Validation and clinical discovery demonstration of breast cancer data from a real-world data extraction platform.

Objective: To validate and demonstrate the clinical discovery utility of a novel patient-mediated, medical record collection and data extraction platform developed to improve access and utilization of real-world clinical data. Materials and Methods: Clinical variables were extracted from the medical records of 1011 consented patients with breast cancer. To validate the extracted data, case report forms completed using the structured data output of the platform were compared to manual chart review for 50 randomly-selected patients with metastatic breast cancer. To demonstrate the platform's clinical discovery utility, we identified 194 patients with early-stage clinical data who went on to develop distant metastases and utilized the platform-extracted data to assess associations between time to distant metastasis (TDM) and early-stage tumor histology, molecular type, and germline BRCA status. Results: The platform-extracted data for the validation cohort had 97.6% precision (91.98%-100% by variable type) and 81.48% recall (58.15%-95.00% by variable type) compared to manual chart review. In our discovery cohort, the shortest TDM was significantly associated with metaplastic (739.0 days) and inflammatory histologies (1005.8 days), HR-/HER2- molecular types (1187.4 days), and positive BRCA status (1042.5 days) as compared to other histologies, molecular types, and negative BRCA status, respectively. Multivariable analyses did not produce statistically significant results. Discussion: The precision and recall of platform-extracted clinical data are reported, although specificity could not be assessed. The data can generate clinically-relevant insights. Conclusion: The structured real-world data produced by a novel patient-mediated, medical record-extraction platform are reliable and can power clinical discovery.

Multimorbidity in Atherosclerotic Cardiovascular Disease and Its Associations With Adverse Cardiovascular Events and Healthcare Costs: A Real-World Evidence Study.

Background: Atherosclerotic cardiovascular disease (ASCVD) remains the leading cause of mortality and disability in the United States and worldwide. Objective: To assess the multimorbidity burden and its associations with adverse cardiovascular events (ACE) and healthcare costs among patients with ASCVD. Methods: This is a retrospective observational cohort study using Aetna claims database. Patients with ASCVD were identified during the study period (1/1/2018-10/31/2021). The earliest ASCVD diagnosis date was identified as the index date. Qualified patients were ≥18 years of age and had ≥12 months of health plan enrollment before and after the index date. Comorbid conditions were assessed using all data available within 12 months prior to and including the index date. Association rule mining was applied to identify comorbid condition combinations. ACEs and healthcare costs were assessed using all data within 12 months after the index date. Multivariable generalized linear models were performed to examine the associations between multimorbidity and ACEs and healthcare costs. Results: Of 223 923 patients with ASCVD (mean [SD] age, 73.6 [10.7] years; 42.2% female), 98.5% had ≥2, and 80.2% had ≥5 comorbid conditions. The most common comorbid condition dyad was hypertension-hyperlipidemia (78.7%). The most common triad was hypertension-hyperlipidemia-pain disorders (61.1%). The most common quartet was hypertension-hyperlipidemia-pain disorders-diabetes (30.2%). The most common quintet was hypertension-hyperlipidemia-pain disorders-diabetes-obesity (16%). The most common sextet was hypertension-hyperlipidemia-pain disorders-diabetes-obesity-osteoarthritis (7.6%). The mean [SD] number of comorbid conditions was 7.1 [3.2]. The multimorbidity burden tended to increase in older age groups and was comparatively higher in females and in those with higher social vulnerability. The increased number of comorbid conditions was significantly associated with increased ACEs and increased healthcare costs. Discussion: Extremely prevalent multimorbidity should be considered in the context of clinical decision-making to optimize secondary prevention of ASCVD. Conclusions: Multimorbidity was extremely prevalent among patients with ASCVD. Multimorbidity patterns varied considerably across ASCVD patients and by age, gender, and social vulnerability status. Multimorbidity was strongly associated with ACEs and healthcare costs.

Effectiveness of BNT162b2 BA.4/5 Bivalent COVID-19 Vaccine against Long COVID Symptoms: A US Nationwide Study.

BACKGROUND: Long COVID has become a central public health concern. This study characterized the effectiveness of BNT162b2 BA.4/5 bivalent COVID-19 vaccine (bivalent) against long COVID symptoms. METHODS: Symptomatic US adult outpatients testing positive for SARS-CoV-2 were recruited between 2 March and 18 May 2023. Symptoms were assessed longitudinally using a CDC-based symptom questionnaire at Week 4, Month 3, and Month 6 following infection. The odds ratio (OR) of long COVID between vaccination groups was assessed by using mixed-effects logistic models, adjusting for multiple covariates. RESULTS: At Week 4, among 505 participants, 260 (51%) were vaccinated with bivalent and 245 (49%) were unvaccinated. Mean age was 46.3 years, 70.7% were female, 25.1% had ≥1 comorbidity, 43.0% prior infection, 23.0% reported Nirmatrelvir/Ritonavir use. At Month 6, the bivalent cohort had 41% lower risk of long COVID with ≥3 symptoms (OR: 0.59, 95% CI, 0.36-0.96, p = 0.034) and 37% lower risk of ≥2 symptoms (OR: 0.63, 95% CI, 0.41-0.96, p = 0.030). The bivalent cohort reported fewer and less durable symptoms throughout the six-month follow-up, driven by neurologic and general symptoms, especially fatigue. CONCLUSIONS: Compared with unvaccinated participants, participants vaccinated with the bivalent were associated with approximately 40% lower risk of long COVID and less symptom burden over the six-month study duration.

Increasing Clinical Trial Participation of Black Women Diagnosed with Breast Cancer.

Despite racial disparities in breast cancer mortality, Black women remain underrepresented in clinical trials. In this mixed methods research, 48 Black women were engaged via focus group discussions and in-depth interviews to better understand the lived experience of women with breast cancer. The results of this qualitative study informed the development of a subsequent online survey to identify barriers, motivators, and other factors that influence decision-making by Black women diagnosed with breast cancer when considering clinical trial participation. Among the 257 Black survey participants, most (95%) were aware of clinical trials; of those, most viewed them as lifesaving (81%) and/or benefiting others (90%). Negative perceptions such as serious side effects (58%), not receiving real treatment (52%), or risk of potential harm (62%) were indicated. Barriers included financial expenses (49%), concerns that their condition could be made worse (29%), that they would receive a placebo (28%), or that treatment was unapproved (28%). Participants were more likely than their health care providers (HCPs) to initiate discussions of clinical trials (53% versus 33%), and 29% of participants indicated a need for more information about risks and benefits, even after having those conversations. The most trustworthy sources of information on clinical trials were HCPs (66%) and breast cancer support groups (64%). These results suggest that trusted communities are key for providing education on clinical trials. However, there is also a need for HCPs to proactively discuss clinical trials with patients to ensure that they are adequately informed about all aspects of participation.

Psychosocial Wellbeing among Patients with Breast Cancer during COVID-19.

The impact of coronavirus disease 2019 (COVID-19) on the wellbeing of breast cancer (BC) patients is not well understood. This study described psychosocial problems among these patients in the United States (US) during the COVID-19 pandemic. Data were collected from BC patients via an online self-report survey between 30 March-6 July 2021 to assess the prevalence of COVID-19 diagnosis history and potential depression, health-related quality of life, COVID-related stress, and financial toxicity. Patients with early-stage (eBC) and metastatic (mBC) disease were compared. Of 669 patients included in the analysis, the prevalence of COVID-19 diagnosis history (10.9% versus 7.7%) and potential depression (33.7% versus 28.3%) were higher in mBC than eBC patients. Patients with eBC (versus mBC) had higher scores on nearly all Functional Assessment of Cancer Therapy-Breast scales (all, p < 0.001). For the Psychological Impact of Cancer subscales measuring negative coping strategies, the emotional distress score was the highest (9.1 ± 1.8) in the overall sample. Comprehensive Score for Financial Toxicity scores were higher in eBC than in mBC patients (24.2 ± 11.3 vs. 21.3 ± 10.2, p < 0.001). Overall, the COVID-19-related stress score was highest for danger/contamination fears (8.2 ± 5.6). In conclusion, impairments to psychosocial wellbeing among patients during the pandemic were observed, particularly financial toxicity and poor mental health and emotional functioning, with greater problems among mBC patients.

A Study Design to Harmonize Patient-Reported Outcomes Across Data Sets.

PURPOSE: Using patient-reported outcomes (PROs) provides important insights from the patient's perspective and can be valuable to monitor and manage treatment-related adverse events during cancer treatment. Additionally, the digital administration of PROs (electronic PROs [ePROs]) provides real-time updates to clinical care teams on treatment-related symptoms in-between clinic visits. However, given the variability in the methodology and timing of the data collection, using and harmonizing these data across different systems remains challenging. Identifying data elements to capture and operating procedures for harmonization across ePRO tools will expedite efforts to generate relevant and robust data on use of ePRO data in clinical care. METHODS: Friends of Cancer Research assembled a consortium of project partners from key health care sectors to align on a framework for ePRO data capture across ePRO tools and assessment of the impact of ePRO data capture on patient outcomes. RESULTS: We identified challenges and opportunities to align ePRO data capture across ePRO tools and aligned on key data elements for assessing the impact of ePRO data capture on patient care and outcomes. Ultimately, we proposed a study protocol to leverage ePRO data for symptom and adverse event management to measure real-world effectiveness of ePRO tool implementation on patient care and outcomes. CONCLUSION: This work provides considerations for harmonizing ePRO data sets and a common framework to align across multiple ePRO tools to assess the value of ePROs for improving patient outcomes. Future efforts to interpret evidence and evaluate the impact of ePRO tools on patient outcomes will be aided by improved alignment across studies.

Financial Toxicity among Patients with Breast Cancer during the COVID-19 Pandemic in the United States.

This study reported the prevalence of financial distress (financial toxicity (FT)) and COVID-19-related economic stress in patients with breast cancer (BC). Patients with BC were recruited from the Ciitizen platform, Breastcancer.org, and patient advocacy groups between 30 March and 6 July 2021. FT was assessed with the COmprehensive Score for financial Toxicity (COST) instrument. COVID-19-related economic stress was assessed with the COVID-19 Stress Scale. Among the 669 patients, the mean age was 51.6 years; 9.4% reported a COVID-19 diagnosis. The prevalence rates of mild and moderate/severe FT were 36.8% and 22.4%, respectively. FT was more prevalent in patients with metastatic versus early BC (p < 0.001). The factors associated with FT included income ≤ USD 49,999 (adjusted odds ratio (adj OR) 6.271, p < 0.0001) and USD 50,000-USD 149,999 (adj OR 2.722, p < 0.0001); aged <50 years (adj OR 3.061, p = 0.0012) and 50-64 years (adj OR 3.444, p = 0.0002); living alone (adj OR 1.603, p = 0.0476); and greater depression severity (adj OR 1.155, p < 0.0001). Black patients (adj OR 2.165, p = 0.0133), patients with income ≤ USD 49,999 (adj OR 1.921, p = 0.0432), or greater depression severity (adj OR 1.090, p < 0.0001) were more likely to experience COVID-19-related economic stress. FT was common in patients with BC, particularly metastatic disease, during COVID-19. Multiple factors, especially lower income and greater depression severity were associated with financial difficulties during COVID-19.

Real-world Application of Racial and Ethnic Imputation and Cohort Balancing Techniques to Deliver Equitable Clinical Trial Recruitment.

Enhancing diversity and inclusion in clinical trial recruitment, especially for historically marginalized populations including Black, Indigenous, and People of Color individuals, is essential. This practice ensures that generalizable trial results are achieved to deliver safe, effective, and equitable health and healthcare. However, recruitment is limited by two inextricably linked barriers - the inability to recruit and retain enough trial participants, and the lack of diversity amongst trial populations whereby racial and ethnic groups are underrepresented when compared to national composition. To overcome these barriers, this study describes and evaluates a framework that combines 1) probabilistic and machine learning models to accurately impute missing race and ethnicity fields in real-world data including medical and pharmacy claims for the identification of eligible trial participants, 2) randomized controlled trial experimentation to deliver an optimal patient outreach strategy, and 3) stratified sampling techniques to effectively balance cohorts to continuously improve engagement and recruitment metrics.

Patient reported outcomes: Financial toxicity is a barrier to clinical trials and personalized therapy in cholangiocarcinoma.

PURPOSE: Numerous experimental and targeted therapies are under investigation for patients with cholangiocarcinoma (CCA). Objective health-related quality of life (HRQoL) data for patients receiving these therapies are limited. METHODS: Patients engaged in the Cholangiocarcinoma Foundation completed two validated HRQoL surveys: Functional Assessment of Cancer Therapy (FACT)-Hepatobiliary and COmprehensive Score for financial Toxicity (COST). RESULTS: Two hundred eight patients were included. Seventy-five percent had intrahepatic CCA and 57% underwent resection, of which 48% had disease recurrence. Twenty-two percent enrolled in a clinical trial and 80% underwent molecular profiling, of which 29% received targeted therapy. While patients enrolled in a clinical trial or received targeted therapy reported similar HRQoL compared to those who did not, they reported higher financial toxicity (p = 0.05 and p = 0.01, respectively). CONCLUSION: Enrollment in a clinical trial or receipt of targeted therapy do not affect a patient's physical, emotional, social, or functional well-being. However, patients report higher financial burden. These therapies are mainly offered in the advanced setting after significant financial strain has been endured and are often only available at large academic centers, creating a physical barrier to access. These findings underscore the need to increase availability and eliminate physical and financial barriers that threaten access and utilization of personalized and progressive therapies.

Oncologist and Patient Preferences for Attributes of CDK4/6 Inhibitor Regimens for the Treatment of Advanced/Metastatic HR Positive/HER2 Negative Breast Cancer: Discrete Choice Experiment and Best-Worst Scaling.

PURPOSE: To understand and compare preferences for dosing- and toxicity-related attributes associated with selective cyclin-dependent 4/6 kinase inhibitors regimens among US oncologists and patients. MATERIALS AND METHODS: Oncologists and patients with mBC participated in an internet-based survey that included a discrete choice experiment (DCE) and a best-worst scaling (BWS) exercise. For the DCE, participants chose between two hypothetical treatment profiles, each with seven attributes: risk of dose reduction due to adverse events (AEs), risk of diarrhea, risk of abdominal pain, need for electrocardiogram (ECG) monitoring to assess heart function, risk of Grade 3/4 neutropenia, dosing regimen, and dosing schedule. The BWS exercise assessed the relative prioritization of a larger set of 16 attributes. Hierarchical Bayesian models were used to estimate preference weights for each attribute level. RESULTS: Oncologists (N=209) and patients (N=304) rated risks of diarrhea (25% each) and Grade 3/4 neutropenia (20% and 24%, respectively) as the most important attributes for treatment choice. The risks of diarrhea and Grade 3/4 neutropenia were 1.8 to 2.3 times (oncologists: 25% and 20%, respectively vs 11%) and 2.4 to 2.5 times (patients: 25% and 24%, respectively vs 10%) higher in relative importance than the risk of dose reduction due to AEs. Oncologists placed greater importance on the risk of dose reduction due to AEs and the need for ECG monitoring, whereas patients placed greater importance on the risk of Grade 3/4 neutropenia (all, p<0.05). The BWS exercise results were largely consistent with those from the DCE. CONCLUSION: The risks of diarrhea and Grade 3/4 neutropenia were key drivers of both oncologist and patient preferences. Overall, the palbociclib + aromatase inhibitor (AI) profile was most preferred, due to its association with a lower risk of diarrhea and no ECG monitoring, compared with abemaciclib + AI and ribociclib + AI profiles, respectively.

Treatment of painful bone metastases in prostate and breast cancer patients with the therapeutic radiopharmaceutical rhenium-188-HEDP. Clinical benefit in a real-world study.

AIM: Rhenium-188-HEDP ((188)Re-HEDP) is an effective radiopharmaceutical for the palliative treatment of osteoblastic bone metastases. However, only limited data on its routine use are available and its effect on quality of life (QoL) has not been studied. Therefore, we evaluated the clinical benefit of (188)Re-HEDP in routine clinical care. PATIENTS AND METHODS: Prostate or breast cancer patients with painful bone metastases receiving (188)Re-HEDP as a routine clinical procedure were eligible for evaluation. Clinical benefit was assessed in terms of efficacy and toxicity. Pain palliation and QoL were monitored using the visual analogue scale (VAS), corrected for opioid intake, and the EORTC QLQ-C30 Global health status/QoL-scale. Thrombocyte and leukocyte nadirs were used to assess haematological toxicity. RESULTS: 45 and 47 patients were evaluable for pain palliation and QoL, respectively. After a single injection of (188)Re-HEDP, the overall pain response rate was 69% and mean VAS-scores decreased relevantly and significantly (p < 0.05). Repeated treatment resulted in similar pain response. The overall QoL response rate was 68% and mean Global health status/QoL-scores increased relevantly and significantly. Haematological side effects were mild and transient. CONCLUSION: The clinically relevant response on pain and quality of life and the limited adverse events prove clinical benefit of treatment with (188)Re-HEDP and support its use in routine clinical care. Its effectiveness appears comparable to that of external beam radiotherapy.

At the intersection of HIV/AIDS and cancer: a qualitative needs assessment of community-based HIV/AIDS service organizations.

Due to advances in treatment, persons living with human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) are living longer, but with aging, immune deficits, and lifestyle factors, they are at increased risk for cancer. This challenges community-based AIDS service organizations (ASOs) to address the growing cancer needs of persons living with HIV/AIDS (PLWHA). Community-based participatory research was applied to engage ASOs in exploring their capacities and needs for integrating cancer-focused programming into their services. Focus groups were conducted with a community advisory board (CAB) representing 10 community-based organizations serving PLWHA. Three 90-minute, serial focus groups were conducted with a mean number of seven participants. Topics explored CAB members' organizational capacities and needs in cancer prevention, detection, treatment, and survivorship. Transcript analyses identified six themes: (a) agencies have limited experience with cancer-focused programs, which were not framed as cancer specific; (b) agencies need resources and collaborative partnerships to effectively incorporate cancer services; (c) staff and clients must be educated about the relevance of cancer to HIV/AIDS; (d) agencies want to know about linkages between HIV/AIDS and cancer; (e) cancer care providers should be culturally competent; and (f) agencies see opportunities to improve their services through research participation but are wary. Agency capacities were strong in relationships with clients and cultural competency, a holistic view of PLWHA health, expertise in prevention activities, and eagerness to be on the cutting edge of knowledge. Cancer education and prevention were of greatest interest and considered most feasible, suggesting that future projects develop accordingly. These findings suggest a high level of receptivity to expanding or initiating cancer-focused activities but with a clear need for education and awareness building. Qualitative findings will inform a large quantitative survey to validate identified themes, which will be applied in developing interventions to assist ASOs in adopting or expanding cancer-focused activities.

Development and preliminary evaluation of a training workshop for the collection of patient-reported outcome (PRO) interview data by research support staff.

This paper describes the development and initial evaluation of a didactic curriculum to prepare research support staff with the core knowledge and skills required to collect patient-reported outcomes (PROs) via interviews. Research support staff members (N = 77) were recruited for eight separate workshops, each consisting of a didactic presentation followed by role-play scenarios with trained actors depicting common scenarios they may encounter as part of patient interaction. Trainees were observed and received feedback on their performance from trained facilitators and peers. In comparison to their pre-training assessment, trainees showed significant improvement in their confidence to conduct a research interview, handle a distressed participant, manage a wandering interview, ask participants sensitive questions, and handle irritated patients. Training research support staff in the effective collection of PROs via patient interviews can improve the confidence of these individuals in interacting with patients, which can ultimately lead to increased accuracy of data collection.

Improving communication of diagnostic radiology findings through structured reporting.

PURPOSE: To compare the content, clarity, and clinical usefulness of conventional (ie, free-form) and structured radiology reports of body computed tomographic (CT) scans, as evaluated by referring physicians, attending radiologists, and radiology fellows at a tertiary care cancer center. MATERIALS AND METHODS: The institutional review board approved the study as a quality improvement initiative; no written consent was required. Three radiologists, three radiology fellows, three surgeons, and two medical oncologists evaluated 330 randomly selected conventional and structured radiology reports of body CT scans. For nonradiologists, reports were randomly selected from patients with diagnoses relevant to the physician's area of specialization. Each physician read 15 reports in each format and rated both the content and clarity of each report from 1 (very dissatisfied or very confusing) to 10 (very satisfied or very clear). By using a previously published radiology report grading scale, physicians graded each report's effectiveness in advancing the patient's position on the clinical spectrum. Mixed-effects models were used to test differences between report types. RESULTS: Mean content satisfaction ratings were 7.61 (95% confidence interval [CI]: 7.12, 8.16) for conventional reports and 8.33 (95% CI: 7.82, 8.86) for structured reports, and the difference was significant (P < .0001). Mean clarity satisfaction ratings were 7.45 (95% CI: 6.89, 8.02) for conventional reports and 8.25 (95% CI: 7.68, 8.82) for structured reports, and the difference was significant (P < .0001). Grade ratings did not differ significantly between conventional and structured reports. CONCLUSION: Referring clinicians and radiologists found that structured reports had better content and greater clarity than conventional reports.

Are gold standard depression measures appropriate for use in geriatric cancer patients? A systematic evaluation of self-report depression instruments used with geriatric, cancer, and geriatric cancer samples.

PURPOSE: Geriatric issues in cancer are becoming prominent. Depression is a significant concern for both the elderly and patients with cancer, yet identifying depression in these patients is difficult and often leads to under-recognition. We conducted a systematic review to determine which depression instruments are appropriate for use in geriatric patients with cancer. METHODS: We identified the most commonly used self-report depression instruments. We then used the criteria established in the US Food and Drug Administration Draft Guidance on Patient-Reported Outcome Measures to determine the extent of validation evidence of these measures in geriatric cancer populations. Finally, we determined which instruments captured depressive symptoms that are common among elderly patients with cancer. RESULTS: Eight measures were selected as the most commonly used instruments. These were the Beck Depression Inventory-II, Brief Symptom Inventory-18, Center for Epidemiologic Studies-Depression Scale, Geriatric Depression Scale-15, Hospital Anxiety and Depression Scale, Patient Health Questionnaire-9, Profile of Mood States-Short Form, and Zung Self-Rating Depression Scale. Many have been validated for use with geriatric adults and patients with cancer; however, data addressing content validity and responder definition were lacking. To date, there is no validation information for geriatric patients with cancer. Furthermore, symptom profile analysis revealed that these measures do not identify many symptoms signaling depression in geriatric patients with cancer. CONCLUSION: The validation evidence for use of common depression instruments in geriatric patients with cancer is lacking. This, and the possibility that these measures may not assess common depressive symptoms in geriatric patients with cancer, questions the adequacy of these scales in this population.

Making cross-racial therapy work: A phenomenological study of clients' experiences of cross-racial therapy.

A phenomenological/consensual qualitative study of clients' lived experiences of cross-racial therapy was conducted to enhance our understanding of whether, how, and under what conditions race matters in the therapy relationship. The sample consisted of 16 racial/ethnic minority clients who received treatment from 16 White, European American therapists across a range of treatment settings. Participants who reported a satisfying experience of cross-racial therapy (n=8) were examined in relation to gender- and in most cases, race/ethnicity-matched controls (n=8) who reported an overall unsatisfying experience. Therapy satisfaction was assessed during the screening process and confirmed during the research interview. Therapy narratives were analyzed using consensual qualitative research to identify the client, therapist, and relational factors that distinguished satisfied from unsatisfied cases. Findings reveal substantial differences at the level of individual characteristics and relational processes, providing evidence of both universal (etic) as well as culture/context-specific (emic) aspects of healing relationships. Recommendations for facilitating positive alliance formation in cross-racial therapy are provided based on clients' descriptions of facilitative conditions in the therapy relationship.