Outcome Measures and Statistical Analysis

Patient demographics and clinical characteristics, treatment patterns, bleeding events, and HRU were assessed for the overall population of patients with VWD and the subset of potentially prophylaxis-eligible patients with VWD during the baseline and study periods. The following treatments were included in this analysis: hemostatic treatments such as antifibrinolytic drugs (including tranexamic acid), desmopressin acetate injection (DDAVP), desmopressin acetate nasal spray, VWF replacement therapy (recombinant VWF [rVWF, vonicog alfa, VONVENDI (US)/VEYVONDI (Europe), Takeda Pharmaceuticals USA, Lexington, MA, USA] or plasma-derived antihemophilic factor/VWF complex concentrates), antihemophilic factor alone, and red blood cell transfusion. Also included were other concomitant VWD and comorbidity treatments such as anticoagulants, antidepressants, hormone treatments, iron therapy, and local hemostatic treatments. Treatment was categorized as either on-demand, defined as receipt of a VWD-related treatment within 2 days of a bleeding event, or perioperative management, defined as receipt of a VWD-related treatment within 2 days of a surgery/procedure to prevent or reduce bleeds. Although the proportion of patients receiving prophylaxis for VWD was assessed, no patients in the sample met the criteria for prophylaxis treatment, possibly because prophylaxis was not an approved indication for any of the licensed VWF products for VWD in the United States at the time of the study.

Bleeding events were described in terms of location of the bleed (ie, GI, intracranial, eye, HMB, epistaxis, joint, and other bleeds) and annualized bleeding rates (ABRs). New bleeds were defined as any bleed occurring in a different location >3 days after the last treatment or >3 days after the onset of a previous bleed if untreated. To be considered as on-demand treatment, treatment had to take place within 2 days of a bleed. Therefore, bleeds that occurred in the same location >3 days after the last treatment or previous untreated bleed were considered as new bleeds. Bleeds that occurred in a different location within 3 days after the previous bleed were also considered as new bleeds. Recurrent bleeds were defined as any bleed occurring in the same location within 3 days of the last treatment or within 3 days after the onset of the previous untreated bleed. The ABR was calculated for each patient as the number of new bleeding episodes during the baseline or study period annualized to 1 year.

A subset of each of the main cohorts with linked claims data available was identified for the HRU analysis. All-cause and VWD-related HRU outcomes (inpatient stays, emergency department visits, and outpatient visits) were assessed during the baseline period and the 6-month period after the index date. VWD-related HRU was defined as any visit with an ICD-9/10-CM code for VWD or a bleed.

Analyses were descriptive and exploratory in nature. Means and standard deviations (SDs) were reported for continuous variables; frequencies and percentages were reported for categorical variables. Analyses were conducted using R version 3.6.3 and SAS Enterprise Guide 7.1.