Research Studies

Objective:

To evaluate changes in healthcare resource utilization and haemophilia related events among patients diagnosed with haemophilia A between 2008 and 2012.

Methods:

This retrospective study analyzed data from the Humedica de-identified electronic medical record database between January 2008 and December 2012. Male patients diagnosed with hemophilia A (ICD-9-CM 286.0) receiving treatment with a clotting factor were eligible if they 1) were ≥18 years of age 2) did not receive Factor IX therapy and 3) did not have a diagnosis of Von Willebrand while receiving factor VIII therapy containing von Willebrand factor. All patient level resource utilization was converted to utilization per patient year. Resource utilization was then compared across time periods using repeated measures analysis of variance (ANOVA). The annualized number of haemophilia related events (haemophilic arthropathy or other joint related events) was calculated for each year. McNemar’s chi-square test was used to compare the frequencies across years.

Summary:

136 patients contributing 375 patient-years were included in this study. Office/clinic visits accounted for the majority of healthcare encounters annually; 7.5 all-cause visits per year and 2.2 haemophilia related visits per year. The number of annual all-cause office/clinic visits for Haemophilia A patients decreased significantly over time from 12.5 visits in 2008 to 5.9 visits in 2012 (p=0.0404), while haemophilia A-specific annual visits decreased from 4.0 to 1.5 (p=0.1991) during the same period. On average haemophilia A patients had less than 1 inpatient and emergency room visits per year, which did not change significantly over time (p=0.6371 and p=0.4845, respectively). Over the 5-year period, haemophilic events occurred in 30.93% of patient years, changed from 23.81% in 2009 to 34.09% in 2011 (p=0.6658).

Conclusions:

Office/clinic outpatient visits among patients diagnosed with haemophilia A has decreased overtime. However, the rate of haemophilia related arthropathies and other associated events have remained high. Further analysis is needed to understand how to best manage patients diagnosed with haemophilia A and reduce the proportion of patients who develop reduced joint mobility due to bleeding into joints.

Objective:

To analyse real-world FIX dosing and treatment interval patterns. A secondary objective was to compare the observed dosing patterns with the dosing regimens for FIX products evaluated in clinical studies.

Methods:

A retrospective analysis was conducted using aggregate Specialty Pharmacy Provider (SPP) records from 2012 through Q12014. SPP data included 63 different attributes for each prescription, including trade name, NDC, quantity shipped, prescribed infusion dose, days supplied, and dose frequency. Patients were considered eligible for the analysis if they received a shipment of any FIX product. Patients were excluded from the analysis if they were being treated episodically, for immune tolerance induction, or their pharmacy records did not specify a prescribed infusion dose. Patients with missing or extremely abnormal weights were also excluded. The patient’s weekly consumption was calculated for each shipment record by multiplying the prescribed infusion dose by the dose frequency and dividing the product by the patient’s weight, resulting in the patient’s average weekly prescribed dose (IU/kg/week). Patients were also categorized according to dosing interval.

Summary:

The analysis included 118 hemophilia B patients with a median age of 20 (range: 2-63) and median weight of 55.4 kg (range: 9.5-129 kg). Pharmacy dispensing records represented 78 distinct prescribers across 29 states. FIX therapies evaluated included Benefix®, Alphanine®, Mononine®, and Rixubis®. The average weekly consumption across all therapies was 139.0 IU/kg/week (95% CI, 128.7-150.3). Dosing frequency ranged from every other day to once weekly. Twice weekly was the most common dosing interval, representing 56.8% of patient records. According to clinical trial data and FDA labelled dosing for FIX therapies, lower weekly consumption may be expected. For BeneFIX the mean weekly consumption was 80.6 IU/kg, 40.3 IU/kg administered twice-weekly. For Rixubis the mean weekly consumption was 88.9 IU/kg, 49.4 IU/kg administered 1.8 times/week and a US dosing recommendation of 40-60 IU/kg dosed twice-weekly. Two prophylactic regimens have been evaluated for AlprolixTM. In the last 3 months of B-LONG, in the weekly prophylaxis arm, the overall median dose on study was 40.5 IU/kg. The individualized interval prophylaxis arm had a median weekly dose of 50.0 IU/kg, 100 IU/kg administered every 14 days. No real world dosing is available for Alprolix due to its recent approval.

Conclusions:

Dosing regimens evaluated in the real world for conventional FIX products indicate greater consumption than reported in clinical trials. This may result in unpredictability for payers who are responsible for healthcare budgets.

Objective:

To investigate the prevalence of comorbidities among adults with hemophilia in the Hemophilia Utilization Group Studies (HUGS)

Methods:

Standardized interviews were conducted for two prospective cohort studies HUGS- Va (hemophilia A) and HUGS-Vb (hemophilia B) at six and ten US Hemophilia Treatment Centers, respectively, between 2005 and 2011. Clinical records were reviewed. Information captured included self-reported comorbidities, sociodemographics, treatment patterns and other clinical characteristics. Overweight and obesity were defined as body mass index (BMI) 25-29 kg/m2 and BMI ≥30 kg/m2, respectively. The prevalence of comorbidities was calculated. The association of comorbidities with hemophilic severity, age and type of hemophilia were assessed using appropriate statistical methods for categorical or continuous variables.

Summary:

The analyses included a total of 213 adults (HUGS-Va: n=147, HUGS-Vb: n=66) aged 20 to 65 years (mean±standard deviation: 36.6±12.9). Approximately, 64% of hemophilia A and 44% of hemophilia B individuals had severe hemophilia. The five most prevalent self-reported comorbidities were liver disease/hepatitis (66%), overweight/obesity (60%), arthritis (51%), human immunodeficiency virus infection/acquired immunodeficiency syndrome (HIV/AIDS) (24%), and hypertension (23%). The individuals in the hemophilia A sample were more likely to report liver disease/hepatitis (71% vs. 53%) and HIV/AIDS (30% vs. 9%) than those in the hemophilia B sample (all p<0.009). The prevalence of overweight/obesity (59% vs. 60%), arthritis (55% vs. 42%), and hypertension (22% vs. 24%) were not significantly different between hemophilia A and hemophilia B samples (all p>0.05). Prevalence of comorbidities was greater among individuals with severe than mild/moderate hemophilia for most conditions: liver disease/hepatitis (79% vs. 48%), arthritis (61% vs. 38%), HIV/AIDS (37% vs. 6%), and stroke/brain haemorrhage (11% vs. 2%) (all p<0.02), the exception being overweight/obesity (52% vs. 70%, p=0.007). The individuals with hemophilia A had a significantly greater number of comorbidities than those with hemophilia B (mean±standard deviation: 2.5±1.9 vs. 1.0±1.1; p<0.0001); 85% of the hemophilia A sample reported having more than one comorbidity compared to 61% of those with hemophilia B (p<0.0001). The number of comorbidities increased significantly with advancing age (p<0.0001).

Conclusions:

As one of the largest prospective studies of persons with hemophilia, the HUGS sample is representative of the US hemophilia A and B populations. Except for overweight/obesity, the most prevalent comorbidities reported in HUGS related to their hemophilia complications, and were significantly associated with hemophilic severity. As the life expectancy of persons with hemophilia increases, the need for studies focusing on the health care needs of individuals with hemophilia and comorbid conditions will increase.

Objectives:

Factor VIII (FVIII) prophylaxis regimens for severe hemophilia A that allow more flexible dosing than the standard 3-times-weekly regimen while maintaining efficacy may improve adherence. This analysis compared the clinical efficacy of once- or twice-weekly versus ≥3-times-weekly prophylaxis dosing of Bayer’s sucrose-formulated recombinant FVIII (rFVIII-FS) in patients with severe hemophilia A.

Methods:

Data from 3 postmarketing studies were pooled. Patients with severe hemophilia A and no history of inhibitors who were receiving ≥1 prophylaxis infusion/wk of rFVIII-FS for ≥80% of a prophylaxis observation period (≥5 months) were included. Patients were categorized based on age (<18 and ≥18 years) and physician-assigned treatment regimens of 1–2 prophylaxis injections/wk (n=63) or ≥3 prophylaxis injections/wk (n=76). Descriptive statistics were determined for annualized bleeding rates (ABRs) by dosing group and age subgroups.

Summary:

Median (quartile 1; quartile 3) ABR for all bleeds was 2.0 (0; 4.0) in the group receiving 1–2 prophylaxis injections/wk and 3.9 (1.5; 9.3) in the group with ≥3 prophylaxis injections/wk. Similarly, median ABRs for joint, spontaneous, and trauma-related bleeds were numerically lower in the group receiving 1–2 prophylaxis injections/wk. The trend toward lower ABRs in the group with 1–2 prophylaxis injections/wk was observed in both age subgroups, although ABRs were somewhat higher in patients ≥18 vs <18 years. Zero annualized bleeds were reported by 30% and 7% of patients in the groups with 1–2 prophylaxis injections/wk and ≥3 prophylaxis injections/wk, respectively.

Conclusions:

These data demonstrate that bleeding control can be achieved in some patients with severe hemophilia A using a <3-times-weekly prophylaxis dosing regimen and that physicians’ judgment based on bleeding phenotype can successfully direct the frequency of prophylactic dosing.

Objective:

Baxter has developed BAX 855, a PEGylated form of Baxter’s recombinant full length FVIII (rFVIII) product based on the ADVATETM manufacturing process. Here we describe it ́s manufacturing and structural and functional characterization.

Methods:

A rFVIII intermediate of the ADVATETM manufacturing process is the starting material for the conjugation process for preparing BAX 855 by proprietary PEGylation technology from Nektar Therapeutics. Similar technology has been successfully employed for marketed and licensed PEGylated drug products and drugs in clinical use. The manufacturing process for BAX 855 comprises several steps, including controlled PEGylation followed by cation exchange chromatography. Final formulation uses the same excipients as ADVATETM. BAX 855 was characterized by a number of analytical methods, focusing on the elucidation of the primary structure, posttranslational modifications, PEGylation site distribution and three- dimensional structure. The overall hemostatic potency of BAX 855 in FVIII-deficient plasma was assessed by conventional FVIII 1-stage clotting and chromogenic assays and with a thrombin generation assay. The tenase cofactor activity of FVIII was determined by measuring the kinetics of FXa generation. Binding of BAX 855 in comparison to ADVATETM was determined to its ligands VWF and low-density lipoprotein-receptor-related protein (LRP).

Summary and Conclusions:

BAX 855 is a full-length rFVIII with extended half-life. PK studies in different animal species and humans with hemophilia A display longer survival of BAX 855 compared to ADVATETM. The product is based on the original, native FVIII protein utilized in the production of ADVATETM. Our analyses show that BAX 855 can be manufactured reproducibly without changes to the protein structure characteristic for a fully functional full-length rFVIII molecule. The process is suited to manufacture BAX 855 in large scale and showed a good batch to batch consistency, ensuring an equivalent product quality for each batch. BAX 855 has a specific activity similar to that of rFVIII in ADVATETM and PEGylation degrees in the range of 2 to 3 mol PEG / mol rFVIII. SDS-PAGE and Western blot analysis of BAX 855 confirm PEGylation and demonstrate an increase in the molecular weight of the various FVIII domains.

In comparison to ADVATETM the functional properties of BAX 855 were fully retained except for binding to LRP, indicating that PEGylation did not have an impact on the functional properties of rFVIII. The latter might explain why BAX 855 shows prolonged survival in the circulation of hemophilic species and patients with hemophilia A than ADVATETM.

Objective:

This poster outlines evaluation of an educational family board game, “Don’t Push Your Luck!” designed to inspire discussion about hemophilia, and help school-age children learn about decision-making. Since children with hemophilia have a life-long disorder, this game provides a resource to help them learn how to make decisions for transitions to self- care.

Methods:

This game was developed based on recommendations by school-age children from previous research on partnership roles in hemophilia care. In the game, each player takes on the role of a child with hemophilia, exploring choices and consequences in everyday experiences. A multi-site, mixed method research project was coordinated by Mount Royal University, with sub-sites in Canada and United States. In phase I, the board game prototype and questionnaires from boys (n=3) and parents (n=5) living with hemophilia and boys (n=3) and parents (n=5) living with cystic fibrosis was refined. In phase II, we evaluated the revised version of the board game with children who were living with hemophilia and their household family members over age 8 years. The primary objective was to explore how playing an educational board game affected school age children’s engagement in decision-making for self-care. Children and parent perspectives were compared in the way the board game affects engagement in decision-making for children’s hemophilia self-care. Recommendations for future board game development were solicited. Purposive sampling was used to recruit household family members (n=50), including at least one parent/guardian (n= 22) and children aged 8-12 years living with hemophilia (n= 16). Two researchers visited homes to play the game, interview families, observe their responses to the game, and provide pre and post-game questionnaires on decision-making and Haemo-Quol Index© quality of life, and post-game enjoyment. Audio recordings and field notes were documented to record participant observation. Questionnaire items on decision making, quality of life observations, and game enjoyment were analyzed using descriptive statistics. Qualitative analysis of written, verbal and observed behaviours was summarized in thematic categories provided further evaluation of the board game intervention.

Summary:

Comparisons between children and adults were analyzed. Findings indicate that this game is an enjoyable and effective resource for school-age families to engage in discussions relevant to hemophilia self-care skills and decision-making.

Conclusion:

This board game is an interactive, developmentally appropriate resource for families with school-age children who are living with hemophilia to facilitate engagement and conversation about everyday life experiences in preparation for their transition to adult self- care.

This project was generously funded by an unrestricted grant from Bayer Healthcare.

Objectives:

To determine the relationship between von Willebrand disease (vWD), dental plaque, and gingival bleeding in women with vWD and to determine the oral hygiene habits and dental care utilization in women with vWD.

Methods:

Consenting adult women with vWD (n=40) will have been recruited for this study. A questionnaire was given with 34 items covering topics such as dental care utilization, oral health quality of life, and oral hygiene habits. A brief oral examination was performed on each subject to assess which surfaces of the six Ramfjord teeth presented with dental plaque, and which surfaces bled upon flossing. Information was also gathered about each subject’s medical history, including the type of vWD, severity, and last von Willebrand factor levels.

Summary:

Data is still being collected for this study. Data collection will be completed on June 30. The data gathered so far shows that the majority of women who participated in this study have a high plaque score, yet minimal bleeding with flossing, when a gentle c-wrap flossing technique was performed.

Conclusions:

Results of this study are expected to show that the bleeding disorder has minimal effect on the amount of gingival bleeding that occurs with a c-wrap flossing technique. It’s possible that conclusions may be made that correct flossing technique can be performed in a manner that does not, in itself, cause gingival bleeding. This can perhaps assist in increasing the amount of people with bleeding disorders that floss, diminishing the fear that many people with bleeding disorders have of causing excessive bleeding with flossing.

Objective:

To evaluate the impact of interventions in a focused home infusion/specialty pharmacy based inhibitor management program on patient outcomes including, adherence, retention, prescriber communication.

Methods:

From our bleeding disorders patients’ databases between April 1, 2013 and March 31, 2014 (12 month period), prescriptions and assessment records were analyzed for patients with hemophilia A or B with inhibitors and those with acquired inhibitors. 49 unique patient records were reviewed, care managers were interviewed, and interventions were highlighted.

Results:

44 patients had Hemophilia A with an inhibitor, 2 had an inhibitor to Hemophilia B and 3 had acquired hemophilia. Hemophilia A patients had a diagnosis of severe hemophilia A (39), Moderate (2), Mild (2). 1 Hemophilia B patient was severe and the other moderate. Total number of active inhibitor patients on service (with a detectable Bethesda Unit titre) increased from 22 to 30 over this same period. 8 patients left service during the year due to insurance changes (4), and transfer to HTC’s 340B program (4). At the beginning of the study period, a multidisciplinary inhibitor management team (HTC experienced RN’s, RPh, SW, PT, Patient Advocate, and Hispanic Coordinator) was assembled and goals and processes for patient review and intervention were established. Monthly and ad hoc patient review meetings were implemented. Multiple barriers to adherence were encountered including immigration issues, language barriers, transportation issues, potential for caregiver burnout, storage and security of product concerns, relocations, product allergies, and needle phobia. Team worked collaboratively with HTC and other prescribers to intervene successfully in these issues. Interventions included long term twice daily nursing, securing an immigration attorney, hemophilia experienced translators, social worker, and physical therapist interventions, links to foundations for financial support, product bridge for insurance lapses, lab monitoring and reporting to HTC for remote patients, obtaining equipment (locking refrigerator) and protective supplies/ cooling compression cuffs. 30 patients received immune tolerance therapy during the study period. Of these, 25 were treated by an HTC and 5 were not. 10 patients on ITI achieved an “undetectable” inhibitor status during the study period. 8 were followed by an HTC and 2 were not. No patients were lost to therapy/management. All patients maintained positive interactions with prescribers and follow up visits.

Conclusion:

Inhibitor patients can be very challenging to manage. A focused, multidisciplinary inhibitor management team can extend the comprehensive model to the home, promote patient/prescriber/treatment team collaboration, and target interventions that enhance outcomes.

Introduction:

Extended half-life factor VIII (FVIII) products currently in development require a careful evaluation of dosing options given that the pharmacokinetics of weekly FVIII levels , including FVIII peak and trough levels, have been shown to play a role in bleeding occurrence.

Methods:

Pharmacokinetic (PK) modeling was conducted using published literature and clinical trial data. Published population PK models for recombinant full length DNA, plasma and albumin free FVIII (octocog alfa, rAHF-PFM) and recombinant B-domain-deleted FVIII Fc fusion product (efraloctocog alfa, rFVIIIFc) were used. All calculations were performed assuming linear pharmacokinetics. Dosing frequencies assessed were every 2 days with rAHF-PFM and every 3, 4, 5 or 7 days with rFVIIIFc. Dosages assessed were 30 IU/kg of rAHF-PFM and 30, 40, 50 or 65 IU/kg of rFVIIIFc. Results were generated for a hypothetical patient aged 30 years, with 70 kg body weight, exhibiting a VWF level of 118 IU/dL and a hematocrit of 45%. Time spent below 1% and 3% per week and time spent above 10% and 20% per week were assessed and compared for each scenario.

Summary:

Compared to 30 IU/kg of rAHF-PFM dosed every other day, a patient on rFVIIIFc would spend more time per week below 1% FVIII level when dosed every 5th day up to 50 IU/kg and when dosed every 7th day at any dose within the range tested. Moreover, even when increasing the dosing frequency to 30 IU/kg of rFVIIIFc every 3rd day, or when dosing rFVIIIFc up to 65 IU/Kg every 4th, 5th and 7th day the patient’s plasma FVIII level will drop below 3%. When looking at time per week spent above higher FVIII levels, the model patient would spend more time above 10% when dosed with rAHF-PFM at 30 IU/kg every second day as compared to rFVIIIFc dosed every 3 days at 30IU/kg, and every 4, 5 and 7 days at any dose within the range tested (≤65 IU/kg). Likewise, this patient will also spend more time above 20% with rAHF-PFM every other day than with rFVIIIFc dosed every 4 days at 40 IU/kg and every 5 days at 50 IU/kg and every 7 days at 65 IU/Kg.

Conclusion:

These data indicate that choice and optimal dosing of FVIII products require a better understanding of individual pharmacokinetics in order to avoid that patients would spend extended time at levels insufficient to protect them from bleeding, particularly subjects with a more active lifestyle.

Introduction and Objective:

Prospective clinical trials have demonstrated the efficacy of prophylaxis in reducing bleeding episodes in hemophilia A and B patients and those with inhibitors. However, data, predominantly from observational studies, have suggested more equivocal effects on health-related quality of life (HRQoL) [Buchbinder 2013]. The present review examined the impact of prophylaxis on HRQoL as measured during prospective trials.

Methods:

We conducted a systematic literature review of prospective studies evaluating the efficacy of prophylaxis in hemophilia using factor VIII, factor IX, or bypassing agents. Applying the inclusion criteria, we selected studies which evaluated HRQoL via validated instruments and summarized key data.

Results:

A total of 12 studies (hemophilia A [n=7]; hemophilia B [n=2]; inhibitors [n=3]) met all inclusion criteria and were reviewed. Of these studies, the investigational products were Advate (n=2), Kogenate (n=2), NovoEight (n=2), Eloctate (n=1), Rixubis (n=1), Aprolix (n=1), Feiba (n=2), and NovoSeven (n=1). HRQoL was assessed using one or a combination of the following instruments: SF-36 (n=3), EQ-5D (n=5), Haemo-QoL (n=2), Haem-A-QoL (n=3), Haemo-QOL-A (n=2) and general pain VAS (n=1). Seven of the 12 studies reported significant improvement in ≥1 HRQoL measure following prophylaxis. Advate, Rixubis and Feiba prophylaxis (among good responders with ≥ 50% bleed reduction) demonstrated statistically significant and clinically meaningful improvement in the physical component and certain domain(s) scores of the SF-36 (Valentino 2012; Windyga 2013; Gringeri 2013). Additionally, prophylaxis with Feiba showed clinically meaningful and/or statistically significant improvements in HRQoL (EQ-5D, Haemo-A-QoL), general health status (EQ-VAS) and general pain scores (VAS) (Antunes 2014; Stasyshyn 2014). Although, a previous Kogenate study indicated non-significant change in HRQoL measures (Collins 2003), recently published results from the SPINART trial demonstrated statistically significant and clinically meaningful improvement in several domains of the Haemo-QoL-A (Hong 2014). Prophylaxis with Eloctate and Alprolix resulted in non-significant change in the HRQoL measures used in their respective trials (Wyrwich 2013). Statistical and clinical significance were not reported for prophylaxis treatment with NovoEight (Santagostino 2014). Prophylaxis with NovoSeven showed a non-significant trend towards improvement in all dimensions of the EQ-5D but statistical improvement in general health status (EQ-VAS) (Hoots 2008).

Conclusion:

Results from Advate, Kogenate, Rixubis and Feiba trials offer robust evidence of clinically and statistically significant improvement in HRQoL in hemophilia patients treated with prophylaxis.

Introduction and Objective:

Limited information exists in the recent literature capturing real- world utilization and cost of bypassing agents among hemophiliac patients with inhibitors in the US. The present study compared the cost of on-demand and prophylaxis treatment between aPCC and rFVIIa among inhibitor patients with severe hemophilia.

Methods:

A retrospective analysis of two large US specialty pharmacy databases was conducted using dispensing data over a 28-month period (Jan. 2012 to April 2014). Subjects were included if they had a diagnosis of hemophilia A or B (ICD-9 code 286.0 or 286.1) that was classified as severe and ≥12 months of consecutive prescription claims for only bypassing agents. For patients who switched between bypassing agents or between on- demand (OD) and prophylaxis (P) during the observation period, observations of ≥6 months with consistent prescriptions were selected and analyzed independently. Bypassing agent utilization was annualized and normalized by patient weight (kg). Cost was calculated using 2013 Redbook® US wholesale acquisition costs (aPCC=$1.81/U and rFVIIa=$1.77/μg) and compared by product and regimen using non-parametric statistics.

Results:

A total of 78 subjects with 84 observations met the inclusion criteria. Median age was 20 years old (range 2-64) and median time between the first and last prescription filled was 20.5 months. Approximately 34.5% of the subjects were on aPCC (44.8% [OD] and 55.2% [P]) and 40.5% were on rFVIIa (85.3% [OD] and 14.7% [P]). The remaining subjects (25%) were on various combinations of aPCC and rFVIIa. Median annualized utilization for aPCC and rFVIIa was 7,183U/kg (2,186U/kg [OD] and 9,612U/kg [P]) and 13,838μg/kg (9,493μg/kg [OD] and 27,245μg/kg [P]), respectively. Median annualized cost/kg was significantly lower (p=0.0071) among patients treated on-demand with aPCC ($3,956/kg) compared to rFVIIa ($16,801/kg). Similarly, median annualized cost/kg was also significantly lower (p=0.0093) among patients treated prophylactically with aPCC ($17,399/kg) compared to rFVIIa ($48,223/kg). Overall, median annualized cost/kg for on-demand and prophylaxis treatments was 76.5% and 63.9% lower, respectively, with aPCC compared to rFVIIa. Furthermore, there was no significant difference (p=0.6438) in median annualized cost/kg between aPCC prophylaxis and rFVIIa on-demand.

Conclusion:

Overall, these data suggest that the annualized treatment cost with aPCC is significantly lower compared to that of rFVIIa for both on-demand and prophylaxis regimens. For each patient treated on-demand or prophylactically with rFVIIa, approximately 3-4 patients could be treated with aPCC at comparable cost. Additionally, the median rFVIIa on- demand patient could be prescribed aPCC prophylactically to reduce bleeding episodes without significant cost implications.

Objective:

Knowledge gaps among clinicians regarding diagnosis, classification, and/or management in hemophilia can potentially delay diagnosis/referral and lead to adverse clinical outcomes. A study was undertaken to identify hemophilia clinical practice gaps among pediatricians.

Methods:

A global, hemophilia-specific continuing medical education-accredited clinical practice assessment survey was developed based on current evidence-based consensus guidelines and best practices, including guidelines from the National Hemophilia Foundation and the World Federation of Hemophilia. The assessment included both knowledge- and case -based, multiple-choice questions that healthcare providers completed confidentially on-line between March 21, 2014 and April 16, 2014. Areas such as appropriate triggers for initiating prophylaxis and use of physical therapy were assessed. Responses from pediatric providers were de-identified and aggregated prior to analyses.

Summary:

817 pediatricians (42% of total respondents) completed the survey, from the following locales: North America (29%), Asia (23%), Europe (16%), Middle East (13%), Africa (9%), Central/South America (6%), and Australia (3%). Academic (36%), private practice (26%), community hospital (24%), community clinic (9%), and hemophilia treatment center (1%) practice settings were identified. For most responses, the proportion of incorrect responses appeared to be consistent regardless of whether pediatricians indicated professional interaction with hemophilia patients (Group A: 60%) or not (Group B: 40%). Pediatrician knowledge gaps included (% incorrect responses): classification of severity of hemophilia (28% A v. 39% B; P=.0030); optimal use of prophylactic therapy, e.g., when to initiate (29% A v. 30% B; P=.83), at what dose (16% A v. 17% B; P=.93); likelihood of inhibitors (51% A v. 55% B; P=.14); and adolescent care, e.g., adherence (25% A v. 22% B; P=.33), transitioning (14% A v. 14% B; P=.36), and long-term prophylaxis (76% A v. 76% B; P=.68). Differences in correct responses were observed when comparing Australia, Europe, and North America versus Africa, Asia, Central/South America, and the Middle East on topics such as classification of severity of hemophilia (P<.0001) and when to initiate prophylaxis (P=.04), although knowledge gaps existed in both groups. A low level of confidence in ability to identify when to use prophylaxis was reported among 42% [95% CI: 40%-46%] of pediatricians. The top barriers to the administration of prophylaxis included cost and lack of availability of FVIII or FIX (41% and 26% for all respondents, respectively).

Conclusions:

Substantial knowledge gaps permeate pediatric clinical practice in the diagnosis and optimal care of hemophilia. Educational efforts tailored to the practice setting and geographic locales are warranted.