Pharmacoeconomic advantages of subcutaneous versus intravenous immunoglobulin treatment in a Canadian pediatric center
2012; Elsevier BV; Volume: 131; Issue: 2 Linguagem: Inglês
10.1016/j.jaci.2012.08.022
ISSN1097-6825
AutoresThiérry Ducruet, Marie-Claude Levasseur, Anne Des Roches, Ayman Kafal, Renée Dicaire, Élie Haddad,
Tópico(s)Chronic Lymphocytic Leukemia Research
ResumoAlthough the data in the literature indicate that both subcutaneous (SC) and intravenous (IV) routes of administration of immunoglobulin (SC-Ig and IV-Ig) therapy are considered equivalent in terms of efficacy for patients with primary immunodeficiency,1Chapel H.M. Spickett G.P. Ericson D. Engl W. Eibl M.M. Bjorkander J. The comparison of the efficacy and safety of intravenous versus subcutaneous immunoglobulin replacement therapy.J Clin Immunol. 2000; 20: 94-100Crossref PubMed Scopus (271) Google Scholar, 2Gardulf A. Nicolay U. Asensio O. Bernatowska E. Bock A. Carvalho B.C. et al.Rapid subcutaneous IgG replacement therapy is effective and safe in children and adults with primary immunodeficiencies–a prospective, multi-national study.J Clin Immunol. 2006; 26: 177-185Crossref PubMed Scopus (166) Google Scholar, 3Ochs H.D. Gupta S. Kiessling P. Nicolay U. Berger M. Safety and efficacy of self-administered subcutaneous immunoglobulin in patients with primary immunodeficiency diseases.J Clin Immunol. 2006; 26: 265-273Crossref PubMed Scopus (210) Google Scholar the question of the cost effect of this treatment remains an important economics question. Some pharmacoeconomic studies that compared SC-Ig with IV-Ig therapy have been performed in various countries,4Beaute J. Levy P. Millet V. Debre M. Dudoit Y. Le Mignot L. et al.Economic evaluation of immunoglobulin replacement in patients with primary antibody deficiencies.Clin Exp Immunol. 2010; 160: 240-245Crossref PubMed Scopus (58) Google Scholar, 5Gardulf A. Andersen V. Bjorkander J. Ericson D. Froland S.S. Gustafson R. et al.Subcutaneous immunoglobulin replacement in patients with primary antibody deficiencies: safety and costs.Lancet. 1995; 345: 365-369Abstract Full Text PDF PubMed Scopus (266) Google Scholar, 6Hogy B. Keinecke H.O. Borte M. Pharmacoeconomic evaluation of immunoglobulin treatment in patients with antibody deficiencies from the perspective of the German statutory health insurance.Eur J Health Econ. 2005; 6: 24-29Crossref PubMed Scopus (75) Google Scholar but their conclusions were not unequivocal, and, as reviewed by Membe et al,7Membe S.K. Ho C. Cimon K. Morrison A. Kanani A. Roifman C.M. Economic assessment of different modalities of immunoglobulin replacement therapy.Immunol Allergy Clin North Am. 2008; 28 (x): 861-874Abstract Full Text Full Text PDF PubMed Scopus (35) Google Scholar those studies could not be transposed to the Canadian or US health system.In 2007, when the Quebec government approved the use of SC-Ig, we offered our patients the choice between hospital-based IV-Ig and home-based SC-Ig, administered at equivalent doses. Most patients decided to switch to SC-Ig, allowing us to perform a retrospective pharmacoeconomic cohort study of 25 patients, in which we calculated expenditures for IV-Ig and then SC-Ig therapy over 2 consecutive years in the same cohort. Patients were eligible if they had been diagnosed with a primary immunodeficiency8Notarangelo L.D. Fischer A. Geha R.S. Casanova J.L. Chapel H. Conley M.E. et al.Primary immunodeficiencies: 2009 update.J Allergy Clin Immunol. 2009; 124: 1161-1178Abstract Full Text Full Text PDF PubMed Scopus (384) Google Scholar and received at least 1 year of uninterrupted IV-Ig before at least 1 year of uninterrupted SC-Ig. Because the literature clearly reported that both routes of administration were equivalent in terms of efficacy and safety,1Chapel H.M. Spickett G.P. Ericson D. Engl W. Eibl M.M. Bjorkander J. The comparison of the efficacy and safety of intravenous versus subcutaneous immunoglobulin replacement therapy.J Clin Immunol. 2000; 20: 94-100Crossref PubMed Scopus (271) Google Scholar, 2Gardulf A. Nicolay U. Asensio O. Bernatowska E. Bock A. Carvalho B.C. et al.Rapid subcutaneous IgG replacement therapy is effective and safe in children and adults with primary immunodeficiencies–a prospective, multi-national study.J Clin Immunol. 2006; 26: 177-185Crossref PubMed Scopus (166) Google Scholar, 3Ochs H.D. Gupta S. Kiessling P. Nicolay U. Berger M. Safety and efficacy of self-administered subcutaneous immunoglobulin in patients with primary immunodeficiency diseases.J Clin Immunol. 2006; 26: 265-273Crossref PubMed Scopus (210) Google Scholar a cost-minimization analysis was applied. Methods and allocation of unit costs for resource valuation from various sources are shown in Table E1 (see this article's Online Repository at www.jacionline.org) and patient characteristics in Table E2 (see this article's Online Repository at www.jacionline.org).As shown in Table I, the time spent by parents in taking care of their children's treatment was significantly greater for IV-Ig than for SC-Ig. In addition, estimated time spent by nurses, technicians, and administrative assistants was higher for patients treated with IV-Ig. We found that the cost of medical resources and the cost of nonmedical resources were both significantly lower when patients were treated with SC-Ig (P < .001 and P < .001, respectively; Table II). In addition, the total cost (medical plus nonmedical costs) associated with SC-Ig was significantly lower than that associated with IV-Ig ($6.488 ± $4.571 vs $10,761 ± $7,874 per patient per year; P < .001, respectively; Table II). In this calculation, the cost of immunoglobulins was not taken into consideration, although they were quite similar for the different groups. Indeed, in Quebec (and in the rest of Canada), there is parity in the price per gram of SC-Ig and IV-Ig. The cost of immunoglobulins by itself accounted for about 48% and 66% of the total cost of IV-Ig and SC-Ig therapy, respectively. Interestingly, the total expenditures, which include the cost of immunoglobulins, were still significantly higher for the IV-Ig than for the SC-Ig route ($23,845 ± $13,245 vs $19,044 ± $9,476 per patient per year; P < .001, respectively) despite this high proportion of cost for immunoglobulins.Table IAssessment of time per year and per patient spent by parents and care providers according to treatmentIV, mean ± SDSC, mean ± SDSC-Ig minus IV-Ig, mean (95% CI)P value (signed rank test)Time (h) spent by parents (treatment supervision and administration and time spent in hospital visits)160 ± 10578 ± 40−82 (−123 to −40)<.001Nurse (h)607.5−52.5Technician (h)31−2Administrative assistant (h)31 1/3−1 2/3 Open table in a new tab Table IIMedical and nonmedical resource use and costs over the first year by dollars per patientIV, mean ± SDSC, mean ± SDSC-Ig minus IV-Ig, mean (95% CI)P value (signed rank test)Nonmedical resources (1) Travel expensesTransports (taxi, bus, metro, own car)773 ± 921193 ± 230−580 (−865 to −295)Hotel182 ± 47646 ± 119−137 (−284 to 11)Parking63 ± 7316 ± 18−48 (−70 to −25)Total1,019 ± 1,222255 ± 305−764 (−1,142 to −386)<.001 (2) Time spent by parents (treatment supervision and administration and time-spent in hospital visits)3,687 ± 2,4301,807 ± 935−1,880 (−2,840 to −920)<.001 (3) Other resources (Emla cream)<169 ± 12669 (17 to 121).03 Total nonmedical resources (1) + (2) + (3)4,706 ± 3,1092,131 ± 976−2,575 (−3,773 to −1,378)<.001Medical resources (4) Nurse, technician, administration (SJH)1,867273−1,594 (5) Pump, infusion materials136780644 (6) Medical services (consultations)2,685 ± 5,5081,918 ± 2,882−767 (−2,853 to 1,318).14 (7) Pharmaceuticals1,367 ± 3,6301,387 ± 3,16420 (−1,024 to 1,063).81 Total medical resources (4) + (5) + (6) + (7)6,055 ± 6,1974,358 ± 4,495−1,698 (−3,242 to −153)<.001 Total medical and nonmedical resources10,761 ± 7,8746,488 ± 4,571−4,273 (−6,215 to −2,331)<.001Immunoglobulins13,084 ± 9,22512,556 ± 8,046−528 (−1,716 to 660).36Total medical and nonmedical resources + immunoglobulins23,845 ± 13,24519,044 ± 9,476−4,801 (−7,419 to −2,183)<.001Cost according to perspective Patient perspective (1) + (2) + (3) + (5) (only for SC)4,706 ± 3,1092,911 ± 977−1,795 (−2,993 to −598).05∗Four patients had to stay overnight in Montreal, and, when these patients were removed, the P value from the patient's perspective (SC vs IV) was not significant anymore (Δ = −$345, P = .24). However, the total medical and nonmedical resources without or with immunoglobulins were still significant, P = .011 and .021, respectively. Government perspective (4) + (5) (only for IV) + (6) + (7)6,055 ± 6,1973,578 ± 4,495−2,478 (−4,022 to −933).003SJH, Ste-Justine Hospital.∗ Four patients had to stay overnight in Montreal, and, when these patients were removed, the P value from the patient's perspective (SC vs IV) was not significant anymore (Δ = −$345, P = .24). However, the total medical and nonmedical resources without or with immunoglobulins were still significant, P = .011 and .021, respectively. Open table in a new tab With respect to certain purchases such as pumps and infusion material that were covered by the hospital for IV-Ig and by the patients for SC-Ig, we adjusted our calculations for both a patient/parent perspective and a government/hospital one and found, as shown in Table II, that, all in all, the SC route remained less costly than the IV route from either the patient perspective (P < .001) or the government perspective (P < .001).We then performed a secondary analysis (sensitivity analysis) in which we considered only the loss of productivity for parents (ie, the number of hours parents declared to have spent away from their work to take care of their child), whereas for nurses we considered an estimated time that was based on an increased caseload of 5 patients per nurse instead of 2. On this basis, the total cost (medical plus nonmedical costs) was still significantly lower, as shown in Table E3 (see the Online Repository at www.jacionline.org), for SC-Ig compared with IV-Ig without or with including the cost of immunoglobulins (P < .001 and P = .03, respectively), thereby indicating that even considering this worst-case scenario (secondary analysis), the cost of SC-Ig therapy was significantly lower than that of IV-Ig therapy.From a patients perspective with the use of this secondary analysis as described, costs for patients were still less for SC-Ig than for IV-Ig, although statistical significance was not reached (P = .23), whereas from a government perspective, costs were still significantly less for SC-Ig than for IV-Ig (P < .001), even if the cost of immunoglobulins was taken into account (P = .03; see Table E3 in this article's Online Repository at www.jacionline.org).Interestingly, for the true cost of medications and medical consultations, no significant difference was observed between the 2 treatment groups (Table II). Expenditures related to the use of physicians were higher, although not statistically significant, for IV-Ig compared with SC-Ig, probably because patients treated with IV-Ig were charged for each monthly visit as opposed to every 4 to 6 months for those receiving SC-Ig. Costs for medications, which essentially comprised antibiotics, were similar for the 2 groups (Table II), suggesting that switching from IV-Ig to SC-Ig did not result in a higher number of infections. Moreover, the number of hospitalizations was similar for the 2 groups (data not shown).This retrospective study was performed within a single university-based hospital, which is less desirable than a prospective case–control study. However, by using each case as its own control provided considerable advantages, such as limiting selection bias, thereby making the 2 groups most comparable and also by eliminating inter-individual variability. Notwithstanding the small study sample size (n = 25), we found a statistically significant decrease, even in the secondary analysis, in both medical and nonmedical costs associated with switching from a hospital-based IV-Ig regime to that of a home-based SC-Ig regime. Furthermore, the results were consistent across the different payer perspectives whether it was the patient, the hospital, or the government. This is one of the first studies to address and encompass all of these various aspects. Another strong point is that most of our information was gathered from official, exhaustive, and computerized government sources, which minimized the need for cost estimates. Moreover, unlike other pharmacoeconomic studies,4Beaute J. Levy P. Millet V. Debre M. Dudoit Y. Le Mignot L. et al.Economic evaluation of immunoglobulin replacement in patients with primary antibody deficiencies.Clin Exp Immunol. 2010; 160: 240-245Crossref PubMed Scopus (58) Google Scholar, 5Gardulf A. Andersen V. Bjorkander J. Ericson D. Froland S.S. Gustafson R. et al.Subcutaneous immunoglobulin replacement in patients with primary antibody deficiencies: safety and costs.Lancet. 1995; 345: 365-369Abstract Full Text PDF PubMed Scopus (266) Google Scholar, 6Hogy B. Keinecke H.O. Borte M. Pharmacoeconomic evaluation of immunoglobulin treatment in patients with antibody deficiencies from the perspective of the German statutory health insurance.Eur J Health Econ. 2005; 6: 24-29Crossref PubMed Scopus (75) Google Scholar we observed that the cost differential was not related to any difference in the price of immunoglobulins, and, even when the price of immunoglobulins was not taken into account, the cost associated with SC-Ig treatment was significantly lower, suggesting that the observed differences were related to the other pharmacoeconomic factors.Importantly, none of our patients had any desire to switch back to hospital-based IV-Ig therapy (patients were questioned about this issue at every visit). Studies have found that treatment at home provides patients and their families with a better quality of life as related to several aspects, including treatment independence and convenience, mental health, school and social functioning, and family activities.9Gardulf A. Nicolay U. Math D. Asensio O. Bernatowska E. Bock A. et al.Children and adults with primary antibody deficiencies gain quality of life by subcutaneous IgG self-infusions at home.J Allergy Clin Immunol. 2004; 114: 936-942Abstract Full Text Full Text PDF PubMed Scopus (218) Google Scholar, 10Nicolay U. Kiessling P. Berger M. Gupta S. Yel L. Roifman C.M. et al.Health-related quality of life and treatment satisfaction in North American patients with primary immunedeficiency diseases receiving subcutaneous IgG self-infusions at home.J Clin Immunol. 2006; 26: 65-72Crossref PubMed Scopus (164) Google Scholar Thus, once patients switch from IV-Ig to SC-Ig, they are unlikely to switch back; hence, the pharmacoeconomic effect would be for the long term.Given that both treatment options are equally effective and safe,1Chapel H.M. Spickett G.P. Ericson D. Engl W. Eibl M.M. Bjorkander J. The comparison of the efficacy and safety of intravenous versus subcutaneous immunoglobulin replacement therapy.J Clin Immunol. 2000; 20: 94-100Crossref PubMed Scopus (271) Google Scholar, 2Gardulf A. Nicolay U. Asensio O. Bernatowska E. Bock A. Carvalho B.C. et al.Rapid subcutaneous IgG replacement therapy is effective and safe in children and adults with primary immunodeficiencies–a prospective, multi-national study.J Clin Immunol. 2006; 26: 177-185Crossref PubMed Scopus (166) Google Scholar, 3Ochs H.D. Gupta S. Kiessling P. Nicolay U. Berger M. Safety and efficacy of self-administered subcutaneous immunoglobulin in patients with primary immunodeficiency diseases.J Clin Immunol. 2006; 26: 265-273Crossref PubMed Scopus (210) Google Scholar the financial arguments for SC-Ig are appealing with greater expected benefits at less cost. This is particularly relevant in Quebec where the study was performed but could easily be applicable to most health care systems in the Western world. In several societies, most medical expenses are covered or reimbursed by the government, whereas in others the same expenses would be handled by private insurance or the individual directly. Our data show that, no matter what the circumstances, there are appreciable economic incentives in favor of home-based SC-Ig treatment.As stated in our study, the dose of SC-Ig was equivalent to the dose of IV-Ig, as is done in Europe,11Jolles S. Bernatowska E. de Gracia J. Borte M. Cristea V. Peter H.H. et al.Efficacy and safety of Hizentra((R)) in patients with primary immunodeficiency after a dose-equivalent switch from intravenous or subcutaneous replacement therapy.Clin Immunol. 2011; 141: 90-102Crossref PubMed Scopus (92) Google Scholar whereas US recommendations lean toward a 37% higher dose of SC-Ig.12Hagan J.B. Fasano M.B. Spector S. Wasserman R.L. Melamed I. Rojavin M.A. et al.Efficacy and safety of a new 20% immunoglobulin preparation for subcutaneous administration, IgPro20, in patients with primary immunodeficiency.J Clin Immunol. 2010; 30: 734-745Crossref PubMed Scopus (104) Google Scholar If the latter dosage had been used, it would have led to a 37% increase in the cost of immunoglobulins for the SC-Ig group, which in our model would have resulted in the matching of total expenditures for both treatments. The savings from other medical and nonmedical expenses, in turn, would still have offset this, as we have shown. This is especially relevant because the price of the product itself, which constitutes the bulk of the cost, is likely to change in the future. The benefits from the patient's perspective would also remain, facilitating their tolerability of the treatment and easing the burden for families, which in terms of macroeconomics and health care policies are still of the outmost importance.With the current efforts to improve efficiency in health care delivery and resource management, this type of pharmacoeconomic study could become an example of how to realistically transform a costly therapy for a chronic illness into a more economical and patient-oriented alternative, especially considering the lasting monetary effect on the health care system, which should be substantial. Although the data in the literature indicate that both subcutaneous (SC) and intravenous (IV) routes of administration of immunoglobulin (SC-Ig and IV-Ig) therapy are considered equivalent in terms of efficacy for patients with primary immunodeficiency,1Chapel H.M. Spickett G.P. Ericson D. Engl W. Eibl M.M. Bjorkander J. The comparison of the efficacy and safety of intravenous versus subcutaneous immunoglobulin replacement therapy.J Clin Immunol. 2000; 20: 94-100Crossref PubMed Scopus (271) Google Scholar, 2Gardulf A. Nicolay U. Asensio O. Bernatowska E. Bock A. Carvalho B.C. et al.Rapid subcutaneous IgG replacement therapy is effective and safe in children and adults with primary immunodeficiencies–a prospective, multi-national study.J Clin Immunol. 2006; 26: 177-185Crossref PubMed Scopus (166) Google Scholar, 3Ochs H.D. Gupta S. Kiessling P. Nicolay U. Berger M. Safety and efficacy of self-administered subcutaneous immunoglobulin in patients with primary immunodeficiency diseases.J Clin Immunol. 2006; 26: 265-273Crossref PubMed Scopus (210) Google Scholar the question of the cost effect of this treatment remains an important economics question. Some pharmacoeconomic studies that compared SC-Ig with IV-Ig therapy have been performed in various countries,4Beaute J. Levy P. Millet V. Debre M. Dudoit Y. Le Mignot L. et al.Economic evaluation of immunoglobulin replacement in patients with primary antibody deficiencies.Clin Exp Immunol. 2010; 160: 240-245Crossref PubMed Scopus (58) Google Scholar, 5Gardulf A. Andersen V. Bjorkander J. Ericson D. Froland S.S. Gustafson R. et al.Subcutaneous immunoglobulin replacement in patients with primary antibody deficiencies: safety and costs.Lancet. 1995; 345: 365-369Abstract Full Text PDF PubMed Scopus (266) Google Scholar, 6Hogy B. Keinecke H.O. Borte M. Pharmacoeconomic evaluation of immunoglobulin treatment in patients with antibody deficiencies from the perspective of the German statutory health insurance.Eur J Health Econ. 2005; 6: 24-29Crossref PubMed Scopus (75) Google Scholar but their conclusions were not unequivocal, and, as reviewed by Membe et al,7Membe S.K. Ho C. Cimon K. Morrison A. Kanani A. Roifman C.M. Economic assessment of different modalities of immunoglobulin replacement therapy.Immunol Allergy Clin North Am. 2008; 28 (x): 861-874Abstract Full Text Full Text PDF PubMed Scopus (35) Google Scholar those studies could not be transposed to the Canadian or US health system. In 2007, when the Quebec government approved the use of SC-Ig, we offered our patients the choice between hospital-based IV-Ig and home-based SC-Ig, administered at equivalent doses. Most patients decided to switch to SC-Ig, allowing us to perform a retrospective pharmacoeconomic cohort study of 25 patients, in which we calculated expenditures for IV-Ig and then SC-Ig therapy over 2 consecutive years in the same cohort. Patients were eligible if they had been diagnosed with a primary immunodeficiency8Notarangelo L.D. Fischer A. Geha R.S. Casanova J.L. Chapel H. Conley M.E. et al.Primary immunodeficiencies: 2009 update.J Allergy Clin Immunol. 2009; 124: 1161-1178Abstract Full Text Full Text PDF PubMed Scopus (384) Google Scholar and received at least 1 year of uninterrupted IV-Ig before at least 1 year of uninterrupted SC-Ig. Because the literature clearly reported that both routes of administration were equivalent in terms of efficacy and safety,1Chapel H.M. Spickett G.P. Ericson D. Engl W. Eibl M.M. Bjorkander J. The comparison of the efficacy and safety of intravenous versus subcutaneous immunoglobulin replacement therapy.J Clin Immunol. 2000; 20: 94-100Crossref PubMed Scopus (271) Google Scholar, 2Gardulf A. Nicolay U. Asensio O. Bernatowska E. Bock A. Carvalho B.C. et al.Rapid subcutaneous IgG replacement therapy is effective and safe in children and adults with primary immunodeficiencies–a prospective, multi-national study.J Clin Immunol. 2006; 26: 177-185Crossref PubMed Scopus (166) Google Scholar, 3Ochs H.D. Gupta S. Kiessling P. Nicolay U. Berger M. Safety and efficacy of self-administered subcutaneous immunoglobulin in patients with primary immunodeficiency diseases.J Clin Immunol. 2006; 26: 265-273Crossref PubMed Scopus (210) Google Scholar a cost-minimization analysis was applied. Methods and allocation of unit costs for resource valuation from various sources are shown in Table E1 (see this article's Online Repository at www.jacionline.org) and patient characteristics in Table E2 (see this article's Online Repository at www.jacionline.org). As shown in Table I, the time spent by parents in taking care of their children's treatment was significantly greater for IV-Ig than for SC-Ig. In addition, estimated time spent by nurses, technicians, and administrative assistants was higher for patients treated with IV-Ig. We found that the cost of medical resources and the cost of nonmedical resources were both significantly lower when patients were treated with SC-Ig (P < .001 and P < .001, respectively; Table II). In addition, the total cost (medical plus nonmedical costs) associated with SC-Ig was significantly lower than that associated with IV-Ig ($6.488 ± $4.571 vs $10,761 ± $7,874 per patient per year; P < .001, respectively; Table II). In this calculation, the cost of immunoglobulins was not taken into consideration, although they were quite similar for the different groups. Indeed, in Quebec (and in the rest of Canada), there is parity in the price per gram of SC-Ig and IV-Ig. The cost of immunoglobulins by itself accounted for about 48% and 66% of the total cost of IV-Ig and SC-Ig therapy, respectively. Interestingly, the total expenditures, which include the cost of immunoglobulins, were still significantly higher for the IV-Ig than for the SC-Ig route ($23,845 ± $13,245 vs $19,044 ± $9,476 per patient per year; P < .001, respectively) despite this high proportion of cost for immunoglobulins. SJH, Ste-Justine Hospital. With respect to certain purchases such as pumps and infusion material that were covered by the hospital for IV-Ig and by the patients for SC-Ig, we adjusted our calculations for both a patient/parent perspective and a government/hospital one and found, as shown in Table II, that, all in all, the SC route remained less costly than the IV route from either the patient perspective (P < .001) or the government perspective (P < .001). We then performed a secondary analysis (sensitivity analysis) in which we considered only the loss of productivity for parents (ie, the number of hours parents declared to have spent away from their work to take care of their child), whereas for nurses we considered an estimated time that was based on an increased caseload of 5 patients per nurse instead of 2. On this basis, the total cost (medical plus nonmedical costs) was still significantly lower, as shown in Table E3 (see the Online Repository at www.jacionline.org), for SC-Ig compared with IV-Ig without or with including the cost of immunoglobulins (P < .001 and P = .03, respectively), thereby indicating that even considering this worst-case scenario (secondary analysis), the cost of SC-Ig therapy was significantly lower than that of IV-Ig therapy. From a patients perspective with the use of this secondary analysis as described, costs for patients were still less for SC-Ig than for IV-Ig, although statistical significance was not reached (P = .23), whereas from a government perspective, costs were still significantly less for SC-Ig than for IV-Ig (P < .001), even if the cost of immunoglobulins was taken into account (P = .03; see Table E3 in this article's Online Repository at www.jacionline.org). Interestingly, for the true cost of medications and medical consultations, no significant difference was observed between the 2 treatment groups (Table II). Expenditures related to the use of physicians were higher, although not statistically significant, for IV-Ig compared with SC-Ig, probably because patients treated with IV-Ig were charged for each monthly visit as opposed to every 4 to 6 months for those receiving SC-Ig. Costs for medications, which essentially comprised antibiotics, were similar for the 2 groups (Table II), suggesting that switching from IV-Ig to SC-Ig did not result in a higher number of infections. Moreover, the number of hospitalizations was similar for the 2 groups (data not shown). This retrospective study was performed within a single university-based hospital, which is less desirable than a prospective case–control study. However, by using each case as its own control provided considerable advantages, such as limiting selection bias, thereby making the 2 groups most comparable and also by eliminating inter-individual variability. Notwithstanding the small study sample size (n = 25), we found a statistically significant decrease, even in the secondary analysis, in both medical and nonmedical costs associated with switching from a hospital-based IV-Ig regime to that of a home-based SC-Ig regime. Furthermore, the results were consistent across the different payer perspectives whether it was the patient, the hospital, or the government. This is one of the first studies to address and encompass all of these various aspects. Another strong point is that most of our information was gathered from official, exhaustive, and computerized government sources, which minimized the need for cost estimates. Moreover, unlike other pharmacoeconomic studies,4Beaute J. Levy P. Millet V. Debre M. Dudoit Y. Le Mignot L. et al.Economic evaluation of immunoglobulin replacement in patients with primary antibody deficiencies.Clin Exp Immunol. 2010; 160: 240-245Crossref PubMed Scopus (58) Google Scholar, 5Gardulf A. Andersen V. Bjorkander J. Ericson D. Froland S.S. Gustafson R. et al.Subcutaneous immunoglobulin replacement in patients with primary antibody deficiencies: safety and costs.Lancet. 1995; 345: 365-369Abstract Full Text PDF PubMed Scopus (266) Google Scholar, 6Hogy B. Keinecke H.O. Borte M. Pharmacoeconomic evaluation of immunoglobulin treatment in patients with antibody deficiencies from the perspective of the German statutory health insurance.Eur J Health Econ. 2005; 6: 24-29Crossref PubMed Scopus (75) Google Scholar we observed that the cost differential was not related to any difference in the price of immunoglobulins, and, even when the price of immunoglobulins was not taken into account, the cost associated with SC-Ig treatment was significantly lower, suggesting that the observed differences were related to the other pharmacoeconomic factors. Importantly, none of our patients had any desire to switch back to hospital-based IV-Ig therapy (patients were questioned about this issue at every visit). Studies have found that treatment at home provides patients and their families with a better quality of life as related to several aspects, including treatment independence and convenience, mental health, school and social functioning, and family activities.9Gardulf A. Nicolay U. Math D. Asensio O. Bernatowska E. Bock A. et al.Children and adults with primary antibody deficiencies gain quality of life by subcutaneous IgG self-infusions at home.J Allergy Clin Immunol. 2004; 114: 936-942Abstract Full Text Full Text PDF PubMed Scopus (218) Google Scholar, 10Nicolay U. Kiessling P. Berger M. Gupta S. Yel L. Roifman C.M. et al.Health-related quality of life and treatment satisfaction in North American patients with primary immunedeficiency diseases receiving subcutaneous IgG self-infusions at home.J Clin Immunol. 2006; 26: 65-72Crossref PubMed Scopus (164) Google Scholar Thus, once patients switch from IV-Ig to SC-Ig, they are unlikely to switch back; hence, the pharmacoeconomic effect would be for the long term. Given that both treatment options are equally effective and safe,1Chapel H.M. Spickett G.P. Ericson D. Engl W. Eibl M.M. Bjorkander J. The comparison of the efficacy and safety of intravenous versus subcutaneous immunoglobulin replacement therapy.J Clin Immunol. 2000; 20: 94-100Crossref PubMed Scopus (271) Google Scholar, 2Gardulf A. Nicolay U. Asensio O. Bernatowska E. Bock A. Carvalho B.C. et al.Rapid subcutaneous IgG replacement therapy is effective and safe in children and adults with primary immunodeficiencies–a prospective, multi-national study.J Clin Immunol. 2006; 26: 177-185Crossref PubMed Scopus (166) Google Scholar, 3Ochs H.D. Gupta S. Kiessling P. Nicolay U. Berger M. Safety and efficacy of self-administered subcutaneous immunoglobulin in patients with primary immunodeficiency diseases.J Clin Immunol. 2006; 26: 265-273Crossref PubMed Scopus (210) Google Scholar the financial arguments for SC-Ig are appealing with greater expected benefits at less cost. This is particularly relevant in Quebec where the study was performed but could easily be applicable to most health care systems in the Western world. In several societies, most medical expenses are covered or reimbursed by the government, whereas in others the same expenses would be handled by private insurance or the individual directly. Our data show that, no matter what the circumstances, there are appreciable economic incentives in favor of home-based SC-Ig treatment. As stated in our study, the dose of SC-Ig was equivalent to the dose of IV-Ig, as is done in Europe,11Jolles S. Bernatowska E. de Gracia J. Borte M. Cristea V. Peter H.H. et al.Efficacy and safety of Hizentra((R)) in patients with primary immunodeficiency after a dose-equivalent switch from intravenous or subcutaneous replacement therapy.Clin Immunol. 2011; 141: 90-102Crossref PubMed Scopus (92) Google Scholar whereas US recommendations lean toward a 37% higher dose of SC-Ig.12Hagan J.B. Fasano M.B. Spector S. Wasserman R.L. Melamed I. Rojavin M.A. et al.Efficacy and safety of a new 20% immunoglobulin preparation for subcutaneous administration, IgPro20, in patients with primary immunodeficiency.J Clin Immunol. 2010; 30: 734-745Crossref PubMed Scopus (104) Google Scholar If the latter dosage had been used, it would have led to a 37% increase in the cost of immunoglobulins for the SC-Ig group, which in our model would have resulted in the matching of total expenditures for both treatments. The savings from other medical and nonmedical expenses, in turn, would still have offset this, as we have shown. This is especially relevant because the price of the product itself, which constitutes the bulk of the cost, is likely to change in the future. The benefits from the patient's perspective would also remain, facilitating their tolerability of the treatment and easing the burden for families, which in terms of macroeconomics and health care policies are still of the outmost importance. With the current efforts to improve efficiency in health care delivery and resource management, this type of pharmacoeconomic study could become an example of how to realistically transform a costly therapy for a chronic illness into a more economical and patient-oriented alternative, especially considering the lasting monetary effect on the health care system, which should be substantial. Mark Abramovitz, a medical writer, was supported by funding from La Fondation Charles-Bruneau for editorial assistance to the authors during the preparation of this manuscript. AppendixTable E1Allocation of unit costs for resource valuationType of utilizationMode of evaluationUnit cost ($CAD)Sources for unit costMedical resources Nurse, technicianEstimated time per patient28.75 per hour∗Source: registered nurse (RN), Fédération interprofessionnelle du Québec (FIQ).CHU Ste-Justine Administrative assistantEstimated time per patient19.20 per hourCHU Ste-Justine Immunoglobulin productReal cost, calculated for each patient by reviewing chart57 per gram of immunoglobulinHéma-Québec Dispensing by blood bankEstimated time28.75 per hour∗Source: registered nurse (RN), Fédération interprofessionnelle du Québec (FIQ).CHU Ste-Justine PumpReal cost, 1 per patient136CHU Ste-Justine Infusion materialsEstimated cost3.94 (Burethrol), 3.49 (infusion tubing), 3.50 (Jelco per unit)CHU Ste-Justine Preparation of infusion materialsEstimated time per patient28.75 per hour∗Source: registered nurse (RN), Fédération interprofessionnelle du Québec (FIQ).CHU Ste-Justine PharmaceuticalsReal cost, obtained for each patientGovernment (RAMQ) Pediatric consultationsReal cost, obtained for each patientGovernment (RAMQ) Other medical servicesReal cost, obtained for each patientGovernment (RAMQ)Nonmedical resources Travel by private carQuestionnaire for each patient0.47 per km†Flat rate of $0.47 per km (http://www.caa.ca/documents/CAA_Driving_Costs_Brochure_2010.pdf as of July 21, 2010).CAA Travel by public transportQuestionnaire for each patient3.00 per tripSTM Travel by taxisQuestionnaire for each patient3.30 + 1.70 per km, per tripMontreal, City Hall ParkingQuestionnaire for each patient12.00 per dayCHU Ste-Justine HotelQuestionnaire for each patient120.00 per nightCHU Ste-Justine Loss of productivity‡The costs of lost productivity were estimated by multiplying the amount of lost time reported by the average daily wage for Canadian employees in 2010. The expenditures of assistance from relatives and paid assistance were estimated with the average hourly wage for employees in Canada.Questionnaire for each patient23.10 per hourStatistics Canada§Average wages (men and women) from Statistics Canada as of July 2010.Demographics and clinical data were acquired by a retrospective chart review. Medical direct treatment costs and economic data were captured from a number of sources and through questionnaires specifically developed for the study. The study was approved by the Ethics Committee of Ste-Justine Hospital and the "Commission d'Accès à l'Information du Québec" to obtain authorization for database access and linkage to patient information. All patients signed informed consents before study entry. Information on resource utilization and costs was retrieved from 2 provincial government health care databases: RAMQ (Regime de l'Assurance Maladie du Québec) and Med-Echo. The RAMQ database collects data on outpatient prescription drugs dispensed by community pharmacies (drug identification number, dispensing date, dose, treatment duration, and quantity of drug dispensed), in-patient and out-patient physician visits (date of visit, specialty of the physician, and ICD9 diagnostic code). The Med-Echo database maintained by the Ministry of Health and Social Services of Quebec (MSSS) provides information on all hospital admissions in Quebec (date of admission, length of stay, primary discharge diagnosis).CAA, Canadian Automobile Association; RAMQ, Régie de l'Assurance Maladie du Québec; STM, Société de Transport de Montréal.∗ Source: registered nurse (RN), Fédération interprofessionnelle du Québec (FIQ).† Flat rate of $0.47 per km (http://www.caa.ca/documents/CAA_Driving_Costs_Brochure_2010.pdf as of July 21, 2010).‡ The costs of lost productivity were estimated by multiplying the amount of lost time reported by the average daily wage for Canadian employees in 2010. The expenditures of assistance from relatives and paid assistance were estimated with the average hourly wage for employees in Canada.§ Average wages (men and women) from Statistics Canada as of July 2010. Open table in a new tab Table E2Patient characteristics (n = 25)ValueAge at initial diagnosis (y), mean ± SD [median]6.5 ± 4.0 [5]Age at index date∗Defined as date of switch to SC-Ig therapy. (y), mean ± SD [median]11.7 ± 4.4 [13]Sex (male), no. (%)10 (40)Weight∗Defined as date of switch to SC-Ig therapy. (kg), mean ± SD [median]35.7 ± 16.6 [36]No. of months since start of immunoglobulin therapy, mean ± SD [median]42.9 ± 41.8 [24]Patients had the following diagnoses: 18, common variable immunodeficiency (CVID); 4, combined immunodeficiency (CID); 1, Di George syndrome; 2, X-linked lymphoproliferative syndrome (XLP) with a CVID-like phenotype.∗ Defined as date of switch to SC-Ig therapy. Open table in a new tab Table E3Secondary analysis of medical and nonmedical resource costs over the first year, $CAD per patientIV, mean ± SDSC, mean ± SDSC-Ig minus IV-Ig, mean (95% CI)P value (signed rank test)Nonmedical resources (1) Travel expensesTransports (taxi, bus, metro, own car)773 ± 921193 ± 230−580 (−865 to −295)Hotel182 ± 47646 ± 119−137 (−284 to 11)Parking63 ± 7316 ± 18−48 (−70 to −25)Totals1,019 ± 1,222255 ± 305−764 (−1142 to −386)<.001 (2) Loss of productivity∗Loss of productivity per year for parents was evaluated as 52 ± 135 hours versus 1 ± 3 hours for IV-Ig and SC-Ig, respectively.1,120 ± 3,119†Numerical differences between this table and Table II.16 ± 80†Numerical differences between this table and Table II.−1204 (−2494 to 87).06†Numerical differences between this table and Table II. (3) Other resources (Emla cream)<169 ± 12669 (17 to 121).03 Total nonmedical resources (1) + (2) + (3)2,239 ± 3,767†Numerical differences between this table and Table II.340 ± 341†Numerical differences between this table and Table II.−1899 (−3388 to −409)†Numerical differences between this table and Table II.<.001†Numerical differences between this table and Table II.Medical resources (4) Nurse, technician, administration‡The estimated time spent by nurses per patient per year was 24 hours for IV-Ig (mainly watching over patients) versus 1.5 hours for SC-Ig (mainly in teaching patients how to administer their treatment). (SJH)832†Numerical differences between this table and Table II.95†Numerical differences between this table and Table II.−737†Numerical differences between this table and Table II. (5) Pump, infusion materials136780+644 (6) Medical services (consultations)2,685 ± 5,5081,918 ± 2,882−767 (−2853 to 1318).14 (7) Pharmaceuticals1,367 ± 3,6301,387 ± 3,16420 (−1024 to 1063).81 Total medical resources (4) + (5) + (6) + (7)5,020 ± 6,197†Numerical differences between this table and Table II.4,180 ± 4,495†Numerical differences between this table and Table II.−841 (−2385 to 704)†Numerical differences between this table and Table II..021†Numerical differences between this table and Table II. Total medical and nonmedical resources7,259 ± 8,242†Numerical differences between this table and Table II.4,520 ± 4,644†Numerical differences between this table and Table II.−2739 (−5021 to −458)†Numerical differences between this table and Table II.<.001†Numerical differences between this table and Table II.Immunoglobulins13,084 ± 9,22512,556 ± 8,046−528 (−1716 to 660).36Total medical and nonmedical resources + immunoglobulins20,343 ± 13,351†Numerical differences between this table and Table II.17,075 ± 9,164†Numerical differences between this table and Table II.−3267 (−6055 to −480)†Numerical differences between this table and Table II..03†Numerical differences between this table and Table II.Cost according to perspective Patient perspective (1) + (2) + (3) + (5) (only for SC)2,239 ± 3,767†Numerical differences between this table and Table II.1,120 ± 341†Numerical differences between this table and Table II.−1119 (−2608 to 371)†Numerical differences between this table and Table II..23†Numerical differences between this table and Table II. Government perspective (4) + (5) (only for IV) + (6) + (7)5,020 ± 6,197†Numerical differences between this table and Table II.3,400 ± 4,495†Numerical differences between this table and Table II.−1621 (−3165 to −76)†Numerical differences between this table and Table II.<.001†Numerical differences between this table and Table II.In this secondary analysis we based the loss of productivity for parents on the number of hours parents declared to have spent away from their work to take care of their child, whereas for nurses we considered an estimated time that was based on an increased caseload of 5 patients per nurse instead of 2, which both decreased the monetary difference between hospital and home-based care.SJH, Ste-Justine Hospital.∗ Loss of productivity per year for parents was evaluated as 52 ± 135 hours versus 1 ± 3 hours for IV-Ig and SC-Ig, respectively.† Numerical differences between this table and Table II.‡ The estimated time spent by nurses per patient per year was 24 hours for IV-Ig (mainly watching over patients) versus 1.5 hours for SC-Ig (mainly in teaching patients how to administer their treatment). Open table in a new tab Demographics and clinical data were acquired by a retrospective chart review. Medical direct treatment costs and economic data were captured from a number of sources and through questionnaires specifically developed for the study. The study was approved by the Ethics Committee of Ste-Justine Hospital and the "Commission d'Accès à l'Information du Québec" to obtain authorization for database access and linkage to patient information. All patients signed informed consents before study entry. Information on resource utilization and costs was retrieved from 2 provincial government health care databases: RAMQ (Regime de l'Assurance Maladie du Québec) and Med-Echo. The RAMQ database collects data on outpatient prescription drugs dispensed by community pharmacies (drug identification number, dispensing date, dose, treatment duration, and quantity of drug dispensed), in-patient and out-patient physician visits (date of visit, specialty of the physician, and ICD9 diagnostic code). The Med-Echo database maintained by the Ministry of Health and Social Services of Quebec (MSSS) provides information on all hospital admissions in Quebec (date of admission, length of stay, primary discharge diagnosis). CAA, Canadian Automobile Association; RAMQ, Régie de l'Assurance Maladie du Québec; STM, Société de Transport de Montréal. Patients had the following diagnoses: 18, common variable immunodeficiency (CVID); 4, combined immunodeficiency (CID); 1, Di George syndrome; 2, X-linked lymphoproliferative syndrome (XLP) with a CVID-like phenotype. In this secondary analysis we based the loss of productivity for parents on the number of hours parents declared to have spent away from their work to take care of their child, whereas for nurses we considered an estimated time that was based on an increased caseload of 5 patients per nurse instead of 2, which both decreased the monetary difference between hospital and home-based care. SJH, Ste-Justine Hospital.
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