Integrating 4 methods to evaluate physical function in patients with cancer (In4M): protocol for a prospective cohort study.

INTRODUCTION: Accurate, patient-centred evaluation of physical function in patients with cancer can provide important information on the functional impacts experienced by patients both from the disease and its treatment. Increasingly, digital health technology is facilitating and providing new ways to measure symptoms and function. There is a need to characterise the longitudinal measurement characteristics of physical function assessments, including clinician-reported outcome, patient-reported ported outcome (PRO), performance outcome tests and wearable data, to inform regulatory and clinical decision-making in cancer clinical trials and oncology practice. METHODS AND ANALYSIS: In this prospective study, we are enrolling 200 English-speaking and/or Spanish-speaking patients with breast cancer or lymphoma seen at Mayo Clinic or Yale University who will receive intravenous cytotoxic chemotherapy. Physical function assessments will be obtained longitudinally using multiple assessment modalities. Participants will be followed for 9 months using a patient-centred health data aggregating platform that consolidates study questionnaires, electronic health record data, and activity and sleep data from a wearable sensor. Data analysis will focus on understanding variability, sensitivity and meaningful changes across the included physical function assessments and evaluating their relationship to key clinical outcomes. Additionally, the feasibility of multimodal physical function data collection in real-world patients with breast cancer or lymphoma will be assessed, as will patient impressions of the usability and acceptability of the wearable sensor, data aggregation platform and PROs. ETHICS AND DISSEMINATION: This study has received approval from IRBs at Mayo Clinic, Yale University and the US Food and Drug Administration. Results will be made available to participants, funders, the research community and the public. TRIAL REGISTRATION NUMBER: NCT05214144; Pre-results.

Integrating 4 Measures to Evaluate Physical Function in Patients with Cancer (In4M): Protocol for a prospective study.

Introduction: Accurate, patient-centered evaluation of physical function in patients with cancer can provide important information on the functional impacts experienced by patients both from the disease and its treatment. Increasingly, digital health technology is facilitating and providing new ways to measure symptoms and function. There is a need to characterize the longitudinal measurement characteristics of physical function assessments, including clinician-reported physical function (ClinRo), patient-reported physical function (PRO), performance outcome tests (PerfO) and wearable data, to inform regulatory and clinical decision-making in cancer clinical trials and oncology practice. Methods and analysis: In this prospective study, we are enrolling 200 English- and/or Spanish-speaking patients with breast cancer or lymphoma seen at Mayo Clinic or Yale University who will receive standard of care intravenous cytotoxic chemotherapy. Physical function assessments will be obtained longitudinally using multiple assessment modalities. Participants will be followed for 9 months using a patient-centered health data aggregating platform that consolidates study questionnaires, electronic health record data, and activity and sleep data from a wearable sensor. Data analysis will focus on understanding variability, sensitivity, and meaningful changes across the included physical function assessments and evaluating their relationship to key clinical outcomes. Additionally, the feasibility of multi-modal physical function data collection in real-world patients with cancer will be assessed, as will patient impressions of the usability and acceptability of the wearable sensor, data aggregation platform, and PROs. Ethics and dissemination: This study has received approval from IRBs at Mayo Clinic, Yale University, and the U.S. Food & Drug Administration. Results will be made available to participants, funders, the research community, and the public. Registration Details: The trial registration number for this study is NCT05214144. Strengths & Limitations: This study addresses an important unmet need by characterizing the performance characteristics of multiple patient-centered physical function measures in patients with cancerPhysical function is an important and undermeasured clinical outcome. Scientifically rigorous capture and measurement of physical function constitutes a key component of cancer treatment tolerability assessment both from a regulatory and clinical perspective.This study will include patients with lymphoma or breast cancer receiving a broad range of cytotoxic chemotherapy regimens. While recruitment will occur at two academic sites, patients who ultimately receive treatment at local community sites will be included.A patient-centered health data aggregating platform facilitates the delivery of patient-reported outcome measures and collection of wearable data to researchers, while reducing patient burden compared to traditional patient-generated data collection and aggregation methodsHeterogeneity in patient willingness or comfort engaging with mobile products including smartphones and wearables, enrollment primarily at large academic centers, and the modest sample size are potential limitations to the external validity of the study.

Acute pain pathways: protocol for a prospective cohort study.

INTRODUCTION: Opioid analgesics are often used to treat moderate-to-severe acute non-cancer pain; however, there is little high-quality evidence to guide clinician prescribing. An essential element to developing evidence-based guidelines is a better understanding of pain management and pain control among individuals experiencing acute pain for various common diagnoses. METHODS AND ANALYSIS: This multicentre prospective observational study will recruit 1550 opioid-naïve participants with acute pain seen in diverse clinical settings including primary/urgent care, emergency departments and dental clinics. Participants will be followed for 6 months with the aid of a patient-centred health data aggregating platform that consolidates data from study questionnaires, electronic health record data on healthcare services received, prescription fill data from pharmacies, and activity and sleep data from a Fitbit activity tracker. Participants will be enrolled to represent diverse races and ethnicities and pain conditions, as well as geographical diversity. Data analysis will focus on assessing patients' patterns of pain and opioid analgesic use, along with other pain treatments; associations between patient and condition characteristics and patient-centred outcomes including resolution of pain, satisfaction with care and long-term use of opioid analgesics; and descriptive analyses of patient management of leftover opioids. ETHICS AND DISSEMINATION: This study has received approval from IRBs at each site. Results will be made available to participants, funders, the research community and the public. TRIAL REGISTRATION NUMBER: NCT04509115.

Comparison of two independent systematic reviews of trials of recombinant human bone morphogenetic protein-2 (rhBMP-2): the Yale Open Data Access Medtronic Project.

BACKGROUND: It is uncertain whether the replication of systematic reviews, particularly those with the same objectives and resources, would employ similar methods and/or arrive at identical findings. We compared the results and conclusions of two concurrent systematic reviews undertaken by two independent research teams provided with the same objectives, resources, and individual participant-level data. METHODS: Two centers in the USA and UK were each provided with participant-level data on 17 multi-site clinical trials of recombinant human bone morphogenetic protein-2 (rhBMP-2). The teams were blinded to each other's methods and findings until after publication. We conducted a retrospective structured comparison of the results of the two systematic reviews. The main outcome measures included (1) trial inclusion criteria; (2) statistical methods; (3) summary efficacy and risk estimates; and (4) conclusions. RESULTS: The two research teams' meta-analyses inclusion criteria were broadly similar but differed slightly in trial inclusion and research methodology. They obtained similar results in summary estimates of most clinical outcomes and adverse events. Center A incorporated all trials into summary estimates of efficacy and harms, while Center B concentrated on analyses stratified by surgical approach. Center A found a statistically significant, but small, benefit whereas Center B reported no advantage. In the analysis of harms, neither showed an increased cancer risk at 48 months, although Center B reported a significant increase at 24 months. Conclusions reflected these differences in summary estimates of benefit balanced with small but potentially important risk of harm. CONCLUSIONS: Two independent groups given the same research objectives, data, resources, funding, and time produced broad general agreement but differed in several areas. These differences, the importance of which is debatable, indicate the value of the availability of data to allow for more than a single approach and a single interpretation of the data. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42012002040 and CRD42012001907 .