Latent therapeutic demand model for the immunoglobulin replacement therapy of primary immune deficiency disorders in the USA.

BACKGROUND AND OBJECTIVES: Our research aim is to model latent therapeutic demand (LTD) for the immunoglobulin replacement therapy (IgGRT) of primary immune deficiency disorders (PIDDs) in the USA. Given the high level of variability of IgGRT use and major differences among American and European practices in the management of patients with PIDDs, we develop a USA-specific LTD model for common variable immune deficiency (CVID), hyper IGM syndrome, severe combined immune deficiency, Wiskott-Aldrich syndrome and X-linked agammaglobulinemia (XLA). METHODS AND MATERIALS: We use decision analysis methods to model the underlying IgGRT demand for PIDDs by assessing USA-specific epidemiology and treatment. Data for the epidemiology and treatment variables were obtained from the medical literature, USIDNET and Immune Deficiency Foundation. The uncertainty surrounding the variables was modelled using probability distributions and evaluated using Monte Carlo simulation. RESULTS: The mean treatment dose from USIDNET and European Society for Immunodeficiencies (ESID) was significantly different for treating CVID, and the number of annual infusions from USIDNET and ESID was significantly different for treating CVID and XLA. The mean and standard deviation of LTD for all PIDDs is 105·1 ± 88·5 g per 1000 population, with CVID contributing the most to LTD. CONCLUSION: Estimating country-specific LTD is important to ensure an adequate supply of IgGRT and an optimal treatment for patients with PIDDs and for improving national healthcare policymaking and production planning.

The Patient Reported Outcomes, Burdens and Experiences (PROBE) Project: development and evaluation of a questionnaire assessing patient reported outcomes in people with haemophilia.

BACKGROUND: The interest of health care agencies, private payers and policy makers for patient-reported outcomes (PRO) is continuously increasing. There is a substantial need to improve capacity to collect and interpret relevant PRO data to support implementation of patient-centered research and optimal care in haemophilia. The Patient Reported Outcomes, Burdens and Experiences (PROBE) Project aims to develop a patient-led research network, to develop a standardized questionnaire to gather patient-reported outcomes and to perform a feasibility study of implementing the PROBE questionnaire. METHODS: A pilot questionnaire was developed using focus group methodology. Content and face validity were assessed by a pool of persons living with haemophilia (PWH) and content experts through interactive workshops. The PROBE questionnaire was translated with the forward-backward approach. PROBE recruited national haemophilia patient non-governmental organizations (NGOs) to administer the questionnaire to people with and without haemophilia. PROBE measured the time to complete the questionnaire and gathered feedback on its content and clarity; staff time and cost required to implement the questionnaire were also collected. RESULTS: The PROBE questionnaire is comprised of four major sections (demographic data, general health problems, haemophilia-related health problems and health-related quality of life using EQ-5D-5L and EQ-VAS). Seventeen NGOs participated in the pilot study of the PROBE Project, recruiting 656 participants. Of these, 71% completed the questionnaire within 15 min, and all participants completed within 30 min. The median total staff and volunteer time required for the NGOs to carry out the study within their country was 9 h (range 2 to 40 h). NGO costs ranged from $22.00 to $543.00 USD per country, with printing and postage being the most commonly reported expenditures. CONCLUSIONS: The PROBE questionnaire assesses patient-important reported outcomes in PWH and control participants, with a demonstrated short completion time. PROBE proved the feasibility to engage diverse patient communities in the structured generation of real-world outcome research at all stages. TRIAL REGISTRATION: Trial registration: NCT02439710.

Measuring the quality of haemophilia care across different settings: a set of performance indicators derived from demographics data.

BACKGROUND: Haemophilia is a rare disease for which quality of care varies around the world. We propose data-driven indicators as surrogate measures for the provision of haemophilia care across countries and over time. MATERIALS AND METHODS: The guiding criteria for selection of possible indicators were ease of calculation and direct applicability to a wide range of countries with basic data collection capacities. General population epidemiological data and haemophilia A population data from the World Federation of Hemophilia (WFH) Annual Global Survey (AGS) for the years 2013 and 2010 in a sample of 10 countries were used for this pilot exercise. RESULTS: Three indicators were identified: (i) the percentage difference between the observed and the expected haemophilia A incidence, which would be close to null when all of the people with haemophilia A (PWHA) theoretically expected in a country would be known and reported to the AGS; (ii) the percentage of the total number of PWHA with severe disease; and (iii) the ratio of adults to children among PWHA standardized to the ratio of adults to children for males in the general population, which would be close to one if the survival of PWHA is equal to that of the general population. Country-specific values have been calculated for the 10 countries. CONCLUSIONS: We have identified and evaluated three promising indicators of quality of care in haemophilia. Further evaluation on a wider set of data from the AGS will be needed to confirm their value and further explore their measurement properties.

A study of variations in the reported haemophilia B prevalence around the world.

The objectives of this article were to study the reported prevalence of haemophilia B (HB) on a country-by-country basis and to analyse whether the prevalence of HB varied by national economy. The prevalence of HB is the proportion of diagnosed, reported cases of HB in a population at a specific point of time. We collected data on the HB prevalence for 105 countries from the World Federation of Hemophilia annual global surveys. Our results showed that the HB prevalence varied considerably among countries, even among the wealthiest of countries. The HB prevalence (per 100 000 males) for the highest income countries was 2.69 ± 1.61 (mean ± SD), whereas the prevalence for the rest of the world was 1.20 ± 1.33 (mean ± SD). Ireland had the highest reported HB prevalence of 8.07 per 100 000 males. There was a strong trend of increasing HB prevalence (per 100 000 males) over time. Prevalence data reported from the WFH compared well with prevalence data from the literature. The WFH annual global surveys have some limitations, but they are the best available source of worldwide haemophilia data. Prevalence data are extremely valuable information for the planning efforts of national healthcare agencies in setting priorities and allocating resources for the treatment of HB.

A study of reported factor IX use around the world.

Replacement therapy has significantly improved the life expectancy and lifestyle of people with haemophilia. The objectives of this article were to study the reported factor IX (FIX) use on a country-by-country basis and address the following question: Does the reported FIX use vary by national economies? We obtained data on the reported number of international units (IUs) of FIX used for 90 countries from the Marketing Research Bureau and the World Federation of Hemophilia. Results show that the reported FIX use varies considerably across national economies, even among the wealthiest of countries.Trends suggest that the reported FIX usage increases with increasing economic capacity and has been increasing over time. Trends also suggest that consumption of FIX has been increasing at a greater rate in high income countries. Given these trends, there will likely be an overall increase in the amount of FIX concentrates used in the treatment of haemophilia B. We also found that FIX use both in terms of IUs per capita and IUs per person provide a complete picture of the level of haemophilia care within a country. Such information is critical for planning efforts of national healthcare agencies to determine realistic budget priorities and pharmaceutical manufacturers to determine adequate production levels of FIX concentrates. By improving the data collection and surveillance of FIX use for the treatment of people with haemophilia B, we can identify trends and needs of patients and highlight best treatment practices among countries.

A study of reported factor VIII use around the world.

The effect of replacement therapy has significantly improved the morbidity and mortality of people with haemophilia A in high income countries, a recent socio-economic development as the availability of safe concentrates has been matched by a willingness for their provision through reimbursement. In the developing world, however, this state has not been achieved, primarily because of the low visibility of haemophilia coupled with its expense, leading to inadequate treatment with its sequelae of severe pain, joint deformities, arthropathy, disabilities, and even death in childhood or early adult life. The objective of this paper was to study the reported factor VIII (FVIII) use on a country-by-country basis. Data on the reported FVIII use for 104 countries were obtained from the Marketing Research Bureau, Inc. and the World Federation of Hemophilia. The results show that FVIII use varies considerably among countries, even among the wealthiest of countries. The use of FVIII concentrate increases as economic capacity increases; in addition, consumption of FVIII has been increasing at a greater rate in high income countries. Given these trends, there probably will be a global increase in FVIII concentrates usage. Such information is critical for national healthcare agencies to determine realistic budget priorities in planning for an increased allocation of resources required to improve the treatment of patients with haemophilia A. This information is also important for pharmaceutical manufacturers to adequately plan for increased production of FVIII concentrates.

A study of variations in the reported haemophilia A prevalence around the world.

The objectives of this paper were to study the reported haemophilia A prevalence (per 100 000 males) on a country-by-country basis and address the following: Does the reported prevalence of haemophilia A vary by national economies? We collected prevalence data for 106 countries from the World Federation of Hemophilia (WFH) annual global surveys and the literature. We found that the reported haemophilia A prevalence varied considerably among countries, even among the wealthiest of countries. The prevalence (per 100 000 males) for high income countries was 12.8 +/- 6.0 (mean +/- SD) whereas it was 6.6 +/- 4.8 for the rest of the world. Within a country, there was a strong trend of increasing prevalence over time--the prevalence for Canada ranged from 10.2 in 1989 to 14.2 in 2008 (R = 0.94 and P < 0.001) and for the United Kingdom it ranged from 9.3 in 1974 to 21.6 in 2006 (R = 0.94 and P < 0.001). Prevalence data reported from the WFH compared well with prevalence data from the literature. Patient registries generally provided the highest quality of prevalence data. The lack of accurate country-specific prevalence data has constrained planning efforts for the treatment and care of people with haemophilia A. With improved information, healthcare agencies can assess budgetary needs to develop better diagnostic and treatment facilities for affected patients and families and work to ensure adequate supplies of factor VIII concentrates for treatment. In addition, this information can help manufacturers plan the production of concentrates and prevent future shortages.

Modelling haemophilia epidemiology and treatment modalities to estimate the unconstrained factor VIII demand.

The article presents a new method for estimating the unconstrained factor VIII (FVIII) demand based on the principles of decision analysis. Epidemiology and treatment modalities were integrated into a model for unconstrained FVIII demand. Assumptions for each variable with impact on the unconstrained FVIII demand were defined and probability estimates for these variables were obtained from the literature and medical experts. The sensitivity of the unconstrained FVIII demand to each of the variables was determined, and the variables with the greatest impact were modelled probabilistically. The probability-weighted average for the unconstrained FVIII demand model was 6.9 units per capita with a 90% uncertainty interval of 2.7-13.6 units per capita. When compared with FVIII usage in countries, only Luxembourg's use of FVIII (7.7 units per capita) exceeded the probability-weighted average for the modelled unconstrained FVIII demand. As better information becomes available, revision of model variables is easily accomplished allowing for a more accurate and dynamic forecast of demand over time. More accurate modelling of the 'true' demand longitudinally should help prevent shortages of FVIII concentrates such as those that have occurred in the past. In addition, a more accurate forecast of FVIII demand will allow national health care policy makers to better allocate financial and other resources. Sufficient and consistent supply of FVIII concentrates and appropriate financing of haemophilia care will allow the clinical benefits of more aggressive treatment regimens such as prophylaxis to be realized.

A country-by-country comparison of FVIII concentrate consumption and economic capacity for the global haemophilia community.

The article presents a method to estimate the level of factor VIII (FVIII) concentrate consumption and economic capacity for each of the 110 countries considered in the study. A number of health-economic indicators were examined and purchasing power parity (PPP) gross national income (GNI) per capita had the strongest correlation with amount of FVIII concentrates sold in a country. Available data on FVIII concentrate consumption and health-economic indicators were used to calculate index values for FVIII use and economic capacity so each country can assess and compare its level of FVIII concentrate consumption with the economic resources of other countries in the global haemophilia A community. This article is of importance to policy makers, care givers and patient organizations in planning health-care resources for the treatment of haemophilia.