Patient-Centered Outcomes Research Institute

Abstract This second addition of High-Quality Psychosocial Interventions Research, From Conception to Piloting to Population Based Trials is a comprehensive guide for junior and investigators new to psychosocial interventions who wish to conduct clinical trials on psychosocial treatments. This book offers practical guidance on the ethical and efficient conduct of these studies and covers a range of topics from including how to assemble and manage research teams, ethical considerations, and how to run clinical trials of psychosocial interventions, from proof of concept to pragmatic effectiveness. This updated edition builds on the first by discussing alternative trial designs and how to conduct safe and effective remote or digital clinical research. It is suitable for investigators at all career stages. Students and junior faculty will find it a valuable step-by-step resource for planning and executing their research, while more experienced researchers—particularly those new to psychosocial interventions or effectiveness research—will find selected chapters especially useful. Each chapter covers ethical management of psychosocial intervention research, considerations for diversity and health disparities, example data reporting and sharing tools, sample forms for partnering with industry, and sample budgets for the various types of clinical trials.

BackgroundPatients with metastatic breast cancer (MBC) experience significant quality-of-life decrements, but there are few supportive care interventions specifically designed for this group that significantly improve quality of life. Ecological momentary assessment (EMA) and related ecological momentary interventions (EMIs) may be particularly beneficial for patients with MBC. However, no studies have previously examined the use of EMIs in the context of metastatic cancer.ObjectiveThe purpose of this study was to qualitatively assess experiences with EMA and preferences for intervention content and mode among patients living with MBC, with an emphasis on EMIs.MethodsWomen with MBC (n=29) were recruited from a longitudinal, observational study of quality of life using an EMA design. In-depth qualitative interviews assessed participants’ perspectives on the EMA design, including its feasibility, acceptability, and relevance to participants’ MBC experiences. Guided by participants’ EMA data, the interviews also examined the impact of self-monitoring and possible interventions when patients reported high symptom burden and/or low quality of life. Interviews were audio-recorded, transcribed verbatim, and analyzed using open coding, axial coding, and selective coding. The codebook was developed by reviewing a randomly selected subset of transcripts (n=5) and creating inductive, data-driven codes using the raw data, which were deductively organized into overarching themes.ResultsParticipants were mainly White (17/29, 59%), heterosexual (23/29, 79%), currently working (17/29, 59%), and held at least a bachelor’s degree (17/29, 59%). Participants had been living with MBC for a median of 2.5 years (range 0.2‐16.6 years). Most were diagnosed with hormone receptor-positive (23/29, 79%) and HER2-negative (21/29, 72%) breast cancer. Qualitative analysis identified 5 major themes. The participants reflected on their reasons for enrolling in the study, including interest in study activities and giving back to the MBC community (theme 1: participant engagement). Most participants found the EMA format easy to complete, and they provided recommendations for improving the design of future studies, including altering the timing and frequency of questionnaires (theme 2: feedback on study design). While less common, some participants discussed how engaging with the EMA protocol altered their experiences or behaviors (theme 3: impact of self-monitoring). Participants also discussed their reactions to seeing their EMA data, including their mixed thoughts on real-time data sharing (theme 4: responses to data). Finally, participants suggested programs and resources to improve their overall quality of life, reflecting on their interest in real-time interventions and peer-to-peer support (theme 5: recommendations for future interventions).ConclusionsPatients with MBC are willing to use EMA methodologies for data collection on quality of life and are open to EMIs with varying content and formats. Given variations in daily functioning between and within patients, a just-in-time adaptive intervention framework may be well suited for this population.

Hereditary angioedema (HAE) is a rare, genetic condition characterized by recurrent, unpredictable tissue swelling attacks. Using patient-reported outcome (PRO) instruments, we evaluated the patient experience of HAE attack manifestations and what constitutes a meaningful change in those manifestations to support development of key endpoints in clinical trials for on-demand treatment (ODT) of HAE attacks. This non-interventional, mixed methods study included participants with HAE in the United States. During the quantitative phase, participants completed electronic PRO assessments including Angioedema syMptom Rating scAle (AMRA) and Patient Global Impression of Severity (PGI-S) and Change (PGI-C) for ≥ 1 HAE attack in real time. A subset participated in a qualitative interview within 1–2 weeks of attack resolution. The quantitative phase included 35 participants (74.3% female; 85.7% White), 20 of whom participated in the qualitative phase. Data collected from 98 non-upper-airway attacks and 35 upper-airway attacks, including laryngeal attacks (total = 133), indicated associations between PGI-S/-C scores and AMRA composite scores, change from baseline (CFB), and percentage CFB. When comparing different definitions of time to onset of symptom relief, PGI-C had greater sensitivity in detecting early symptom relief yet remained comparable to AMRA symptom relief endpoints. Interviews confirmed most participants understood the PROs and considered them relevant. By characterizing the patient experience with approved ODTs on HAE manifestations using various PROs (AMRA, PGI-C/S), these mixed methods findings may inform the inclusion of suitable PRO instruments, and selection and hierarchical structuring of PRO-based clinical endpoints, in future trials of ODTs for HAE attacks.

The spinocerebellar ataxia composite score (SCACOMS) comprises items from the functional Scale for the Assessment and Rating of Ataxia (f-SARA) and the Clinician Global Impression of Change (CGI-C). In the derivation of SCACOMS, weights reflecting 1-year responsiveness were assigned to each item using partial least squares (PLS) regression modeling. The current objective was to incorporate patient-feedback into the SCACOMS item weights, examine corresponding responsiveness of the composite scale, and discuss potential implications for future use. Item weights derived by PLS regression were compared to each item's relative importance as assigned by 16 patients with SCA during semi-structured interviews. SCACOMS item weights were adjusted using the following combinations: (1) 50/50 weighted combination of PLS and patient weights and (2) reducing the weight of CGI-C to 20% and averaging individual item weights obtained from each perspective. The 1-year mean to standard deviation ratios (MSDRs) for the resulting reweighted scales were compared, with larger MSDRs indicating greatest sensitivity to disease progression. The PLS-derived SCACOMS had the highest MSDR (0.99). When item weights were averaged across the two sources, the resulting MSDR was 0.91. When the weight of CGI-C was set to 20%, reflecting patient preferences for higher weights on the discrete symptoms, the MSDR was 0.79. This study took a novel approach to enhance the face validity of SCACOMS by incorporating patient feedback into the statistically optimized item weights. The result is the merging of objectively derived item weightings (reflecting optimal scale responsiveness) with patient-assigned relevance. While this update may increase the patient centricity of a composite measure, this comes at the expense of reduced sensitivity. This potential trade-off in sensitivity to detect change should be evaluated in the context of the composite measure's intended use.

Abstract Introduction: Many people with metastatic breast cancer (MBC) experience life-limiting side effects from MBC treatments, with most patients remaining on treatment indefinitely. While supportive medications are often used to mitigate toxicities, they may introduce additional side effects and financial cost. Individualized dosing, particularly dose reductions and frequency adjustments, is a strategy to improve tolerability with the goal of maintaining treatment efficacy. The objective of this study was to elicit MBC patient experiences with treatment toxicity, including dosing strategies and side effect management. Methods: As a follow up to a 2020 survey to characterize real-world experiences with dosing strategies (Loeser et al. 2024), the Patient-Centered Dosing Initiative (PCDI) conducted a new cross-sectional survey to elicit patient experiences and preferences related to toxicity management. The survey, distributed electronically to a convenience sample of people living with MBC in the United States, combined closed and open-ended questions. Recruitment occurred through support organization e-mail lists and newsletters, as well as closed social media groups. The survey included items associated with side effect management, knowledge and experiences of dose modifications, and supportive medication use among other topics. The survey opened April 14th 2025 and data were pulled on June 22nd for analysis, although data collection is still ongoing. Descriptive statistics, including frequency counts and percentages, were used to summarize participant responses. Associations between knowledge of dose modifications and care primarily by a breast specialist were evaluated using chi-squared tests. Results: As of the abstract submission, 340 responses were available for analysis. Surveyed patients reported all treatment drugs taken in the metastatic setting, including cytotoxic chemotherapy (35%), CDK 4/6 inhibitors (62%), HER2-targeted antibodies (24%), antibody-drug conjugates (23%), and PI3K pathway inhibitors (11%). Of the 26% who started an MBC drug at a lower dose, 69% reported that the oncologist initiated the conversation and 16% said they initiated it themselves. There was no statistically significant difference in who initiated the conversation based on whether the participant was primarily treated by a breast specialist or not (p=0.43). Overall, 57% of the respondents had their dose reduced due to side effects, whether they started at full or reduced dose, and 72% felt better on the lower dose. In addition, 27% of patients reported that their oncologist reduced the frequency of drug administration; 67% of these patients felt better with the reduced frequency. 88% of surveyed patients were aware that an MBC drug with significant side effects may have an approved dose reduction schedule. Further, 59% believed that the highest dose of a drug is not always more effective than a lower dose. Conclusions: Dose modifications are common among people with MBC, often driven by treatment toxicity and side effect management. Experiences with dose reductions did not significantly differ based on receiving care from a breast cancer specialist, suggesting broader awareness and acceptance of dose adjustments in patient and clinical communities. Notably, 83% of respondents reported starting on a lower dose, having the dose reduced, or both, indicating a need for further study into the efficacy of lower doses and for clinical trial designs in MBC that include multiple doses tested in later phases. Given that patients rarely initiated these conversations, further research is needed to understand barriers to discussing dose adjustments and to support more patient-clinician dialogue. Citation Format: A. Beumer, M. Carlson, J. Maues, J. Cowden, S. Walker, A. Veach, J. Collins, K. Shanahan, M. E. Burkard, K. Kalinsky, A. Bardia, H. Rugo, M. Lustberg, E. L. Papautsky, A. Arcuri, J. Brown, M. Roberson. Dose reductions in metastatic breast cancer patients: Frequency, strategies, and patient experience [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS2-03-17.

Congenital cytomegalovirus (cCMV) is the most common congenital infection worldwide. cCMV can result in long-term impairments such as hearing loss and developmental delay. The study objective was to understand the caregiver experience of cCMV and caregiver-reported perceptions of the experience for cCMV patients. This non-interventional, cross-sectional study interviewed 25 caregivers of patients (aged 4 months to 17 years) with confirmed cCMV in the United States. Semi-structured qualitative interviewing methods were used to elicit descriptions of cCMV symptoms and their impact on the patient as perceived by the caregiver. Separate questions assessed the caregiver burden of a patient with cCMV. Transcripts were analyzed using an iterative coding process to identify key concepts. All caregivers reported increased healthcare needs for their child with cCMV. Other caregiver-reported patient impacts spanned multiple domains including emotional, physical and social functioning, education and communication. For example, a child with cCMV-related communication/hearing difficulties experiencing sadness or social isolation, or with cCMV-related seizures resulting in worry or apprehension. The caregiver impacts of caring for a child with cCMV also covered multiple domains including emotional, role and social functioning, work, sleep, and family planning. Emotional functioning was considered the greatest impact by approximately half of caregivers. These results advance understanding of experiences related to cCMV for caregivers and caregiver-reported perceptions of the patient experience. This may help healthcare professionals improve routine clinical practice for families affected by cCMV. The results and conceptual model may also support the development of a disease-specific clinical outcome assessment tool. Cytomegalovirus is a common virus, usually mild in healthy adults, that can be passed to an unborn baby during pregnancy (congenital cytomegalovirus). Some babies born with congenital cytomegalovirus have long-term health problems, such as hearing loss or learning disabilities. This study interviewed 25 parents caring for children with congenital cytomegalovirus in the United States to explore the impact of the disease on the lives of patients and caregivers. Impacts of congenital cytomegalovirus on the children, as reported by the caregivers, included emotional (e.g., anxiety, fear, worry), physical (e.g., needing devices to assist hearing) or social effects (e.g., social withdrawal), or difficulties with education or communication. All caregivers reported emotional impacts such as feelings of shock, anxiety, and fear, sometimes lasting a long time as parents worried about potential future impacts of congenital cytomegalovirus on their child. These results help to understand the impacts of congenital cytomegalovirus on the lives of patients and their families.

Introduction:Limited research has longitudinally assessed quality of life (QoL) among patients with metastatic breast cancer (MBC) outside of therapeutic clinical trials. This study used ecological momentary assessment (EMA) to examine QoL in daily life.Methods:Patients with MBC completed 12 EMA surveys over 4 weeks. Surveys utilized a visual analog scale (0–100) to assess global QoL, symptom severity (depression, anxiety, pain, fatigue, slowed cognitive functioning, appetite loss, nausea, gastrointestinal distress, decreased libido), and positive affect (social connection, peace, joy). Multilevel mixed-effects models analyzed the relationships between QoL and symptom severity and positive affect, when ratings differed across persons (between-person differences) and among the same person (within-person differences). We also explored longitudinal changes in QoL.Results:Participants (N=118; M=57.6 years old) were a mean of 4.3 years post-diagnosis. In mixed models adjusting for sociodemographic and health variables, between-subjects effects indicated QoL was worse among individuals who reported more depression (p=.009), more nausea (p=.005), and less joy (p<.001). Within-person effects indicated individuals’ QoL was lower when they reported worse depression (p<.001), anxiety (p=.012), and fatigue (p=.004), lower appetite (p=.019), lower libido (p=.018), and less social connectedness (p=.001), joy (p=.040), and peace (p<.001) than their average ratings. Mixed models estimated QoL was worse near diagnosis (p=.028), especially for patients who were older (p=.005) and non-partnered (p=.001).Conclusions:Both within-person and between-person variations in symptom severity and positive affect are associated with QoL. The relative influence of within-person variation suggests the need for adaptive, targeted intervention strategies to optimize patients’ quality of life.

Abstract BACKGROUND Salvage therapies for adults with recurrent ependymoma are limited. A prior retrospective review of patients with recurrent ependymoma treated with bevacizumab and carboplatin reported a 75% radiographic response rate. This prospective single arm, open label Phase 2 study was designed to confirm these results. METHODS 22 patients were evaluated in this CERN Adult Clinical Trials network study. Adult patients (age≥18) with recurrent ependymoma were treated with both carboplatin (AUC = 5 -6) every 4 weeks and bevacizumab 10mg/kg every 2 weeks for 6 cycles, after which carboplatin was discontinued, and bevacizumab could be continued at physician’s discretion. Imaging of areas involved by tumor, and patient reported outcomes with the MD Anderson Symptom Inventory questionnaires (brain and/or spine modules) were assessed at baseline and every 2 cycles to evaluate response and symptom burden, respectively. RESULTS With a median follow-up time of 25.9 months, the primary end point of 12-month progression free survival rate (PFS-12) greater than 50% was reached with a rate of 76.4% (95% CI, 52.2, 89.4). The median PFS of this cohort was 18.0 months. Two patients achieved a partial response (9.1%). There were no treatment-related grade 4 toxicities. Improved cognitive and neurological symptoms were observed in brain tumor responders, while spine tumor patients had worsening symptom outcomes regardless of response. CONCLUSIONS Treatment with carboplatin and bevacizumab in adult recurrent ependymoma reached the PFS-12 clinical efficacy threshold, suggesting that this treatment has efficacy in this patient population. However, symptomatic worsening in patients with spinal cord disease does raise concerns that bevacizumab pseudoresponse may account for some imaging stability and symptom improvement with brain disease.

Background: Direct oral anticoagulants (DOACs) are recommended for stroke prevention in patients with atrial fibrillation (AF); however, inappropriate dosages may increase risk for adverse events. Using data from the American Heart Association’s Get with the Guidelines-Stroke registry (GWTG-Stroke) linked with Medicare data, we evaluated the association of DOAC dosing with risk of stroke/systemic embolism, major bleeding, and all-cause mortality in older ischemic stroke patients with AF. Methods: We included ischemic stroke patients admitted to a GWTG-Stroke hospitals in Oct. 2012-Dec. 2019 who were &gt; 66 years, had a history of AF/flutter, and were discharged on a DOAC (dabigatran, rivaroxaban, or apixaban). DOAC dosing was defined as appropriate (standard dose or appropriately adjusted dose), underdose (reduced dose without indications for dose reduction or dose lower than recommended), or overdose (standard dose in patients with indications for dose reduction or dose higher than recommended). Normalized inverse probability weighted generalized boosted models were used to estimate 1-year outcomes after discharge. Results: Of the 37,464 ischemic stroke survivors (median age: 81 years; 53% female; 7% non-Hispanic Black), 68% were discharged with the appropriate DOAC dose, 22% were underdosed and 10% were overdosed. Apixaban was the most common DOAC (68%), followed by rivaroxaban (23%) and dabigatran (9%). The cumulative 1-year incidence of stroke/systemic embolism were 7.1%, 7.0%, and 7.9% among patients who were appropriate dosed, underdosed, and overdosed. After multivariable adjustments, there was no significant association between DOAC dose and stroke/systemic embolism ( Table ). However, patients who were overdosed (aHR 1.11 [1.01-1.23]) were associated with greater risk of major bleeding compared with appropriately dosed patients. Furthermore, patients who were underdosed were associated with greater risk of all-cause mortality (aHR 1.12 [1.06-1.18]). No significant association with mortality risk was observed in those who were overdosed. Conclusion: In a nationwide registry of ischemic stroke survivors with AF, approximately one-third of patients were prescribed a non-recommended DOAC dose. Patients who were overdosed had greater risk of major bleeding, while those underdosed had a greater risk of all-cause mortality. Strategies, including medical education, to ensure appropriate DOAC dosing at discharge are needed to reduce risk of adverse outcomes.

The MDS-UPDRS was not specifically developed for early-stage Parkinson’s disease (PD). This study investigated a sub-score of MDS-UPDRS Part III to assess bradykinesia and rigidity, which would be more targeted and clinically meaningful to assess disease progression in early-stage PD. A cross-sectional Rasch model was applied to the Parkinson’s Progression Markers Initiative (PPMI) untreated PD cohort data (N = 423) to define an adequate item set. Additionally, we evaluated how the daily life items from MDS-UPDRS Part II relate to bradykinesia and rigidity severity. A sub-score of 15 MDS-UPDRS Part III items focusing on limb-related bradykinesia and rigidity demonstrated good measurement properties in early-stage PD. Items adequately targeted to the study sample, and a meaningful hierarchy supported the validity of the scale. The scale was invariant to symptomatic treatment intake. Onset of clinical signs was represented as a milestone in the emergence of impairment in patients’ daily functioning.