Pamela Berry’s research while affiliated with GlaxoSmithKline and other places

Pazopanib (Votrient) is an orally administered tyrosine kinase inhibitor that blocks VEGF receptors potentially serving as anti-angiogenic treatment for hereditary hemorrhagic telangiectasia (HHT). We report a prospective, multi-center, open-label, dose-escalating study [50 mg, 100 mg, 200 mg, and 400 mg], designed as a proof-of-concept study to demonstrate efficacy of pazopanib on HHT-related bleeding, and to measure safety. Patients, recruited at 5 HHT Centers, required ≥ 2 Curacao criteria AND [anemia OR severe epistaxis with iron deficiency]. Co-primary outcomes, hemoglobin (Hgb) and epistaxis severity, were measured during and after treatment, and compared to baseline. Safety monitoring occurred every 1.5 weeks. Seven patients were treated with 50 mg pazopanib daily. Six/seven showed at least 50% decrease in epistaxis duration relative to baseline at some point during study; 3 showed at least 50% decrease in duration during Weeks 11 and 12. Six patients showed a decrease in ESS of > 0.71 (MID) relative to baseline at some point during study; 3/6 showed a sustained improvement. Four patients showed > 2 gm improvement in Hgb relative to baseline at one or more points during study. Health-related QOL scores improved on all SF-36 domains at Week 6 and/or Week 12, except general health (unchanged). There were 19 adverse events (AE) including one severe AE (elevated LFTs, withdrawn from dosing at 43 days); with no serious AE. In conclusion, we observed an improvement in Hgb and/or epistaxis in all treated patients. This occurred at a dose much lower than typically used for oncologic indications, with no serious AE. Further studies of pazopanib efficacy are warranted. Electronic supplementary material The online version of this article (10.1007/s10456-018-9646-1) contains supplementary material, which is available to authorized users.

Objective A prospective, qualitative study was conducted to develop a patient‐reported outcome measure (PROM) for daily administration via electronic diary (eDiary) to assess the severity of nosebleeds in patients with hereditary hemorrhagic telangiectasia (HHT), in accordance with Food and Drug Administration (FDA) PROM guidance criteria. Methods Three expert clinicians who treat patients with HHT provided input during instrument development, which comprised: 1) Peer‐reviewed literature and instrument review; 2) Development of draft Nosebleed Diary items; 3a) Three rounds of qualitative interviews (two with a paper‐based diary, one with an eDiary) with patients with documented severe epistaxis related to HHT, for concept elicitation and cognitive debriefing; 3b) Face validity and translatability assessment; 3c) Patient evaluation of the usability and acceptability of the eDiary device; and 4) Preparation of the final Nosebleed eDiary and conceptual framework. Results No existing instruments were identified that evaluate HHT‐related nosebleed severity daily and meet FDA PROM guidance criteria. Frequency, duration, and/or speed of flow (i.e., intensity) were reported by most participants with HHT when asked to describe their nosebleed severity. The Nosebleed eDiary was refined based on 17 patient interviews, clinical expert input and the face validity and translatability assessment. The final four‐item eDiary was acceptable to patients with HHT. Conclusion The Nosebleed eDiary is “fit for purpose” to assess the severity of HHT‐related nosebleeds, and has established face and content validity. Further adaptation may be required for use in mild or moderate HHT populations. Psychometric testing to evaluate construct validity and reliability are recommended next steps. Level of Evidence 2c “Outcomes research”