How might improved estimates of HIV programme outcomes influence practice? A formative study of evidence, dissemination and response

BACKGROUND: While HIV programmes have started millions of persons on life-saving antiretroviral therapy in Africa, longitudinal health information systems are frail and, therefore, data about long-term survival is often inaccurate or unknown to HIV programmes. The \u27Better Information for Health in Zambia\u27 (BetterInfo) Study - a regional sampling-based survey to assess retention and mortality in HIV programmes in Zambia - found both retention and mortality to be higher than prevailing estimates from national surveillance systems. We sought to understand how Zambian health decision-makers at different health system levels would respond to these new data, with a view to informing research translation. METHODS: We interviewed 25 purposefully sampled health decision-makers from community, facility, district, provincial and national levels. During the interviews, we shared retention and mortality estimates from both routine programme surveillance and those generated by the study. Transcripts were analysed for inductive and deductive themes, the latter drawing on Weiss\u27s framework that policy-makers interpret and apply evidence as \u27warning\u27, \u27guidance\u27, \u27reconceptualisation\u27 or \u27mobilisation of support\u27. FINDINGS: All decision-makers found study findings relevant and important. Decision-makers viewed the underestimates of mortality to be a warning about the veracity and informativeness of routine data systems. Decision-makers felt guided by the findings to improve data monitoring and, acknowledging limitations of routine data, utilised episodic patient tracing to support improved data accuracy. Findings catalysed renewed motivation and mobilisation by national level decision-makers for differentiated models of HIV care to improve patient outcomes and also improved data management systems to better capture patient outcomes. Inductive analysis highlighted a programmatic application data interpretation, in which study findings can influence facility and patient-level decision-making, quality of care and routine data management. CONCLUSIONS: New epidemiological data on patient outcomes were widely seen as informative and relevant and can potentially catalyse health system action such as using evaluations to supplement electronic medical record data to improve HIV programmes. Formative evidence suggests that targeting research dissemination at different levels of the health system will elicit different responses. Researchers supporting the translation of evidence to action should leverage all relevant levels of the health system to facilitate both policy and programmatic action

How might improved estimates of HIV programme outcomes influence practice? A formative study of evidence, dissemination and response

Background While HIV programmes have started millions of persons on life-saving antiretroviral therapy in Africa, longitudinal health information systems are frail and, therefore, data about long-term survival is often inaccurate or unknown to HIV programmes. The 'Better Information for Health in Zambia' (BetterInfo) Study - a regional sampling-based survey to assess retention and mortality in HIV programmes in Zambia - found both retention and mortality to be higher than prevailing estimates from national surveillance systems. We sought to understand how Zambian health decision-makers at different health system levels would respond to these new data, with a view to informing research translation. Methods We interviewed 25 purposefully sampled health decision-makers from community, facility, district, provincial and national levels. During the interviews, we shared retention and mortality estimates from both routine programme surveillance and those generated by the study. Transcripts were analysed for inductive and deductive themes, the latter drawing on Weiss's framework that policy-makers interpret and apply evidence as 'warning', 'guidance', 'reconceptualisation' or 'mobilisation of support'. Findings All decision-makers found study findings relevant and important. Decision-makers viewed the underestimates of mortality to be a warning about the veracity and informativeness of routine data systems. Decision-makers felt guided by the findings to improve data monitoring and, acknowledging limitations of routine data, utilised episodic patient tracing to support improved data accuracy. Findings catalysed renewed motivation and mobilisation by national level decision-makers for differentiated models of HIV care to improve patient outcomes and also improved data management systems to better capture patient outcomes. Inductive analysis highlighted a programmatic application data interpretation, in which study findings can influence facility and patient-level decision-making, quality of care and routine data management. Conclusions New epidemiological data on patient outcomes were widely seen as informative and relevant and can potentially catalyse health system action such as using evaluations to supplement electronic medical record data to improve HIV programmes. Formative evidence suggests that targeting research dissemination at different levels of the health system will elicit different responses. Researchers supporting the translation of evidence to action should leverage all relevant levels of the health system to facilitate both policy and programmatic action

Epidemiology of interstitial lung disease in patients with metastatic breast cancer at baseline and after treatment with HER2-directed therapy: a real-world data analysis.

PURPOSE: Using real-world data, interstitial lung disease (ILD) prevalence before and after HER2-directed therapy was estimated. Potential ILD risk factors in patients receiving HER2-directed therapy for metastatic breast cancer (mBC) were evaluated. METHODS: Adults with HER2-directed therapy for mBC initiated between September 25, 1998, and February 22, 2020 were, included. ILD was defined broadly as one or more of 64 lung conditions. Patients were followed until incident ILD, death, last contact, or study end. RESULTS: In total, 533 patients were identified with median age at mBC of 57, 51% had de novo mBC, 43% were ever smokers, 30% had lung metastases, 9% had thoracic radiation, 6% had chronic obstructive pulmonary disease, and 16% had prevalent ILD. ILD cumulative incidence at one year was 9% (95% CI 6%, 12%), with a median follow-up of 23 months. Smoking (HR 2.2, 95% CI 1.1, 4.8) and Black/African-American race (HR 3.4, 95% CI 1.6, 7.5) were significantly associated with ILD; HRs for preexisting lung conditions (HR 1.8, 95% CI 0.9, 3.8) and thoracic radiation (HR 2.3, 95% CI 0.8, 7.1) were not statistically significant. Prevalent ILD was associated with 13-fold greater occurrence of incident ILD. 85% of patients with prevalent or incident ILD were symptomatic. CONCLUSIONS: This real-world population of patients with mBC had a high prevalence of ILD prior to HER2-directed therapy, reflecting the multifactorial causation of interstitial lung changes. The cumulative incidence of ILD in patients receiving HER2-directed therapy for mBC augments prior reports. Symptomatic presentation suggests an opportunity for early intervention

Real-World Treatment Patterns and Clinical Effectiveness of Palbociclib Plus an Aromatase Inhibitor as First-Line Therapy in Advanced/Metastatic Breast Cancer: Analysis from the US Syapse Learning Health Network

This retrospective single-arm study assessed real-world treatment patterns and clinical outcomes in patients with hormone receptor—positive/human epidermal growth factor receptor 2—negative (HR+/HER2−) advanced/metastatic breast cancer (A/MBC) who received palbociclib plus an aromatase inhibitor as first-line therapy in US community health systems. Using electronic health records from the Syapse Learning Health Network, 242 patients were identified as having received first-line palbociclib plus an aromatase inhibitor between 3 February 2015, and 31 July 2019 (data cutoff 1 February 2020) resulting in a minimum potential 6-month follow-up period. In total, 56.6% of patients had de novo A/MBC at initial breast cancer diagnosis, 50.8% had bone-only disease, and 32.2% had visceral disease. Median follow-up was 22.4 months. Disease progression (26.4%) and intolerance/toxicity (14.9%) were the main reasons for treatment discontinuation. The median (95% CI) real-world progression-free survival was 31.7 (27.9—not estimable (NE)) months and 2-year estimated overall survival (OS) rate was 78.0%. In total, 25.6% of patients died; however, OS data are limited by the small population size and insufficient follow-up time. These real-world effectiveness outcomes complement findings from other real-world studies and randomized controlled trials and support palbociclib plus an aromatase inhibitor as first-line therapy for HR+/HER2− A/MBC

Real-World Treatment Patterns and Clinical Effectiveness of Palbociclib Plus an Aromatase Inhibitor as First-Line Therapy in Advanced/Metastatic Breast Cancer: Analysis from the US Syapse Learning Health Network.

This retrospective single-arm study assessed real-world treatment patterns and clinical outcomes in patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) advanced/metastatic breast cancer (A/MBC) who received palbociclib plus an aromatase inhibitor as first-line therapy in US community health systems. Using electronic health records from the Syapse Learning Health Network, 242 patients were identified as having received first-line palbociclib plus an aromatase inhibitor between 3 February 2015, and 31 July 2019 (data cutoff 1 February 2020) resulting in a minimum potential 6-month follow-up period. In total, 56.6% of patients had de novo A/MBC at initial breast cancer diagnosis, 50.8% had bone-only disease, and 32.2% had visceral disease. Median follow-up was 22.4 months. Disease progression (26.4%) and intolerance/toxicity (14.9%) were the main reasons for treatment discontinuation. The median (95% CI) real-world progression-free survival was 31.7 (27.9-not estimable (NE)) months and 2-year estimated overall survival (OS) rate was 78.0%. In total, 25.6% of patients died; however, OS data are limited by the small population size and insufficient follow-up time. These real-world effectiveness outcomes complement findings from other real-world studies and randomized controlled trials and support palbociclib plus an aromatase inhibitor as first-line therapy for HR+/HER2- A/MBC

Molecular Biomarker Testing and Targeted Therapy Patterns in Patients with Acute Myelogenous Leukemia (AML) in Community Health Systems in the United States: A Real-World Data Analysis

Background and Objective: Molecular testing and treatment patterns for patients (pts) diagnosed with acute myelogenous leukemia (AML) have evolved over recent years. Next-generation sequencing (NGS) technologies allow for detection of somatic gene alterations that have prognostic and/or predictive/therapeutic significance. To describe the real-world testing patterns and clinical management of patients with AML, NGS testing, other molecular testing, mutations detected, and targeted treatment administration were analyzed in 2 large community health systems in the US. Methods: Pts \u3e18 years, diagnosed with AML from January 1, 2015 to December 31, 2020, were identified in the Syapse Learning Health Network, a real-world database with clinical and genomic data from integrated community delivery networks. Study end date was March 31, 2021, allowing for a minimum follow up of 3 months from diagnosis. Pts with less than 2 clinical encounters were excluded. Electronic health records were reviewed retrospectively to analyze molecular biomarker testing patterns, actionable and prognostic biomarkers detected as defined by NCCN guidelines version 3, 2021, and targeted treatments administered. This study received Institutional Review Board (IRB) exemption. Results: The study included 685 pts with median age at AML diagnosis of 70 and median follow up of 5.4 months. 55% were male, 73% were non-Hispanic white, 10% were non-Hispanic black, 31% had ECOG performance status (PS) 0 or 1 and 16% had ECOG PS \u3e 2 at diagnosis, and 69% had de novo AML. Pts with secondary AML consisted of pts evolving from prior myelodysplasia, myeloproliferative disorder, or aplastic anemia, or therapy related AML. 4% had favorable cytogenetic prognosis, 33% intermediate, and 30% adverse, with the remaining 33% unknown. 541 (79%) pts received either NGS or other molecular biomarker tests. 375 (55%) pts received NGS with or without other molecular biomarker tests and 166 (24%) pts received other molecular biomarker tests only [e.g. Sanger Sequencing, RT-PCR (reverse transcription polymerase chain reaction), PCR]. Pts who did not receive molecular biomarker testing (n=144) were older with median age of 78 and median follow-up of 2 months. There was no statistically significant difference in molecular biomarker testing received between non-Hispanic white and non-Hispanic black population (p=0.275) in the study. There was a statistically significant difference in molecular biomarker testing received between de novo (84% tested) and secondary (67% tested) AML (p=30 days after diagnosis), with 5% missing relevant dates. 294 (78%) pts had NGS performed on bone marrow aspirate. NGS testing rates rose from 9% of pts diagnosed with AML in 2015, to 77% of pts in 2020. Among pts who received molecular testing (n=541), the proportions of pts tested for specific prognostic and actionable biomarkers by year of diagnosis are found in figures 1 and 2. 204 (38%) pts who received molecular testing had an actionable biomarker detected and of those 204 pts, 70 (34%) received at least one targeted therapy. The proportion of pts with one or more actionable mutations (FLT3, IDH1, IDH2) who receive targeted therapy is presented in table 1 below. Conclusions: Real-world data provide insights into molecular testing and targeted therapy patterns in routine clinical practice. In this study, testing uptake has increased over time with most pts diagnosed in 2020 receiving testing for FLT3-TKD, FLT3-ITD, IDH1, IDH2 and NPM1. Testing uptake did not differ by race. Among pts with a documented actionable alteration, one third received a targeted therapy. These findings show progress in testing for pts with targetable biomarkers in AML in the community setting, although further increases in testing and faster results could provide additional clinical benefit. Future directions for this work include analyzing patient outcomes