COMUNICACIÓN BREVE

 

Factor VIII delivery devices in haemophilia A. Barriers and drivers for treatment adherence

Dispositivos de administración de Factor VIII en la hemofilia A. Barreras y estímulos para la adherencia

 

 

Isabel Fernández-Arias and Hae Kyung Kim

Unidad Médica, Pfizer S.L.U.

This project has been funded by Pfizer. Its authors are employees of Pfizer, S.L.U.

Correspondence

 

 

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ABSTRACT

Introduction and objective: To capture the experience of haemophilia A patients with their devices for coagulation factor reconstitution, the barriers for treatment adherence; and to determine their preferences, presenting a new double-chamber syringe (DCS).
Method: A cross-sectional research through a supervised survey and a DCS testing session.
Results: Seventy-four (74) patients participated, 50% of them on prophylaxis treatment, and 7 years (median) with their usual treatment (IQR 17.25). In the survey, the DCS received the highest score (75/100, p < 0.001) and it was the most likely to be used in prophylactic treatment (p < 0.001). In the practical testing session (n = 29), 62.1% preferred the DCS, and required 43 seconds as median time (24.5-82) for preparation, vs. 4 minutes (1-15) with their usual treatment (p < 0.001). The favourable opinion of their doctor regarding prophylaxis was very influential on the attitude of participants towards treatment adherence (OR = 1.324, CI 95% = 1.040-1.685, p = 0.023).
Conclusions: The DCS was the preferred device, and was likely to encourage prophylaxis.

Key words: Haemophilia A; Factor VIII; Prophylaxis; Drug Delivery Systems; Medication Adherence.

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RESUMEN

Introducción y objetivo: Recabar la experiencia de pacientes con hemofilia A con sus dispositivos de reconstitución de factor de coagulación, barreras para la adherencia y determinar sus preferencias, presentando una nueva jeringa de doble cámara (JDC).
Método: Investigación transversal mediante encuesta dirigida y sesión de prueba de la JDC.
Resultados: Participaron 74 pacientes, el 50% en tratamiento con profilaxis, y 7 años (mediana) con su tratamiento habitual (RIC 17,25). En la encuesta, la JDC recibió la mayor puntuación (75/100, p < 0,001) y la mayor probabilidad de uso en profilaxis (p < 0,001). En la sesión práctica (n = 29), el 62,1% prefirió la JDC y necesitaron de mediana 43 segundos (24,5-82) para la preparación, vs. 4 minutos (1-15) con el tratamiento habitual (p < 0,001). La opinión favorable del médico respecto a la profilaxis resultó muy influyente en la actitud de los participantes hacia la adherencia (OR = 1,324, IC 95% = 1,040-1,685, p = 0,023).
Conclusiones: La JDC fue el dispositivo preferido y se mostró con probabilidad de favorecer la profilaxis.

Palabras clave: Hemofilia A; Factor VIII; Profilaxis; Sistemas de administración; Adherencia a la medicación.

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Contribution to Scientific Literature

The self-administration of intravenous Factor VIII by haemophilia patients requires spending some time for preparing and infusing the factor. The different coagulation factors available in the market present a variety of devices. The objective of this study was to determine the barriers perceived, and the opinions of adults with Haemophilia A regarding their treatment and prophylaxis, as well as their preference among those devices currently available in the market.

 

Introduction

There are around 2,000 persons with haemophilia A (HA) in Spain^1,2, and 60% of them are on a Factor VIII (FVIII) replacement therapy through intravenous infusion, either on prophylactic or on-demand treatment³; prophylactic treatment presents higher efficacy in the prevention of spontaneous haemorrhages³. Treatment efficacy is partly determined by the level of adherence^4,5 and patient motivations^5,6, as well as by their opinions and expectations about their disease and treatment^4-8. Besides, it is worth highlighting the potential influence presented by the difficulties that can be associated with the treatment^5,8, its convenience of use and time of preparation^4-6. A device has been recently designed, consisting of one single syringe with two chambers containing the freeze-dried recombinant FVIII, and the solvent for its reconstitution. This article collects the experience and opinions of Spanish adult patients with HA regarding their treatment and the double-chamber syringe (DCS), as well as the factors that have an impact on their patterns of use, and the potential barriers for treatment adherence. A subgroup of patients took part in a practical testing session, and completed an opinion survey after conducting all steps for factor reconstitution with the DCS (FuseNGo^®, Pfizer S.L.U., Madrid).

 

Methods

This cross-sectional research was conducted in five countries (Germany, Austria, Spain, Italy and United Kingdom)⁹, and this article presents the outcomes for Spain. This is an opinion survey, and therefore required no evaluation by an Ethics Committee. The survey was conducted according to the principles of the Declaration of Helsinki and the Organic Law for Data Protection, and all participants granted their written consent.

The study included 18-to-65-year old men with HA who were using routinely a FVIII replacement therapy (prophylactic or on-demand), and who had used their current treatment on ≥ 20 occasions. The survey excluded all those who had any association with the pharmaceutical or healthcare industry or with market research or advertising companies, or regulatory authorities.

Procedure

The participants, recruited through 4 patients associations, completed a questionnaire about their experience and preferences with existing devices¹⁰ (Appendix 1). Their preference was explored regarding five devices described through drawings but not identified (Figure 1), including the DCS.

A subgroup of patients also took part in a testing session for the DCS, where its functioning was explained. Each participant was given a device without needle and with placebo components (powder and solvent). The time required for reconstitution was measured in four repeat tests, and the participants completed a questionnaire about device use and preference.

In order to determine any barriers for treatment adherence, the participants answered questions based on the principles of the Theory of Planned Behaviour¹¹ (Appendix 1).

Statistical Analysis

A descriptive statistical analysis was conducted for the survey answers, and univariate and multivariate analysis in order to identify the factors associated with treatment adherence. Data were analyzed with SPSS version 19.0.

 

Results

In Spain, 74 patients were recruited (73% < 40-year-old). Out of these, 50% were on prophylactic treatment (median of 3 times/ week, interquartile range [IQR] = 1); the clotting factors used and the treatment regimen are described in figure 2. The median time with their current treatment was 7 years (IQR = 17.25).

The participants expressed moderate satisfaction (median 4-6/10) with their current treatment regarding ease and time of preparation, storage, and disposal of used materials; efficacy was the best valued characteristic (median 8). From the 5 devices suggested (Figure 1), No. 5 (the DCS) received significantly superior scores vs. the others (Figure 3A). Besides, they stated that they would choose the DCS for use in prophylactic treatment over the others (Figure 3B), even increasing the frequency of administration (Figure 3C).

In the testing session (n = 29), the participants needed 43 seconds as median time (24.5-82.0, IQR = 14.75 s) for factor reconstitution with the DCS, and this time was significantly reduced with practice (p < 0.001), and was significantly lower than the time required with their usual device (median 4 min; range = 1-15, IQR = 3.75 min). A 62.1% (n = 18) of patients preferred the DCS, and 24.1% (n = 7) preferred their current device.

Finally, the experience of living with haemophilia was assessed, including factors associated with treatment adherence. The conclusion was that self-treatment was not a problem, but some patients were afraid of the transmission of infectious diseases (median 6), or the contamination of the factor during preparation (median 5). For patients on prophylactic treatment, the opinions of their partner (100%) and their doctor (81.1%) appeared as independent factors encouraging treatment adherence. In a multivariate logistical regression analysis, only the opinion by the doctor remained as a factor associated to prophylactic treatment adherence (OR = 1,324; CI 95% = 1.040-1.685; p = 0,023).

 

Discussion

Prophylactic treatment is currently established as the most adequate therapeutic approach³, but treatment adherence represents a complex matter, including several factors such as patient expectations, time required, and satisfaction, among others^3,5-8,12. Therefore, it is interesting to determine if facilitating the task for patients with haemophilia would represent any change in their habits, as well as to explore the reasons that lead them to choose their treatment regimen. Accordingly, this survey explored the practical experience and uptake of a device specifically designed to simplify factor reconstitution with safety, and to reduce the time required for administration.

Participants claimed that they were moderately satisfied with their current treatment, and efficacy was the best valued aspect. However, times of preparation and administration were relatively long. Compared with other devices currently available, the DCS was the preferred method, both by patients on prophylactic and on-demand treatment. This outcome was in line with the overall international research⁹, though the scores of Spanish patients for some devices (including the DCS) were slightly lower to the median of the international analysis⁹. A higher proportion vs. the international analysis stated that they preferred the DCS (62.5% vs. 57.1%)⁹, but the proportion of patients satisfied with their current treatment was also superior (25.5% vs. 24.1%)⁹. It is important to point out that surveys in Spain were conducted in a neutral setting (headquarters of patients associations), while in some other countries, participants answered questions by the professionals who were managing them regularly, which could have had an impact on some of their answers. It stands out that the DCS was described as the system with a higher likelihood of directing patterns of use towards prophylaxis, even if this required an increase in the administration frequency. The favourable opinion about these two aspects was also superior to the international median⁹. It appears interesting that the type of device can encourage prophylaxis among patients with HA^4,13 and favour an adequate frequency of use to maintain the concentration of FVIII in blood (up to once a day, according to some studies¹⁴). In any case, surveys disclosed that the influence of third parties (such as their partner or doctor) is an important factor regarding patient habits. In this sense, treatment patterns and adherence would be driven particularly by the opinion of their doctor, which is consistent with studies establishing the importance of a good relationship with the treating doctor for success in prophylaxis¹⁵.

The limitations of this research are associated with methodology. Patients were recruited through their associations, and therefore there was a random incorporation, and data were only obtained from the surveys of those who decided to take part. The face-to-face sessions in Spain were conducted by researchers not linked to the participating centres; therefore, answering questions asked by an unknown person could have had some influence on their answers, though this would have been minimal. It would have been appropriate to conduct a simultaneous test of preparation times with other devices; but, in any case, participants were required to have used their usual treatment at least 20 times, and therefore their experience offered consistency to their answers. On the other hand, the lack of previous experience with the DCS at the time of testing must be taken into account, in comparison with their usual device.

In conclusion, patients value positively the fact that their treatment is easy and fast, and they state that these aspects could lead them to favour prophylactic treatment and good treatment adherence. The satisfaction or ease of use of their treatment devices can have an influence, but the opinion of their doctor is also important at the time of following prophylactic treatment. The outcomes of this survey indicate that the DCS could favour treatment adherence among patients with HA, and reduce their negative perceptions about the commitment that could be caused by prophylactic treatment in those patients switching from an on-demand treatment.

 

Acknowledgements

The authors wish to thank the following patients' associations for their collaboration in this research: Galician Association of Haemophilia (AGADHEMO), Haemophilia Association of the Community of Madrid (ASHEMA-DRID), Haemophilia Association of the Community of Valencia (ASHECOVA) and Andalusian Association of Haemophilia (ASANHEMO).

 

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Correspondence:
Correo electrónico: lsabel.fernandez-arias@pfizer.com
(Isabel Fernández Arias).

Recibido el 11 de febrero de 2016;
aceptado el 18 de agosto de 2016.