Perceptions of Endocrine Therapy in African-American Breast Cancer Survivors: Mixed Methods Study.

BACKGROUND: Although the incidence of breast cancer is lower in African-American women than in White women, African-American women have a decreased survival rate. The difference in survival rate may stem from poor endocrine therapy adherence, which increases breast cancer recurrence. Therefore, accessible and culturally sensitive interventions to increase endocrine therapy adherence are necessary. OBJECTIVE: The purpose of this concurrent convergent mixed methods study was to provide further data to guide the development of the proposed culturally sensitive mHealth app, STORY+ for African-American women with breast cancer. METHODS: We recruited 20 African-American women diagnosed with estrogen-positive breast cancer and currently prescribed endocrine therapy. We used a concurrent convergent data collection method to (1) assess the use of smartphones and computers related to health care and (2) identify foundational aspects to support endocrine therapy adherence for incorporation in a mobile health app. RESULTS: Overwhelmingly, the participants preferred using smartphones to using computers for health care. Communicating with health care providers and pharmacies was the most frequent health care use of smartphones, followed by exercise tracking, and accessing the patient portal. We identified 4 aspects of adherence to endocrine therapy and smartphone use for incorporation in app development. The factors that emerged from the integrated qualitative and quantitative data were (1) willingness to use, (2) side effects, (3) social connection, and (4) beliefs about endocrine therapy. CONCLUSIONS: Further research is needed to develop a culturally sensitive app for African-American women with breast cancer to improve adherence to endocrine therapy. Our work strongly suggests that this population would use the app to connect with other African-American breast cancer survivors and manage endocrine therapy.

Consequences to patients, clinicians, and manufacturers when very serious adverse drug reactions are identified (1997-2019): A qualitative analysis from the Southern Network on Adverse Reactions (SONAR).

BACKGROUND: Adverse drug/device reactions (ADRs) can result in severe patient harm. We define very serious ADRs as being associated with severe toxicity, as measured on the Common Toxicity Criteria Adverse Events (CTCAE)) scale, following use of drugs or devices with large sales, large financial settlements, and large numbers of injured persons. We report on impacts on patients, clinicians, and manufacturers following very serious ADR reporting. METHODS: We reviewed clinician identified very serious ADRs published between 1997 and 2019. Drugs and devices associated with reports of very serious ADRs were identified. Included drugs or devices had market removal discussed at Food and Drug Advisory (FDA) Advisory Committee meetings, were published by clinicians, had sales > $1 billion, were associated with CTCAE Grade 4 or 5 toxicity effects, and had either >$1 billion in settlements or >1,000 injured patients. Data sources included journals, Congressional transcripts, and news reports. We reviewed data on: 1) timing of ADR reports, Boxed warnings, and product withdrawals, and 2) patient, clinician, and manufacturer impacts. Binomial analysis was used to compare sales pre- and post-FDA Advisory Committee meetings. FINDINGS: Twenty very serious ADRs involved fifteen drugs and one device. Legal settlements totaled $38.4 billion for 753,900 injured persons. Eleven of 18 clinicians (61%) reported harms, including verbal threats from manufacturer (five) and loss of a faculty position (one). Annual sales decreased 94% from $29.1 billion pre-FDA meeting to $4.9 billion afterwards (p<0.0018). Manufacturers of four drugs paid $1.7 billion total in criminal fines for failing to inform the FDA and physicians about very serious ADRs. Following FDA approval, the median time to ADR reporting was 7.5 years (Interquartile range 3,13 years). Twelve drugs received Box warnings and one drug received a warning (median, 7.5 years following ADR reporting (IQR 5,11 years). Six drugs and 1 device were withdrawn from marketing (median, 5 years after ADR reporting (IQR 4,6 years)). INTERPRETATION: Because very serious ADRs impacts are so large, policy makers should consider developing independently funded pharmacovigilance centers of excellence to assist with clinician investigations. FUNDING: This work received support from the National Cancer Institute (1R01 CA102713 (CLB), https://www.nih.gov/about-nih/what-we-do/nih-almanac/national-cancer-institute-nci; and two Pilot Project grants from the American Cancer Society's Institutional Grant Award to the University of South Carolina (IRG-13-043-01) https://www.cancer.org/ (SH; BS).

Improving oncology biosimilar launches in the EU, the USA, and Japan: an updated Policy Review from the Southern Network on Adverse Reactions.

The EU, the USA, and Japan account for the majority of biological pharmacotherapy use worldwide. Biosimilar regulatory approval pathways were authorised in the EU (2006), in Japan (2009), and in the USA (2015), to facilitate approval of biological drugs that are highly similar to reference products and to encourage market competition. Between 2007 and 2020, 33 biosimilars for oncology were approved by the European Medicines Agency (EMA), 16 by the US Food and Drug Administration (FDA), and ten by the Japan Pharmaceuticals and Medical Devices Agency (PMDA). Some of these approved applications were initially rejected because of manufacturing concerns (four of 36 [11%] with the EMA, seven of 16 [44%] with the FDA, none of ten for the PMDA). Median times from initial regulatory submission before approval of oncology biosimilars were 1·5 years (EMA), 1·3 years (FDA), and 0·9 years (PMDA). Pharmacists can substitute biosimilars for reference biologics in some EU countries, but not in the USA or Japan. US regulation prohibits substitution, unless the biosimilar has been approved as interchangeable, a designation not yet achieved for any biosimilar in the USA. Japan does not permit biosimilar substitution, as prescribers must include the product name on each prescription and that specific product must be given to the patient. Policy Reviews published in 2014 and 2016 in The Lancet Oncology focused on premarket and postmarket policies for oncology biosimilars before most of these drugs received regulatory approval. In this Policy Review from the Southern Network on Adverse Reactions, we identify factors preventing the effective launch of oncology biosimilars. Introduction to the market has been more challenging with therapeutic than for supportive care oncology biosimilars. Addressing region-specific competition barriers and educational needs would improve the regulatory approval process and market launches for these biologics, therefore expanding patient access to these products in the EU, the USA, and Japan.

End of an era of administering erythropoiesis stimulating agents among Veterans Administration cancer patients with chemotherapy-induced anemia.

Erythropoisis stimulating agent (ESA) use was addressed in Food and Drug Administration (FDA) Oncology Drug Advisory Committee (ODAC) meetings between 2004 and 2008. FDA safety-focused regulatory actions occurred in 2007 and 2008. In 2007, black box warnings advised of early death and venous thromboembolism (VTE) risks with ESAs in oncology. In 2010, a Risk Evaluation Strategies (REMS) was initiated, with cancer patient consent that mortality and VTE risks were noted with ESAs. We report warnings and REMS impacts on ESA utilization among Veterans Administration (VA) cancer patients with chemotherapy-induced anemia (CIA). Data were from Veterans Affairs database (2003-2012). Epoetin and darbepoetin use were primary outcomes. Segmented linear regression was used to estimate changes in ESA use levels and trends, clinical appropriateness, and adverse events (VTEs) among chemotherapy-treated cancer patients. To estimate changes in level of drug prescription rate after policy actions, model-specific indicator variables as covariates based on specific actions were included. ESA use fell by 95% and 90% from 2005, for epoetin and darbepoetin, from 22% and 11%, respectively, to 1% and 1%, respectively, among cancer patients with CIA, respectively (p<0.01). Following REMS in 2010, mean hematocrit levels at ESA initiation decreased from 30% to 21% (p<0.01). Black box warnings preceded decreased ESA use among VA cancer patients with CIA. REMS was followed by reduced hematocrit levels at ESA initiation. Our findings contrast with privately- insured and Medicaid insured cancer patient data on chemotherapy-induced anemia where ESA use decreased to 3% to 7% by 2010-2012. By 2012, the era of ESA administration to VA to cancer patients had ended but the warnings remain relevant and significant. In 2019, oncology/hematology national guidelines (ASCO/ASH) recommend that cancer patients with chemotherapy-induced anemia should receive ESAs or red blood cell transfusions after risk-benefit evaluation.

End of an era for erythropoiesis-stimulating agents in oncology.

Erythropoiesis-stimulating agents (ESAs) are available to treat chemotherapy-induced anemia (CIA). In 2007-2008, regulatory notifications advised of venous thromboembolism and mortality risks while the Center for Medicare and Medicaid Services' restricted ESA initiation to patients with hemoglobin <10 g/dl. In 2010, a Risk Evaluation and Mitigation Strategies required consent prior to administration. We evaluated ESA utilization from 2003 to 2012 and obtained private health insurer claims data for persons with lung, colorectal, or breast cancer from 2001 to 2012. ESA use for CIA was determined by an ESA claim after chemotherapy, up to 6 months after treatment. We identified 839,948 commercially insured patients, including 24,785 patients with ESA-treated CIA (3.2%). Darbepoetin use increased 3.9-fold from 2003 to 2007 (12.3% to 48.7%) and then decreased 95% to 2.6% by 2012. Epoetin use decreased 90% from 2003 to 2012 (30.3% to 3.1%). Between 2003 and 2012, mean epoetin dosing decreased 0.8-fold (244,979 in 2003 vs. 196,216 units in 2012), but increased 1.8-fold for darbepoetin-treated CIA (262 in 2003 to 467 µg in 2012). Among CIA patients, transfusions were low (4.5%) in 2002-2007, then increased 2.2-fold between 2008 and 2012. Safety initiatives between 2007 and 2010 facilitated reductions in ESA use combined with changes in coverage. These data show the efficacy of regulatory efforts, publication of adverse events and changes in reimbursement in reducing use of ESAs. Future studies are warranted to optimize deimplementation strategies to improve patient safety.

Caveat Medicus: Clinician experiences in publishing reports of serious oncology-associated adverse drug reactions.

Oncology-associated adverse drug/device reactions can be fatal. Some clinicians who treat single patients with severe oncology-associated toxicities have researched case series and published this information. We investigated motivations and experiences of select individuals leading such efforts. Clinicians treating individual patients who developed oncology-associated serious adverse drug events were asked to participate. Inclusion criteria included having index patient information, reporting case series, and being collaborative with investigators from two National Institutes of Health funded pharmacovigilance networks. Thirty-minute interviews addressed investigational motivation, feedback from pharmaceutical manufacturers, FDA personnel, and academic leadership, and recommendations for improving pharmacovigilance. Responses were analyzed using constant comparative methods of qualitative analysis. Overall, 18 clinicians met inclusion criteria and 14 interviewees are included. Primary motivations were scientific curiosity, expressed by six clinicians. A less common theme was public health related (three clinicians). Six clinicians received feedback characterized as supportive from academic leaders, while four clinicians received feedback characterized as negative. Three clinicians reported that following the case series publication they were invited to speak at academic institutions worldwide. Responses from pharmaceutical manufacturers were characterized as negative by 12 clinicians. One clinician's wife called the post-reporting time the "Maalox month," while another clinician reported that the manufacturer collaboratively offered to identify additional cases of the toxicity. Responses from FDA employees were characterized as collaborative for two clinicians, neutral for five clinicians, unresponsive for negative by six clinicians. Three clinicians endorsed developing improved reporting mechanisms for individual physicians, while 11 clinicians endorsed safety activities that should be undertaken by persons other than a motivated clinician who personally treats a patient with a severe adverse drug/device reaction. Our study provides some of the first reports of clinician motivations and experiences with reporting serious or potentially fatal oncology-associated adverse drug or device reactions. Overall, it appears that negative feedback from pharmaceutical manufacturers and mixed feedback from the academic community and/or the FDA were reported. Big data, registries, Data Safety Monitoring Boards, and pharmacogenetic studies may facilitate improved pharmacovigilance efforts for oncology-associated adverse drug reactions. These initiatives overcome concerns related to complacency, indifference, ignorance, and system-level problems as barriers to documenting and reporting adverse drug events- barriers that have been previously reported for clinician reporting of serious adverse drug reactions.

Cloud-based multi-media systems for patient education and adherence: a pilot study to explore patient compliance with colonoscopy procedure preparation.

Technology based patient education and adherence approaches are increasingly utilized to instruct and remind patients to prepare correctly for medical procedures. This study examines the interaction between two primary factors: patterns of patient adherence to challenging medical preparation procedures; and the demonstrated, measurable potential for cloud-based multi-media information technology (IT) interventions to improve patient adherence. An IT artifact was developed through prior design science research to serve information, reminders, and online video instruction modules to patients. The application was tested with 297 patients who were assessed clinically by physicians. Results indicate modest potential (43.4% relative improvement) for the IT-based approach for improving patient adherence to endoscopy preparations. Purposively designed cloud-based applications hold promise for aiding patients with complex medical procedure preparation. Health care provider involvement in the design and evaluation of a patient application may be an effective strategy to produce medical evidence and encourage the adoption of adherence apps.

Tale of Two Erythropoiesis-Stimulating Agents: Utilization, Dosing, Litigation, and Costs of Darbepoetin and Epoetin Among South Carolina Medicaid-Covered Patients With Cancer and Chemotherapy-Induced Anemia.

PURPOSE: The US Food and Drug Administration (FDA) has approved epoetin and darbepoetin for chemotherapy-induced anemia (CIA). Approved epoetin and darbepoetin dosing schedules were three times per week and weekly, respectively, although off-label, less frequent scheduling was common. In 2004, 2007, and 2008, a US Food and Drug Administration Advisory Committees warned of risks associated with erythropoiesis-stimulating agents. During this period, lawsuits alleging illegal darbepoetin marketing practices have concluded, resulting in $1.1 billion in fines and settlements and one criminal conviction. No prior study, to our knowledge, has reported on the use of darbepoetin versus epoetin for CIA. METHODS: We evaluated the dosing, utilization, and costs of erythropoiesis-stimulating agents among 3,761 South Carolina Medicaid patients with CIA. RESULTS: Epoetin and darbepoetin utilization rates were 22% and 28% in 2003, 10% and 33% in 2007, and 3% and 7% in 2010, respectively. Mean per-patient per-administration epoetin and darbepoetin doses were 40,983 IU and 191 µg, respectively, in 2003 and 47,753 IU and 369 µg, respectively, in 2010. Mean monthly patient costs for epoetin and darbepoetin were $1,030 and $981, respectively, in 2003 and $932 and $1,352, respectively, in 2010. Epoetin use decreased steadily between 2002 and 2010; darbepoetin use increased steadily between 2003 and 2007 and then decreased steadily thereafter. Per-patient dosing of darbepoetin, but not epoetin, increased steadily between 2003 and 2010, and monthly per-patient epoetin costs decreased 3% while the per-patients costs of darbepoetin increased 30% between 2003 and 2010. CONCLUSION: To our knowledge, our findings are the first data reporting on epoetin versus darbepoetin use for CIA and support recently concluded lawsuits involving allegations of illegal marketing practices of the manufacturer of darbepoetin.

Mobile mammography: An evaluation of organizational, process, and information systems challenges.

The purpose of this case study was to evaluate the information systems, personnel, and processes involved in mobile mammography settings, and offer recommendations to improve efficiency and satisfaction among patients and staff. Data includes on-site observations, interviews, and an electronic medical record review of a hospital who offers both mobile and fixed facility mammography services to their community. The optimal expectations for the process of mobile mammography from multiple perspectives were defined as (1) patient receives mammogram the day of their visit, (2) patient has efficient intake process with little wait time, (3) follow-up is completed and timely, (4) site contact and van staff are satisfied with van visit and choose to schedule future visits, and (5) the MMU is able to assess its performance and set goals for improvement. Challenges that prevent the realization of those expectations include a low patient pre-registration rate, difficulty obtaining required physician orders, frequent information system downtime/Internet connectivity issues, ill-defined organizational communication/roles, insufficient site host/patient education, and disparate organizational and information systems. Our recommendations include employing a dedicated mobile mammography team for end-to-end oversight, mitigating for system connectivity issues, allowing for patient self-referrals, integrating scheduling and registration processes, and a focused approach to educating site hosts and respective patients about expectations for the day of the visit. The MMU is an important community resource; we recommend simple process improvements and information flow improvements to further enable the MMU׳s goals.