PurposeTenosynovial giant cell tumor (TGCT), a rare locally aggressive neoplasm of the synovium of joints and tendon sheaths, is associated with joint destruction, inflammation, pain, and swelling, in part due to colony-stimulating factor 1 receptor–bearing macrophages recruited to the tumor by genetic elevation of colony-stimulating factor 1 activity. The most common treatment is surgery, although promising pharmacologic treatments are in development. Patient-reported outcome (PRO) instruments are critical end points in demonstrating the clinical relevance of standard oncologic outcome measures and the overall impact of novel pharmacologic therapies in nonmalignant neoplastic conditions such as TGCT. The content validity of PROs relevant to patients with TGCT has not been formally investigated, and instruments to evaluate such outcomes do not exist for this condition.MethodsPRO instruments of potential relevance were evaluated by using a literature review and by clinical and PRO experts. Patients with TGCT were recruited through clinical sites and the Internet for participation in qualitative research interviews to identify predominant symptoms and to test the relevance and content validity of several PRO measures. Select PRO measures were included in a Phase I clinical trial, and preliminary results of the PRO end points are reported descriptively.FindingsOf the 22 subjects who participated in qualitative interviews, 73% were female, and their mean age was 42.5 years (range, 27–56 years). The TGCTs (19 diffuse and 3 localized) were located in the knee (n = 15), hip (n = 3), ankle (n = 2), elbow (n= 1), and forearm (n = 1). The most common symptoms cited were pain (82%), swelling (86%), stiffness (73%), reduced range of motion (64%), and joint instability (64%), which were consistent with clinical expert input and with the content of instruments chosen by PRO experts. The worst pain numeric rating scale, Patient Reported Outcomes Measurement Information System physical functioning items, and the Western Ontario and McMaster Universities Osteoarthritis Index, as well as a worst stiffness numeric rating scale developed for TGCT, were confirmed as meaningful measures of TGCT patient symptoms and were well understood in qualitative interviews. Results from the Phase I trial showed trends of improvement in both pain and stiffness over time.ImplicationsThis study is the first to gather information directly from patients with TGCT regarding their symptom experiences. Pain, stiffness, and physical functioning are important treatment outcomes in patients with TGCT. We have identified content-valid PRO measures of these concepts, which are included in an ongoing Phase III TGCT clinical trial with pexidartinib (PLX3397) (NCT02371369).
BackgroundPerformance-based financing (PBF) both measures and determines payments based on the quality of care delivered and is emerging as a potential tool to improve quality.MethodsComparative case study methodology was used to analyze common challenges and lessons learned in quality of care across seven PBF programs (Democratic Republic of Congo, Kyrgyzstan, Malawi, Mozambique, Nigeria, Senegal and Zambia). The eight case studies, across seven PBF programs, compared were commissioned by the USAID-funded Translating Research into Action (TRAction) project (n = 4), USAID’s Health Finance and Government project (n = 3), and from the Global Delivery Initiative (n = 1).ResultsThe programs show similar design features to assess quality, but significant heterogeneity in their application. The seven programs included 18 unique quality checklists, containing over 1400 quality of care indicators, with an average per checklist of 116 indicators (ranging from 26-228). The quality checklists share a focus on structural components of quality (representing 80% of indicators on average, ranging from 38%-91%). Process indicators constituted an average of 20% across all checklists (ranging from 8.4% to 61.5%), with the majority measuring the correct application of care protocols for MCH services including child immunization. The sample included only one example of an outcome indicator from Kyrgyzstan. Performance data demonstrated a modest upward improvement over time in checklist scores across schemes, however, achievements plateaued at 60%-70%, with small or rural clinics reporting difficulty achieving payment thresholds due to limited resources and poor infrastructure. Payment allocations (distribution) and thresholds (for payments), data transparency, and approaches to measuring (verification) of quality differ across schemes.ConclusionsSimilarities exist in the processes that govern the design of PBF mechanisms, yet substantial heterogeneity in the experiences of implementing quality of care components in PBF programs are evident. This comparison suggests tailoring further the quality component of PBF programs to local and country contexts, and a need to better understand how quality is measured in practice. The growing operational experiences with PBF programs in different settings offer opportunities to learn from best practices, improve ongoing and future programs, and inform research to alleviate current challenges.
Background Three-dose series of conventional alum-adjuvanted Hepatitis B surface antigen (HBsAg)-based vaccines achieve seroprotection rates (SPRs) of 35-70% in PLWH. HepB-CpG, a HBsAg vaccine adjuvanted with a TLR-9 agonist, achieves high SPR in immunocompetent adults with a 2-dose regimen, but limited data exist in PLWH. Methods A5379 is an ongoing prospective, open-label study to evaluate immunogenicity of the HBV vaccine HepB-CpG in PLWH. The HBV vaccine-naïve group consisted of PLWH without past HBV infection on antiretroviral therapy with CD4 ≥100 cells/mm3 and HIV-1 RNA < 1000 copies/mL. Participants received 0.5 mL of HepB-CpG intramuscularly (20 mcg recombinant HBsAg and 3000 mcg of CpG 1018® adjuvant) at Wks 0, 4, and 24. Primary objectives were to determine the proportion of participants who achieve seroprotection (HBsAb≥10 mIU/mL) at Wk 28 and to assess safety. This study was designed to conclude SPR >55%, with up to 10% loss to follow-up prior to 28 wks. Results Of the 74 eligible participants enrolled at 13 global sites: 46% were male, 66% Asian, 16% Black,15% White and median age was 47 years (range 23-68). 27% were enrolled in the US, 65% in Thailand. Median CD4 was 625 cells/mm3, 96% had HIV-1 RNA < 60 copies/mL, and 9% had diabetes. Primary analysis set per analysis plan consisted of 68 participants (excluded: 3 missed visit, 3 out of visit window). All 68 completed 3 doses and achieved seroprotection (100% [95% CI: 94.7%, 100%]). 88% had HBsAb >1000 mIU/mL (assay upper limit). The SPR was also 100% [CI: 94.2%,100%] in the per protocol analysis set of 62 participants. At 8 wks after the 2nd dose, the SPR was 94.4% followed by 98.5% at Wk 24, prior to the 3rd dose. The proportion of participants with HBsAb >1000 mIU/mL increased from 27.9% at Wk 24 to 83.8% at Wk 28. One or more AEs related to study treatment were experienced by 61% of participants (39% Grade 1, 20% Grade 2, Grade 3 malaise in one participant). Vaccination site pain (40%), malaise (26%), fatigue (23%), myalgia (22%) and headache (22%) were the most frequent AEs. Seroprotection achieved by study week. Percentage of participants achieving seroprotection over the first 28 study weeks. HepB-CpG vaccine was administered at Entry, Week 4, and Week 24. Conclusion In this study of PLWH with no history of HBV vaccination or evidence of prior HBV exposure, 100% seroprotection was achieved at 4 weeks after 3 doses of the HepB-CpG. No unexpected safety issues were observed. Disclosures Kristen Marks, MD, MS, Gilead Sciences: Grant/Research Support Andrea L. Cox, M.D. Ph.D., Janssen: Advisor/Consultant Jennifer C. Price, MD, PhD, AbbVie: Grant/Research Support|Gilead Sciences: Grant/Research Support|Gilead Sciences: Honoraria|Merck: Grant/Research Support|Theratechnologies: Advisor/Consultant Kelvin McKoy, M.D., M.B.A., Dynavax Technologies: Employee|Dynavax Technologies: Ownership Interest|Dynavax Technologies: Stocks/Bonds Kenneth E. Sherman, MD, PhD, AbbVie: Grant/Research Support|Gilead: Advisor/Consultant|Gilead: Grant/Research Support|Helio: Grant/Research Support|Inovio: DSMB|Intercept: Grant/Research Support|MedPace: DSMB|Theratechnologies: Advisor/Consultant|Zydus: Grant/Research Support.
In this international, multicenter open-label study (ACTG A5379) of HepB-CpG vaccine in people with HIV without prior Hepatitis B Virus (HBV) vaccination, all 68 participants achieved HBV seroprotective titers after the 3-dose series in the primary analysis. No unexpected safety issues were observed.
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