Budget Impact analysis of a new care system in patients with Parkinson’s disease

Introduction

Parkinson’s disease is a highly prevalent chronic degenerative disease with an extremely variable prevalence rate among the various populations of the world. It has a very significant economic impact from several perspectives: for society, for health systems, for patients and for their families. Worldwide, around 6.2 million people are affected by Parkinson’s disease, but this figure could actually be considerably higher as we know that many people go undiagnosed (1).

A recent nationwide meta-analysis conducted to estimate the prevalence of Parkinson’s disease in Italy showed that there is variability in prevalence rates according to age: 37.8/100,000 inhabitants in the 0-64 age group, 578.7/100,000 in the 65-75 age group and 1,235.7/100,000 in the 75 and over age group (2). The aggregate estimate was 193.7/100,000. Also within the same study, there was an association between the disease and male gender, but only in the older age groups (OR = 1.37, 95% CI 1.22-1.53, and OR = 1.31, 95% CI 1.21-1.42 for age groups 65-74 years and 75 years or older, respectively).

Approximately 1/3 of all patients with “advanced” Parkinson’s disease are not adequately controlled with the usual treatments but require the combination of different classes of treatment including apomorphine, duodopa and deep brain stimulation.

The recent NICE Guidelines indicate the therapy to be followed according to the status of Parkinson’s disease. In particular, for early-stage Parkinson’s disease the choice should be between dopamine agonists, levodopa or monoamine oxidase B (MAO-B) inhibitors for all those patients whose motor symptoms do not impact on their quality of life; for motor symptoms, the choice should be between dopamine agonists, MAO-B inhibitors or COMT inhibitors as an addition to levodopa therapy for all patients who have developed dyskinesias or motor fluctuations. For patients with advanced Parkinson’s disease, deep brain neurostimulation should only be considered when symptoms are not controlled with the best possible pharmacological treatment, which may include subcutaneous apomorphine administered intermittently or by continuous infusion. Apomorphine is also effective on non-motor symptoms (NMS) such as apathy, mood, hallucinations, attention, memory, and gastrointestinal and urinary problems. When “off” periods are associated with intractable pain, apomorphine may be considered an important option to alleviate patients’ discomfort (3).

Continuous treatment with apomorphine is useful in the advanced stages of Parkinson’s disease when oral treatments fail and when apomorphine bolus injections would be too frequent to appropriately manage so many “off” periods during the day. In addition to deep brain stimulation (DBS), apomorphine infusions and duodenal infusions of levodopa-carbidopa (duodopa) represent a concrete therapeutic option (4,5).

Recently, a new apomorphine-based therapy has been developed for the treatment of motor fluctuations (“on-off” phenomena) in patients with Parkinson’s disease who are insufficiently controlled by oral anti-Parkinson’s medication. This therapy, in addition to allowing the new apomorphine dosage in 20 mL (concentration 5 mg/mL) to be administered in a single vial/day (100 mg) to cover the patient’s entire daily requirement, is proposed not only as a new drug but also as a new “treatment system”, as it uses an innovative infusion pump and a “personalised” Patient Support Program (PSP) capable of simplifying the methods of administration and therapy management, resulting in improved compliance and adherence, and thus improved therapeutic results for the patient.

In particular, the PSP provides for:

– the provision of the infusion pump free of charge, as well as information on its management and logistics;

– free supply of all disposable materials (catheters, reservoirs), with guaranteed timely delivery to the patient’s home;

– a series of “homecare” services for the management of the pump and disposable materials for both patient and caregiver;

– in-hospital training courses for nurses, neurologists, patients and caregivers;

– presence of a “free phone number” available to the patient and the caregiver;

– follow-up visits with the nurses involved and calls with the patient;

– questionnaires to assess patient adherence and quality of life.

Although direct comparison studies between apomorphine and levodopa-carbidopa have not yet been conducted, when looking at randomised clinical trials of both infusion therapies, the size of the treatment effect between the two infusions is similar (6,7,8). Compared to patients treated with standard dopamine replacement therapies, levodopa-carbidopa intestinal gel and apomorphine with continuous infusion showed an increase in activation time with no troublesome dyskinesia of 1.9 h (95% CI 0.6-3.2; FU 3 months) (8) and 2.0 h (95% CI 0.7-3.4; FU 3 months) (7), respectively.

Considering the mode of administration, apomorphine infusion is easily reversible and less invasive than levodopa-carbidopa gel as the latter requires the insertion of a gastric tube. The provision of a “personalised” PSP in combination with apomorphine administration would further improve therapy management.

The aim of the study was to assess the economic impacts that could be generated by the introduction of the new apomorphine-based treatment and its PSP service for the treatment of motor fluctuations (“on-off” phenomena) in patients with Parkinson’s disease who are insufficiently controlled by oral anti-Parkinson’s medication.

The economic impact of the launch of the new apomorphine-based treatment on the market will be assessed by comparing the new treatment scenario with the scenario of the treatments currently available on the market.

Methods

The Budget Impact analysis was conducted from the perspective of the Italian National Health Service (NHS) and followed the Guidelines suggested by the International Society of Pharmacoeconomics and Outcome Research (ISPOR) (9,10).

This analysis is based on the comparison of two alternative scenarios: the scenario without the new apomorphine-based treatment, characterised by the presence of the therapies currently available on the market for the treatment of motor fluctuations in patients with Parkinson’s disease (apomorphine hydrochloride 50 mg/5 mL and levodopa + carbidopa 7 bags intestinal gel 100 mL 20 mg/mL + 5 mg/mL), and the scenario in which the introduction of the new therapy on the market is simulated.

The model took into account a time horizon of 3 years of analysis.

Results

Table V shows the estimated direct healthcare costs for each scenario and for each year of analysis as well as the cost difference resulting from the comparison of the two scenarios. For both scenarios, the main expenditure item was characterised by the cost of the drug (98% of total expenditure). The introduction of the new apomorphine-based treatment on the Italian market with increasing shares of patients treated over the years would allow a cumulative reduction in NHS expenditure of more than € 5.7 million over 3 years (Fig. 1). This reduction in expenditure can be attributed to fewer patients being treated with levodopa + carbidopa and to savings in device purchases for patients treated with the new apomorphine-based therapy, as the cost of devices for this treatment is included in the price of the drug.

Looking at the results in each year of analysis, the NHS could achieve a reduction in expenditure of approximately € 676,726 in the first year of analysis, equivalent to over € 1.8 million in the second year of analysis and over € 3.2 million in the third year after the introduction of the new apomorphine-based treatment.

Figure 2 shows that the cumulative Budget Impact value estimated by the economic model is quite robust. In fact, in all scenarios simulated in the deterministic sensitivity analysis, the introduction of the new apomorphine-based treatment results in a cost reduction when compared to the current management of the patients under analysis. In particular, the parameter to which the greatest reduction in expenditure corresponds is the speed of penetration of the new apomorphine-based treatment. By simulating a number of patients treated with the new drug at 75, 195 and 330 in years 1, 2 and 3 respectively, a cumulative saving in NHS expenditure at 3 years of the analysis of approximately € 11.8 million could be achieved. However, it can be seen that in all pessimistic scenarios (MIN), reductions in expenditure would still be achieved.

Figure 3 shows the relationship between the number of patients treated with the new apomorphine-based therapy and the Budget Impact result one year after the introduction of the new apomorphine-based treatment. The analysis shows that the break-even level is 9 patients; therefore, if at least 9 patients on levodopa + carbidopa treatment could be treated, the NHS would begin to incur no additional costs.

Discussion

It is considered that the proposal of a “system of care” that guarantees “personalised” technologies and services (drug + device + PSP), and not just a “single drug”, can respond to still unmet needs of patients (difficulties in correct use and monitoring functions at the service of the patient and facilities), allowing a more correct allocation of available therapeutic resources and a reduction in healthcare costs generated by non-adherence.

Our analysis has four main limitations that must be taken into account. The Budget Impact has been estimated by only taking into account the acquisition and administration costs (in terms of devices and surgery) of the treatments under study, so it is reasonable to assume that this impact represents an underestimation of the real benefits that the introduction of the new treatment could generate in the national context. Furthermore, the analysis was conducted from the perspective of the NHS, which means that indirect costs, which account for more than 30% of the total expenditure associated with Parkinson’s disease, were not taken into account (12,13). A further limitation of the study relates to the estimated number of patients treated with the new apomorphine-based therapy. In fact, it is not easy to understand the real possibility of targeting patients in real clinical practice, but the break-even analysis showed that this percentage is sufficiently low that it does not represent a real barrier to accessing the use of the new apomorphine-based treatment. Finally, the assumption of 100% compliance is an assumption of the simulation model so that the three treatment options under analysis can have the same starting conditions in order to generate a bias-free result. Certainly, considering drug costs alone, compliance would be one variable in decreasing pharmaceutical expenditure; it would also be appropriate to assess the medium- to long-term effects in terms of subsequent management costs. Future and more in-depth analyses could develop this line of research in the field of pharmacoeconomics.

Taking into account the above-mentioned limitations, this analysis showed that the introduction of the new apomorphine-based treatment, including the cost of the device and consumables for continuous infusion, together with a personalised Patient Support Programme, could generate a cumulative reduction in NHS expenditure of more than € 5.7 million within 3 years after its introduction.

Improved patient access would not only allow proper management of Parkinson’s disease sufferers with motor fluctuations (“on-off” phenomena) who are insufficiently controlled by oral anti-Parkinson’s medication, but would also slow the progression of the levodopa + carbidopa treatment line. This would, on the one hand, avoid the need for highly invasive therapies and, on the other hand, reduce pharmaceutical expenditure.

Conclusions

The new apomorphine-based treatment, in combination with a personalised Patient Support Programme system and an innovative continuous infusion system, within the therapeutic options for the treatment of motor fluctuations (“on-off” phenomena) in patients with Parkinson’s disease who are insufficiently controlled by oral anti-Parkinson’s medication, could fill a therapy management gap that is particularly felt by clinicians today and, consequently, generate a reduction in expenditure by the NHS.

Disclosures

Conflict of interest: The Authors declare no conflict of interest.

Financial support: This study was supported by an unconditional grant from Ever Pharma Italia S.r.l.