FormalPara Key Points for Decision Makers

Directly rewarding clinical units is more effective in increasing biosimilar uptake than incentivizing an entire hospital structure (hospital administration) as clinicians are deeply engaged.

Previous experience with the experimental incentive may induce a positive spillover effect on prescriber behavior and increase biosimilar penetration for new treatments.

These results support that each initiative targeting biosimilars creates a favorable environment for their prescription, with positive spinoffs, and should therefore be promoted by public policies.

1 Introduction

The loss of patents of blockbuster medicines such as Humira® (adalimumab, AbbVie), which has been the top selling medicine for several years worldwide, and the marketing of several biosimilars promised substantial savings for health care systems. In 2021, biopharmaceuticals accounted for 34% (€78.6 billion) of Europe’s pharmaceutical spending, with €8.8 billion going toward biosimilar medications [1, 2]. As their compound annual growth rate was 10.5% between 2017 and 2021 [1], health care authorities are keen to promote the use of biosimilars, with various policies governing expenditures [3, 4]. Thus, between 2016 and 2020, Spain, Italy, the UK, Germany, and France saved more than €10 billion due to biosimilar use [5].

In France, the interministerial economic committee for health products (CEPS) sets the medicine price for national health insurance (NHI)-covered treatments [3, 6]. Biosimilar prices are set at a 40% discount from the reference product price in the ambulatory care setting (treatment bought by patients in community pharmacies) [3, 7, 8]. First approved as a rheumatoid arthritis treatment, Humira® sales reached US$20 billion worldwide in 2018 and €500 million in France according to IQVIA [9, 10]. Before adalimumab biosimilars were introduced in France, the reference product price (Humira® 40 mg)Footnote 1 was revised from €758.95 (03/2016) to 717.25 (03/2017). It was then reduced concomitantly with the first biosimilar launch to €573.80 in November 2018 (20% discount). The first biosimilar was launched at €430.35 (40% discount).

In parallel with the Humira® patent loss, the French government introduced two new incentives to increase biosimilar use in ambulatory care settings in 2018 because biosimilar natural penetration was found to be limited there (fewer than 10% in the first year of biosimilar launch), despite the pricing difference between original biologic medicines and their biosimilars [12, 13]. These incentives were introduced to encourage the efforts made by clinicians to change their patients’ chronic treatment, as it could take some time. Adalimumab and other biologic medications are mostly prescribed by hospital clinicians (the first prescription must be written by a hospital specialist). Moreover, only clinicians are permitted to switch from one biopharmaceutical to another at this time in France. Substitution by pharmacists has been permitted since April 2022 but is extremely limited (only for filgrastim and pegfilgrastim biosimilars) [11]. Thus, the 2019 NHI annual report predicted a savings of €50 million as a result of the new biosimilar national incentives for hospital prescriptions dispensed in community pharmacies [14].

More precisely, hospitals could enter only one of these incentives, which were mutually exclusive. First, the “general case” redirects 20% of the price difference between the reference product and its biosimilar to hospitals for every biosimilar dispensed in community pharmacies from these hospital prescriptions. It is applicable by default to most French hospitals, those that are under a contractFootnote 2 of quality and efficiency with the French NHI and their Health Regional Agency, and no action was required. Second, the “experimental case” redirects 30% of the price difference between the reference product and its biosimilars directly to clinical units for every biosimilar dispensed in community pharmacies from these clinical units’ prescriptions. The Social Security Funding Act in 2018 authorized this type of national experiment for the testing of new payment schemes such as this alternative profit-sharing scheme [12, 15]. Both incentives were launched a few months apart in 2018 for etanercept and insulin glargine biosimilar groups. Adalimumab was added to these medicines in 2019 after its first biosimilar was introduced (Fig. 1). The adalimumab general case officially started in May 2019 [18]. The adalimumab experiment officially began in April 2019 with the selection of 40 health care hospitals following a call for proposals [13, 16]. The experiment ran for 3 years until the end of 2022 [17]. Both incentives are gainsharing programs financed by the French health care innovation fund. The financing required to implement this incentive was estimated at €9 million per year, and the expected savings provided by the experimental case for adalimumab have been estimated by the French government at €21 million per year [13].

Fig. 1
figure 1

Significant events and study timeline. From 2017 to 2020, the timeline places the study among the other main events that occurred for the adalimumab and etanercept biosimilar groups in France (date of first biosimilar launch, dates of incentives)

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A previous study focusing on the first incentives targeting the etanercept biosimilar group found that the experimental case improved etanercept biosimilar use [19]. This study aimed to confirm the previous one by determining whether the experiment that directly rewards clinical units increases the use of adalimumab biosimilars. Public authorities assumed that physicians would be more engaged the closer the incentive is to them. Furthermore, this research specifically aimed to identify a spillover effect of adalimumab biosimilar with the first experimental case experience. Because the experiment with adalimumab biosimilars was introduced in an additional phase, it compared the adoption of adalimumab biosimilars in hospitals that had previously participated in the etanercept biosimilar incentive experiment and in those that had not, to shed light on spillover effects.

2 Methods

2.1 Study Design

This retrospective observational study focused on the anti-tumor necrosis factor alpha (anti-TNFα) adalimumab group. An analysis of IQVIA Xponent data, a database compiled from a panel of 14,000 community pharmacies (60% of French community pharmacies), allowed us to estimate the number of treatment boxes supplied in community pharmacies linked to the initial hospital prescription (each hospital is identified by the pharmacy in the NHI reimbursement systemFootnote 3) from October 2018 to October 2020 (see the timeline of this study in Fig. 1).

The adalimumab biosimilar group includes the biologic treatment Humira® (reference product, launched in September 2003 in France) and its biosimilars Amgevita® and Imraldi® (both launched in October 2018), Hulio® (launched in February 2019), Hyrimoz® (launched in March 2019), and Idacio® (launched in September 2019). The dispensed product is identified in the dataset by its brand name, the active substance (i.e., adalimumab), and whether it is the reference product or a biosimilar. The quantity of boxes dispensed is weighed according to the number of vials that each box contains and according to the dosage in milligramsFootnote 4 [13].

All hospitals under an experimental case were selected by the public health authorities after a call for proposals, based on the quality of the actions taken on this theme and the quality of the proposed investment model, but also according to the number of patients treated, the target penetration rate of biosimilar within the establishment, and their geographical distribution [20]. Hospitals are identified in the dataset by their FINESS number3, as well as their name, locality (county), type of establishment (public hospitals, teaching and nonteaching, chartered private nonprofit hospitals [that could be private foundations, cancer treatment centers or dialysis centers, etc.], and private for-profit hospitals), and whether or not they are in the experimental case according to the official list published in April 2019 [16]. Hospitals that had previously enrolled in the etanercept experiment were also identified (yes or no). In fact, one of our hypotheses was that their previous experience could have boosted the use of other biosimilars, particularly for adalimumab as another anti-TNFα treatment prescribed by nearly the same clinicians. Their previous enrollment may have increased their awareness of incentives for biosimilar use, and the efforts or organizations made to switch their patients' treatments may have been extended to include adalimumab.

The volume of medicine, surgery, and obstetric (MSO) activity and, in particular, the volume of medicine activity measured for 2018 were added to the data frame using HospiDiag opendata [21]. This term refers to short-term acute activities performed in health facilities, hospitalization (with or without accommodation), or outpatient consultations. It quantifies the annual number of patients dischargedFootnote 5 (see Table 4 in the Appendix [see the electronic supplementary material]), which may reflect the size and the volume of activity of the hospitals. This measure was used to determine whether incentive groups are comparable or if hospitals have a specific profile in the experimental case. From the original dataset, our main analysis focused on hospitals whose prescriptions resulted in at least 30 boxes of adalimumab dispensed in community pharmacies on average by month from November 2017 to October 2018 (before adalimumab biosimilar launch, Fig. 1). The goal of this selection was to maintain as far as possible comparable hospital groups, at least in terms of adalimumab prescription volume, by including hospitals that engage in substantial biologic medicines prescription activity, and because the first observation showed a large disparity of hospitals in the general case group.

2.2 Analyses of Biosimilar Prescription Rates

The analysis was conducted by group of incentive, and carried out in two stages. First, we considered only the incentives to prescribe adalimumab biosimilar in the general case and in the experimental case. Then, subgroups were analyzed according to possible previous experience with the etanercept experiment. The following notation was used to describe groups and subgroups: ADA+ (hospitals in the adalimumab experimental case), ADA− (hospitals in the adalimumab general case), ETA+ (hospitals in the etanercept experimental case), and ETA− (hospitals in the etanercept general case).

Groups and subgroups were described according to selected variables, including geographical repartition, type of establishment, and activity level (global MSO activity and medicine activity). The monthly mean volume of adalimumab boxes dispensed prior to the start of the experiment (from November 2017 to October 2018) and the mean biosimilar rate by group and subgroup (from October 2018 to October 2020) were all calculated. The differences between groups were tested according to the type of variable (chi-square and Fisher’s exact test or average-to-average method) with a 0.05 risk level.

The trends of adalimumab consumption and its biosimilar market share were observed by group of incentive. The monthly mean volume of boxes was calculated globally for all hospitals and by incentive group for this purpose. Then R Studio (V.1.1.453, RStudio Team [2020]) and R program (R Core Team [2016]) [22, 23] were used to compare the distribution of hospitals’ ratesFootnote 6 of biosimilars by month and by incentive group.

The unit of analysis was the hospital (h) for which the monthly (t) rate of biosimilars (BS) was calculated using the following formula, and then results were averaged by subgroups:

$${\text{BS rate}}_{t,h}=\frac{{(\text{total volume of adalimumab BS delivered})}_{h,t}}{({\text{total volume of adalimumab delivered})}_{h,t}}$$

t = the month of dispensation, h = the prescribing hospital

The average rate of biosimilars by incentive (mBSr for “mean biosimilar rate”) was examined for each group to assess the variations in the evolution of biosimilar uptake and determine if the uptake of adalimumab biosimilar was influenced by prior experience with the etanercept experimental case. The search of inflection points on the curves was combined with graph observation to facilitate comparison between subgroups of incentive (see Fig 6 to Fig. 9 in the Appendix [see the electronic supplementary material]).

To assess changes in the overall price and quantity of adalimumab used between 2018–2019 and 2019–2020, all other things being equal, the Laspeyres pricing index and the Paasche quantity index were calculated [24, 25]. Because data are available until October 2020, the volume of adalimumab boxes for biosimilars and the reference product have been extrapolated for 2020.

2.3 Savings

The two incentives were also compared in terms of the budget savings achieved by the French NHI through the use of biosimilars. Considering the following formula for hospitals remuneration (Fig. 2), the savings from the French NHI perspective due to the increase of the biosimilar rate was estimated for the sample. Secondly, a simulation of savings in the general case was calculated using the biosimilar monthly mean rate from the experimental case.

Fig. 2
figure 2

Hospital remuneration formula for a year n according to the French official decrees. NHI national health insurance

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The formula below was used to calculate the savings from NHI perspective from January 2019 to October 2020:

$$\text{NHI savings}=\sum {\text{total volume of adalimumab}}_{t}\times {\text{BSrate}}_{t}\times {\text{price difference}}_{y}$$

t = the month of dispensation, y = the year of dispensation

Price difference between the original product and the biosimilar (BS)

2019

2020

€156.6

€155.2

3 Results

3.1 Adalimumab Biosimilar Uptake by Incentive Group

According to the selection criteria (i.e., minimum volume of adalimumab dispensation from hospital prescriptions), data from the 40 hospitals in the experimental case and from 91 out of the 211 hospitals in the general case were examined from the original dataset. The 120 general case hospitals were removed from the analysis because they were associated with less than 30 boxes of adalimumab dispensed each month.

As shown in Table 1, both groups are geographically well distributed, with the exception of Corse. The experimental group contains far more public teaching hospitals than the general case group. These hospitals are also larger, as illustrated by a higher level of MSO activity, and the majority (70%) of them treat more than 40,400 patients per year (T4 and T5 levels of MSO activity ranges). On the other hand, most of the general case hospitals (55%) treat between 15,000 and 40,000 patients per year (T3 level of MSO activity ranges). The medical activity level appears to be quite similar, with most hospitals having over 20,000 patients yearly (M4 level of activity) in each group. Prior to biosimilar launch, the monthly mean number of adalimumab boxes dispensed from each hospital prescription and the number of hospitals that had previous experience with the experiment (ETA+) were the main differences between each group and were higher in favor of the experimental case.

Table 1 Comparison of the two groups of incentives
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Figure 3 highlights that hospitals in the experimental case had a significantly higher monthly volume of adalimumab prescriptions before the first biosimilar launch (October 2018). Thereafter, the volume of adalimumab dispensations from hospital prescriptions increased over months: from November 2017 to September 2018, 23,200 boxes per month on average were dispensed, and from October 2018 to October 2020, 29,200 boxes per month were dispensed. The distribution remained consistent across groups during the study period, with an average of 62.6% of adalimumab boxes dispensed from hospitals’ prescriptions in the experimental case (minimum 61.3%; maximum 64.2%) (Fig. 3).

Fig. 3
figure 3

Adalimumab market share (monthly global volume of boxes) from November 2017 to October 2020 by hospital group of incentives. The total volume of adalimumab boxes dispensed by community pharmacies is given for the months from November 2017 to October 2020. Each month, the total quantity of adalimumab dispensed comes from prescriptions from hospitals in the experimental case (black bars) and from hospitals in the general case (white bars), which was consistent across months. The black line highlights the adalimumab boxes ratio dispensed from experimental case hospitals prescriptions

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Since adalimumab’s first biosimilar launch, the volume of adalimumab biosimilars has increased quickly, from 280 boxes in November 2018 to more than 10,000 boxes dispensed in October 2020. Between October 2018 and October 2020, the volume of adalimumab biosimilar dispensed from hospital prescriptions increased by 64% in the experimental case and 72% in the general case. Thus, the quantity index increased by +2.1% between 2018 and 2019 and remain constant at −0.2% in 2020. In contrast, the price index decreased by −13.5% in 2019 compared with 2018, and by −1% in 2020 versus 2019. Globally, hospitals in the experimental case accounted for 66% of total of adalimumab biosimilar volume (minimum 62.9%; maximum 87.7%).

The biosimilar rate increased in both groups, but hospitals in the experimental case maintained a higher biosimilar penetration than the general case group (Fig. 4). An upward trend was observed in both cases, but their respective growth rates resulted in a significantly lower biosimilar uptake (p = 0.029) on average throughout the period for general case hospitals (16.7% vs 23.2%) (Table 1). This difference widened over time, reaching mean biosimilar rates of 29.9% and 38.6% in October 2020, respectively. The boxplot also reveals wide variation among hospitals in each group (Fig. 4).

Fig. 4
figure 4

Monthly distribution of the rate of adalimumab biosimilars (BS) by incentive group. Dark boxplots illustrate the distribution of the adalimumab BS rate for hospitals in the experimental case by month from November 2018 to October 2020. Gray boxplots are the same for hospitals in the general case. Their concomitant study allowed us to observe that the mean BS rates by group both increased since the beginning of 2019. The boxplot shows that the difference in the BS rate is more concentrated in the experimental case

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Finally, hospitals in the experimental case were mainly larger public teaching hospitals that induced a higher volume of adalimumab dispensations in community pharmacies and more rapid biosimilar uptake in these dispensations.

3.2 Behaviors of Hospitals with and without Previous Experience with the Experiment

Four subgroups according to the type of incentive (general [ADA−] or experimental [ADA+]) and previous experience with the etanercept biosimilar experiment (“no” [ETA−] or “yes” [ETA+]) were developed. There were 23 hospitals in the experimental case (ADA+) with previous experience with the incentive (ADA+/ETA+ subgroup) and 18 hospitals with no experience (ADA+/ETA−). Among hospitals in the general case (ADA−), ten were in the subgroup with previous experience with this incentive (ADA−/ETA+), and 81 hospitals had never had any experience with the incentive (ADA−/ETA−).

Three of the four subgroups (ADA+/ETA+, ADA+/ETA−, and ADA−/ETA+) were geographically well distributed. They were also similar in terms of establishment type because most of them are public nonteaching hospitals and at least one-third are public teaching hospitals. The activity levels of the three subgroups were comparable and concentrated between 15,000 and 90,000 or more patients treated annually (T3–T5 MSO activity levels). The same was true for the medicine activity (M3–M5 activity levels), with the majority of hospitals (60%) treating 20,000–55,000 patients per year (Table 2). Otherwise, the hospitals in the ADA−/ETA− subgroup were different from one another, with the greatest number of public nonteaching hospitals (82%) and the lowest rate of public teaching hospitals (6%). These hospitals are consequently smaller, with 14% with T0–T2 MSO activity levels and a majority (57%) with T3 MSO activity levels. Moreover, no hospital had an M5 level of medicine activity in this subgroup (Table 2).

Table 2 Comparison of incentive groups with or without previous experience in the experimental case
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Regardless of the adalimumab experimental case subgroup (ADA+/ETA+ and ADA+/ETA−), adalimumab biosimilar uptake in community pharmacy dispensation was identical (mean biosimilar rate of 23%). This uptake has increased in parallel since the first biosimilar launch in October 2018 (Table 2, Fig. 4). ADA+/ETA− hospitals had a higher adalimumab biosimilar uptake than ADA+/ETA+ hospitals in October 2020, but this difference was not significant (40.4% vs 37.3%, p = 0.875).

In contrast, the ADA−/ETA− subgroup had the lowest monthly mean number of adalimumab boxes dispensed from the hospitals’ prescriptions (73 boxes on average vs 262–504 boxes on average for the other subgroups). This group also had a lower rate of biosimilar use (16% on average for the period studied) (Table 2).

There was a difference between general case subgroups in the ADA− group contrary to the experimental case subgroups. However, this difference between ADA−/ETA+ hospitals (mean biosimilar rate of 21%) and ADA−/ETA− hospitals (mean biosimilar rate of 16%) was not statistically significant (p = 0.086).

Figure 5 highlights a comparable trend in the progression of the monthly mean biosimilar rate of each subgroup, with the exception of ADA−/ETA−. They all constantly increased from October 2018 to February 2020 before a downturn. The monthly mean rate of biosimilar growth in the ADA−/ETA− subgroup appeared to be more consistent and slower than that in the other subgroups.

Fig. 5
figure 5

Monthly mean biosimilar rate (mBSr) by incentive subgroup: general (ADA−) or experimental (ADA+) case and prior (ETA+) or no prior (ETA−) experience with the experimental incentive. The mBSr of the two subgroups ADA+/ETA− and ADA+/ETA+ is nearly identical across months. The ADA−/ETA+ subgroup appears to follow the same pattern as the previous two subgroups but with a lower mBSr. The ADA−/ETA− subgroup mBSr appears to be evolving at a much slower rate than the other three groups

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Graphically, we also observed a gap between the three previous subgroups who had experienced the experimental incentive at least once (ADA+/ETA−, ADA+/ETA+, ADA−/ETA+) and the ADA−/ETA− subgroup since the launch of the experimental case in April 2019. However, no significant difference was observed to confirm the greater acceleration (in March 2020, mBSr [SD] 24.1% [14.1%] for the ADA−/ETA− subgroup vs 31.9% [12.4%] for the ADA−/ETA+ subgroup). The ADA+/ETA− and ADA+/ETA+ curves nearly overlap each other, thus a previous experience with ETA seems to not have a significant impact on adalimumab experimental case biosimilar uptake. Otherwise, the curves observations and the inflection points found (see Fig. 6 to Fig. 9 in the Appendix [see the electronic supplementary material]) show a consistent increase of adalimumab biosimilar uptake for all subgroups from the start of the experiment (decree published in April 2019) until a plateau around March 2020 that could indicate a ceiling effect. However, this was also the first coronavirus 2019 (COVID-19) lockdown, between March and May 2020, in France. This event should have paused everything as we observed a clear slowdown of biosimilar uptake in all cases. The fact that the curves did not revert to their pre-March 2020 slope suggests that the probable influence of the COVID-19 crisis was still active in October and November 2020, when a new lockdown was implemented.

Finally, hospitals not under the experimental incentives for adalimumab (ADA−) seemed to be positively influenced by their previous experience with the experimental incentive for etanercept biosimilars that induced a better adalimumab biosimilar uptake. However, this influence appears to be minimal or nonexistent for the hospitals in the experimental case.

3.3 Savings from NHI Perspective

Using adalimumab biosimilars will have saved €8.9 million in the experimental case hospitals and €7.5 million in the general case between January 2019 and October 2020, based on hospital prescriptions of our sample (Table 3). The savings estimates for the NHI were €1.4 million higher in the experimental case, but the mean saved by box was lower for the experimental case than in the general case when compared to the volume of adalimumab dispensed in community pharmacies (Table 3). Otherwise, the simulation with general case hospitals having the same monthly mean biosimilar rate as experimental case hospitals resulted in a €8.5 million savings, compared to €7.5 million with its proper mean biosimilar rate.

Table 3 Adalimumab biosimilar savings estimated in each incentive group from January 2019 to October 2020
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The savings calculated are probably underestimated as we only had access to a sample of community pharmacies, and therefore only a sample of hospitals in the general case, and prescription renewals, which form part of the remuneration calculation, could not be extracted.

4 Discussion

The comparison of the two incentives showed that the experimental case induced better biosimilar uptake than the general case (significant difference p = 0.029, Table 1). As was previously observed in our study focused on etanercept [19], incentives close to prescribers improve biosimilar uptake, indicating that physicians are highly motivated when their efforts are directly recounted.

This study is quite original in that it compared hospitals that had or had not previously experienced the experimental incentive. Whether hospitals are currently ADA+/ETA−, ADA+/ETA+ hospitals, or were previously ADA−/ETA+ hospitals enrolled in the experimental incentive, they all followed the same progression pattern, biasing the main outcomes. Hospitals with prior experimental case experience (ETA+) also had a higher mean biosimilar rate than hospitals that had not been under any experimental incentive either with etanercept or with adalimumab (ADA−/ETA−). Thus, as prescribers’ behavior may have changed to increase etanercept biosimilar prescriptions (i.e., took some measures to convince their patients to switch from the reference product to one biosimilar), they probably applied this previous experience to other biosimilar groups. In fact, etanercept and adalimumab are anti-TNFα medicines, both prescribed by the same physicians in rheumatology (rheumatoid arthritis, ankylosing spondylitis, etc.) and dermatology (psoriasis, etc.). Adalimumab is also prescribed by gastroenterologists for Crohn's disease and ulcerative colitis.

The results also suggested that the adalimumab experimental case group appears to have been less impacted by this prior experience, as seen by the parallel evolution of mean biosimilar uptake of ADA+/ETA− and ADA+/ETA+ hospitals. However, other factors such as the type of hospitals, the volume of their activities, their specific activities, the number of physicians, the administration support, or reaching a glass ceiling in increasing the switch activity, may have an influence.

Scotland had a similar transfer experience with infliximab and etanercept biosimilars. In a study, the result of a previous experience with an etanercept switch plan was shared with prescribers as one of the demand-side measures to increase adalimumab biosimilar uptake [26]. Another study pointed out that the combination of usage-enhancing policies and infliximab biosimilars leads to a higher uptake of biosimilars, using Scotland as an example. The National Health Services (NHS) in Scotland closely monitored the local adoption of biosimilars and highlighted successful switching programs to further improve biosimilars prescription [27]. Moreover, Moorkens et al. (2019) [28] found that etanercept biosimilar uptake was faster than infliximab biosimilar uptake in Sweden, which they hypothesized could be related to past experience with infliximab biosimilars prior to the market launch of etanercept biosimilars. The various case studies of countries with high biosimilar adoption rates highlight a range of health care strategies to support biosimilar adoption, including provider guidance, price policies that are dependent on the health care system, and potential gainsharing arrangements (especially in the UK between clinical commissioning groups and providers, and in Sweden between national and county services, but also with hospitals). The Swedish case notes that the expected savings were not always sufficient to offset the extra workload for providers [28].

The major limitation of this research was the lack of comparability between groups, which is known to be a limit inherent to the evaluation of public policies. There was no randomization between groups, and hospitals in the experimental case were selected based on their motivation (call for proposals). Thus, they should have had a higher interest in biosimilar use because they had the largest market share of adalimumab (superior to 60% in volume, Fig. 3). These hospitals also had a higher activity level (MSO and specifically in medicine) and were more likely to be public teaching hospitals, which are frequently the first ones to use new and innovative treatments. Therefore, they maintain a larger part of the adalimumab biosimilar market share at the end of 2020 and throughout the period of analysis. In addition, the dataset provides only a sample of hospitals included in the general case.

The second main limitation is inherent to the COVID-19 context, which started at the beginning of 2020, particularly with the lockdown in France from March to May 2020. This event should have stopped many clinical units’ activities, to focus on COVID-19 patients, and so could explain the observed slowdown of the adalimumab biosimilar uptake since March 2020.

The difference-in-difference analysis, as we performed in our previous study focused on the etanercept experimental incentive [19], was not possible here because the experimental case and the general case were launched concurrently and very close to the market access of the first biosimilar of adalimumab. Due to the absence of randomization, the uptake of biosimilars may be explained by other unobservable factors (certain hospitals' and patients' characteristics, health care facilities' policies, management support, etc.). Moreover, adalimumab biosimilar uptake could have begun relatively quickly in this scenario as a result of a number of circumstances. The introduction of adalimumab biosimilars may have been anticipated because of the possible cost savings. Hospitals should have been aware of the financial incentives, and their first experience with etanercept could have boosted adalimumab biosimilar penetration. Adalimumab was intended to be added to the general case, as well as the experimental case, which was disclosed earlier before its implementation. Although the decrees were published in April 2019 (experimental case) and May 2019 (general case), the experimental case was announced in February 2019 with the call for proposals, and the general case was already known by the stakeholders. The first hospitals remuneration provided by each incentive was also calculated for all of 2019. Consequently, it was not possible to identify either the natural penetration of adalimumab biosimilars or the effect of each factor.

Finally, the global savings for the French NHI was higher for the experimental case than the general case. The total balance for the NHI, including hospital remuneration, will have to be calculated at the end of the program. The lower the initial biosimilar rate and the higher the biosimilar progression, the greater the total gain. Thus, not all biosimilar groups could be eligible for this type of incentive.

These preliminary descriptive results, which must be confirmed with complete data on all community pharmacy dispensation data and until the end of the experiment (January 2023), shed light on the impact of these incentives. The experience acquired with the experiment must be considered from the perspective of its generalizability.

5 Conclusion

This study confirmed that incentivizing close to prescribers resulted in better biosimilar uptake. This study is also fairly unique in that it suggests hospitals that were previously under the etanercept experimental incentive were more likely to prescribe adalimumab biosimilars even when they were not enrolled in the adalimumab experimental incentive. Thus, prior exposure to the experiment may have a beneficial spillover effect on physician prescribing behavior.

Otherwise, this study is constrained by its descriptive approach and the data collection period that coincided with the COVID-19 epidemic. This research should be continued with the most recent data to confirm the progression of adalimumab biosimilar penetration until the experiment is completed.