17.6	19.2	53.2	42.5	33.1
Number of RCTs
Low-median	23	38	46	46	28	16.7	17.4	54.1	44.5	31.2
High	21	33	44	46	23	23.2	28.6	54.3	35.8	38.1
Share of originator firm
Low-median	22	37	47	44	27	13.6	15.8	54.9	41.6	31.1
High	22	39	43	46	28	18.8	20.1	50.9	44.3	38.5

Table 3. Hazard ratios of time to biosimilar adoption (standard errors between brackets).

	Adalimumab	Etanercept	Infliximab	Rituximab	Trastuzumab
Academic hospital	1.75 (0.30)***	0.86 (0.09)	1.27 (0.10)***	1.10 (0.11)	1.01 (0.13)
Biologics consumption, high	0.82 (0.12)	1.18 (0.11)*	0.77 (0.06)***	1.03 (0.12)	1.37 (0.15)***
CMI, low	1.08 (0.13)	0.98 (0.08)	1.17 (0.08)**	0.82 (0.09)*	1.06 (0.13)
Number of RCTs, high	0.99 (0.15)	1.35 (0.14)***	1.14 (0.08)*	0.91 (0.09)	1.18 (0.15)
Share originator firm, high	0.89 (0.13)	0.94 (0.08)	1.08 (0.07)	1.16 (0.10)*	1.07 (0.12)
Distribution	Weibull	Gompertz	Weibull	Weibull	Weibull

*10%, **5%, ***1%.

Table 4. Panel data analysis of biosimilar quota (coefficients and standard errors between brackets).

	Adalimumab	Etanercept	Infliximab	Rituximab	Trastuzumab
Time since first adoption (months)	0.17 (0.01)***	0.09 (0.01)***	0.03 (0.01)***	0.11 (0.01)***	0.06 (0.01)***
Academic	0.28 (0.24)	−0.32 (0.28)	−0.10 (0.30)	−0.17 (0.20)	−0.25 (0.28)
Biologics consumption, high (active substance)	−0.53 (0.11)***	−0.14 (0.08)*	−0.24 (0.07)***	0.14 (0.10)	−0.09 (0.10)
CMI, low	−0.04 (0.18)	0.39 (0.19)**	0.15 (0.25)	−0.43 (0.18)**	−0.08 (0.24)
Number of RCTs, high	0.47 (0.22)***	0.78 (0.27)***	0.14 (0.28)	−0.23 (0.19)	0.27 (0.26)
Share originator firm, high	−1.14 (0.19)***	−1.07 (0.20)***	0.05 (0.19)	0.28 (0.16)*	0.39 (0.23)*

*10%, **5%, ***1%.

Table 5. Association of uptake and shares with the burden of overdue debt.

Variable	Uptake	Shares
Adalimumab	6.71 (1.15)***	−0.38 (0.17)**
Etanercept	0.92 (0.08)	−0.37 (0.09)***
Infliximab	0.95 (0.07)	0.02 (0.07)
Rituximab	1.23 (0.12)**	0.34 (0.09)***
Trastuzumab	0.79 (0.12)	−0.07 (0.17)

*10%, **5%, ***1%.

Table 6. Potential savings associated to biosimilars.

Variable	Relative and absolute price difference (biosimilar vs originator drug)	Potential savings (in million euros and in percentage of total expenditures for the drug)
Adalimumab	−24€ (−35%)	20.796 (26%)
Etanercept	−19€ (−13%)	20.439 (7%)
Infliximab	−151€ (−49%)	20.692 (13%)
Rituximab	−4€ (−33%)	0.332 (9%)
Trastuzumab	−170€ (−46%)	12.915 (32%)

Table A1. Test proportional hazard assumption, complete sample

	Etanercept	Rituximab	Trastuzumab
Chi square	20.98	16.36	6.89
p-value	<0.01	0.04	0.55

Table A2. AIC results for various distributions for survival model, complete sample

	Etanercept	Rituximab	Trastuzumab
Gompertz	1,756	334	−276
Weibull	1,850	279	−286
Log-logistic	2,054	374	−310
Log-normal	2,200	337	−327

Table A3. AIC results for various distributions for GEE, complete sample

	Etanercept	Rituximab	Trastuzumab
Normal	1,911,331	3,088,245	1,047,268
Poisson	49,105	32,650	17,586
Negative binomial	10,185	6,932	3,339
Gamma	18,658	15,607	7,741