Enhancing Patient Centricity of Real-World Data Research: An Exploratory Analysis Using the Patient Experience Mapping Toolbox.

OBJECTIVES: There is an increasing expectation that medical product development and assessment be guided by patient input captured through patient engagement. Recently published consensus guidelines describe how qualitative patient experience data (PED) can guide the design, conduct, and translation of real-world research that reflects patients' lived experience. The objective of this exploratory analysis is to examine how researchers could leverage PED captured through the Patient Experience Mapping Toolbox (PEMT) to guide real-world data (RWD) research designs. METHODS: This exploratory analysis included a thematic analysis of interview transcripts collected while pilot testing the PEMT followed by a qualitative analysis of the emerging themes aligned with stages listed in the patient-centered real-world evidence, Real-World Research Design Framework. RESULTS: PED collected using the PEMT include information about symptomology, interactions with the healthcare system, information-seeking behavior, misdiagnoses, lifestyle changes, treatments, side effects, and comorbidities. This information can be leveraged at key study design decisions, including (1) identifying study cohorts and subgroups, (2) identifying exposures, (3) informing covariates and potential confounders; and (4) refining study periods. Additionally, participants described where they seek information about treatments and diseases, which should inform dissemination strategies. CONCLUSIONS: We identified opportunities for PED collected using the PEMT to inform RWD study designs. The PED described in this exploratory analysis stem from pilot testing of the PEMT across a variety of conditions. In the next phase of development in this area, researchers should evaluate how data collected using the PEMT can be applied to RWD research for a specific disease.

Benzonatate Safety and Effectiveness: A Systematic Review of the Literature.

OBJECTIVE: To review the available literature regarding the treatment effects and efficacy of benzonatate needed to better inform patients, providers, and regulators evaluating its role in modern medical therapies. DATA SOURCES: Comprehensive literature searches were conducted in PubMed, Embase (Elsevier), Cochrane Library, and Scopus for original research articles evaluating the effectiveness, tolerability, and safety profile of benzonatate from January 1956 through August 2022. STUDY SELECTION AND DATA EXTRACTION: The identified studies were screened for relevance and then assessed for inclusion through a full-text review, data extraction, and quality assessment by multiple reviewers using the online software Covidence. DATA SYNTHESIS: The selection process resulted in 37 articles consisting of 21 cohort studies, 5 experimental studies, and 11 case studies and series. Initial clinical studies exploring potential therapeutic benefits collected data from very small populations and limited clinical settings. Safety is primarily assessed in terms of toxicity due to overdose or inappropriate use. Quality assessment raised concerns for high degrees of biases primarily related to the limited sample size, data collection, generalizability, and study design. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: This review reveals substantial limitations within existing evidence pertaining to the safety and clinical effectiveness of benzonatate and thus, a need for large observational studies or randomized trials to better characterize its role and value in modern medical practice. CONCLUSIONS: Rising safety concerns should bring closer scrutiny upon the prescription of benzonatate whose approval is founded upon evidence that would not stand up to current regulatory review.

Naloxone Prescribing Associated With Reduced Emergency Department Visits in the Military Health System.

PURPOSE: The aim was to determine the association between the receipt of naloxone and emergency department (ED) visits within 60 days after the receipt of an opioid. METHODS: A retrospective cohort of individuals 18 years of age or above, enrolled in TRICARE, and were dispensed an opioid at any time from January 1, 2019, through September 30, 2020 was identified within the United States Military Health System. Individuals receiving naloxone within 5 days of the opioid dispensing date were propensity score matched with individuals receiving opioids only. A logistic regression was used to estimate the odds of an ED visit in the 60-day follow-up period after the index opioid dispense event among those co-dispensed naloxone and those receiving opioids only. RESULTS: Of the 2,136,717 individuals who received an opioid prescription during the study period, 800,071 (10.1%) met study inclusion criteria. Overall, 5096 (0.24%) of individuals who received an opioid prescription were co-dispensed naloxone. Following propensity score matching, those who received naloxone had a significantly lower odds of ED utilization in the 60 days after receiving an opioid prescription (odds ratio: 0.74, 95% CI: 0.68-0.80, P<0.001). CONCLUSION: This study highlights the importance of expanding access to naloxone in order to reduce ED utilization. Future research is needed to examine additional outcomes related to naloxone receipt and develop programs that make naloxone prescribing a routine practice.

Association between opioid therapy trajectories and potential opioid-related adverse health events.

PURPOSE: We identified associations between membership in seven group-based trajectories based on supply of filled opioid prescriptions and potential opioid-related adverse health events over a 720-day window. METHODS: We identified two veteran cohorts with chronic non-cancer pain who initiated treatment with long-term opioid therapy between 2008 and 2015, excluding those with prior substance use disorder (n = 373 941) or non-SUD, opioid-related adverse outcome (n = 405 631) diagnoses. Outcomes of interest included opioid use disorder, non-opioid drug use disorder, and alcohol use disorder for the first cohort; or accidents resulting in wounds or injuries, self-inflicted injuries, opioid-related accidents and overdoses, alcohol and non-opioid drug-related accidents and overdoses, and violence-related injuries for the second cohort. Using a cross-sectional design, Veterans were followed until the specific outcome of interest was diagnosed, they died, the study ended, or they were lost to follow up. Accelerated failure time models were estimated for each outcome. RESULTS: Membership in persistent moderate days covered and persistent modest days covered trajectories was associated with decreased risk of opioid use disorder (Moderate: θ = 0.59, 95%CI:0.54, 0.64; Modest: θ = 0.54, 95%CI:0.50, 0.59) and opioid overdose (Moderate: θ = 0.67,95%CI: 0.57, 0.79; Modest: θ = 0.72, 95%CI:0.61, 0.85) versus higher-utilizing persistent users. Rapid discontinuation was associated with decreased risk of opioid use disorder (θ = 0.86, 95% CI:0.77, 0.95) and opioid overdose (θ = 0.54, 95%CI:0.41, 0.71), but increased risk of alcohol use disorder (θ = 1.07, 95%CI:1.00, 1.15) and other substance use disorders. Delayed discontinuation or delayed reduction was associated with increased risk for most opioid related adverse health events. CONCLUSION: Persistent use trajectories with low levels of opioid utilization were associated with lower risks of potential opioid-related adverse health events.

Development and Testing of a Chronic-Disease Patient Experience Mapping Toolbox.

BACKGROUND: Stakeholders increasingly expect research and care delivery to be guided by and to optimize patient experiences. However, standardized tools to engage patients to gather high-quality data about their experiences, priorities, and desired outcomes are not publicly available. The objective of this study was to develop and test a Toolbox with a disease-agnostic interview guide template and accompanying resources to assist researchers in engaging patients living with chronic disease in a dialogue about their experiences. METHODS: Guided by a multidisciplinary workgroup, a targeted literature review (PubMed) was conducted, followed by group discussions to identify/thematically organize patient experience concepts, development of a conceptual model, and drafting of an interview guide template and patient-facing visual. Materials were tested/refined via cognitive (n = 5) and pilot (n = 30) interviews conducted virtually with US patients diagnosed with chronic/potentially disabling conditions from December 2020 to April 2021. Patient-facing tools were reviewed by health literacy experts for applicability/accessibility. English-speaking adults who self-reported receiving a chronic condition diagnosis at least 6 months prior participated in a 60-90 min interview. RESULTS: Patient experience concepts were organized thematically under three domains: (1) life before a diagnosis, (2) experiences getting a diagnosis, and (3) experiences living with a diagnosis. A plain language consent sheet template, interview guide template, and patient experience conceptual model were developed and revised based on input from interviewees, interviewers, and the workgroup. CONCLUSIONS: A disease-agnostic patient-engagement Toolbox was developed and tested to capture patient experience data. These materials can be customized based on study objectives and leveraged by various stakeholders to identify opportunities to enhance the patient centricity of healthcare delivery and research.

A Quantitative Framework to Identify and Prioritize Opportunities in Biomedical Product Innovation: A Proof-of-Concept Study.

Importance: Prioritization and funding for health initiatives, including biomedical innovation, may not consistently target unmet public health needs. Objective: To (1) develop a quantitative, databased framework to identify and prioritize opportunities for biomedical product innovation investments based on a multicriteria decision-making model (MCDM) that includes comprehensive measures of public health burden and health care costs, and (2) pilot test the model. Design, Setting, and Participants: The Department of Health and Human Services (HHS) convened public and private experts to develop a model, select measures, and complete a longitudinal pilot study to identify and prioritize opportunities for investment in biomedical product innovations that have the greatest public health benefit. Cross-sectional and longitudinal data (2012-2019) for 13 pilot medical disorders were obtained from the Institute for Health Metrics Global Burden of Disease database (IHME GBD) and the National Center for Health Statistics (NCHS). Main Outcome Measures: The main outcome measure was an overall gap score reflecting high public health burden (composite measure of mortality, prevalence, years lived with disability, and health disparities), or high health care costs (composite measure of total, public, and out-of-pocket health spending) relative to low biomedical innovation. Sixteen innovation metrics were selected to reflect the pipeline of biomedical products from research and development to market approval. A higher score indicates a greater gap. Normalized composite scores were calculated for public health burden, cost, and innovation investment using the MCDM Technique for Order of Preference by Similarity to Ideal Solution method. Results: Among the 13 conditions tested in the pilot study, diabetes (0.61), osteoarthritis (0.46), and drug-use disorders (0.39) had the highest overall gap score reflecting high public health burden, or high health care costs relative to low biomedical innovation in these medical disorders. Chronic kidney disease (0.05), chronic obstructive pulmonary disease (0.09), and cirrhosis and other liver diseases (0.10) had the least amount of biomedical product innovation despite similar public health burden and health care cost scores. Conclusions: In this cross-sectional pilot study, we developed and implemented a data-driven, proof-of-concept model that can help identify, quantify, and prioritize opportunities for biomedical product innovation. Quantifying the relative alignment between biomedical product innovation, public health burden, and health care cost may help identify and prioritize investments that can have the greatest public health benefit.

Data sources and applied methods for paclitaxel safety signal discernment.

Background: Following the identification of a late mortality signal, the Food and Drug Administration (FDA) convened an advisory panel that concluded that additional clinical study data are needed to comprehensively evaluate the late mortality signal observed with the use of drug-coated balloons (DCB) and drug-eluting stent (DES). The objective of this review is to (1) identify and summarize the existing clinical and cohort studies assessing paclitaxel-coated DCBs and DESs, (2) describe and determine the quality of the available data sources for the evaluation of these devices, and (3) present methodologies that can be leveraged for proper signal discernment within available data sources. Methods: Studies and data sources were identified through comprehensive searches. original research studies, clinical trials, comparative studies, multicenter studies, and observational cohort studies written in the English language and published from January 2007 to November 2021, with a follow-up longer than 36 months, were included in the review. Data quality of available data sources identified was assessed in three groupings. Moreover, accepted data-driven methodologies that may help circumvent the limitations of the extracted studies and data sources were extracted and described. Results: There were 39 studies and data sources identified. This included 19 randomized clinical trials, nine single-arm studies, eight registries, three administrative claims, and electronic health records. Methodologies focusing on the use of existing premarket clinical data, the incorporation of all contributed patient time, the use of aggregated data, approaches for individual-level data, machine learning and artificial intelligence approaches, Bayesian approaches, and the combination of various datasets were summarized. Conclusion: Despite the multitude of available studies over the course of eleven years following the first clinical trial, the FDA-convened advisory panel found them insufficient for comprehensively assessing the late-mortality signal. High-quality data sources with the capabilities of employing advanced statistical methodologies are needed to detect potential safety signals in a timely manner and allow regulatory bodies to act quickly when a safety signal is detected.

Building the foundation for a modern patient-partnered infrastructure to study temporomandibular disorders.

Background: Conflicting reports from varying stakeholders related to prognosis and outcomes following placement of temporomandibular joint (TMJ) implants gave rise to the development of the TMJ Patient-Led RoundTable initiative. Following an assessment of the current availability of data, the RoundTable concluded that a strategically Coordinated Registry Network (CRN) is needed to collect and generate accessible data on temporomandibular disorder (TMD) and its care. The aim of this study was therefore to advance the clinical understanding, usage, and adoption of a core minimum dataset for TMD patients as the first foundational step toward building the CRN. Methods: Candidate data elements were extracted from existing data sources and included in a Delphi survey administered to 92 participants. Data elements receiving less than 75% consensus were dropped. A purposive multi-stakeholder sub-group triangulated the items across patient and clinician-based experience to remove redundancies or duplicate items and reduce the response burden for both patients and clinicians. To reliably collect the identified data elements, the identified core minimum data elements were defined in the context of technical implementation within High-performance Integrated Virtual Environment (HIVE) web-application framework. HIVE was integrated with CHIOS™, an innovative permissioned blockchain platform, to strengthen the provenance of data captured in the registry and drive metadata to record all registry transaction and create a robust consent network. Results: A total of 59 multi-stakeholder participants responded to the Delphi survey. The completion of the Delphi surveys followed by the application of the required group consensus threshold resulted in the selection of 397 data elements (254 for patient-generated data elements and 143 for clinician generated data elements). The infrastructure development and integration of HIVE and CHIOS™ was completed showing the maintenance of all data transaction information in blockchain, flexible recording of patient consent, data cataloging, and consent validation through smart contracts. Conclusion: The identified data elements and development of the technological platform establishes a data infrastructure that facilitates the standardization and harmonization of data as well as perform high performance analytics needed to fully leverage the captured patient-generated data, clinical evidence, and other healthcare ecosystem data within the TMJ/TMD-CRN.

Creation of objective performance criteria among medical devices.

Objectives: Objective performance criteria (OPC) may serve as a tool to expedite the approval process and continue active surveillance of class III medical devices. Thus far, published guidance on the creation of OPC has been clinical area-specific. This study aimed to capture reflections from key stakeholders on the creation of OPC that may serve as a precursor for a formalized conceptual framework within the USA. Design: Reflections from key stakeholders and guidance from an advisory committee were captured to gain an understanding of the elements that are crucial to the generation of OPC. Setting: A non-probability sampling method using the purposive sampling strategy was employed to identify relevant stakeholders for engagement in semi-structured, open-ended, concept elicitation discussions. Participants: Stakeholders involved in the generation of OPC. Main outcome measures: Elements and themes regarding the priorities of, experiences with, roles within and perceived challenges associated with OPC creation captured through a phenomenological approach. Results: A total of 27 participants were engaged to represent the following contributors: representatives of registries, health systems, health technology assessment bodies, clinicians, device application reviewers, payers, patients, patient representatives, patient caregivers, device manufacturers, data coordinators, data analysts and data informaticians. Consensus was achieved on the five core elements: (1) identification of medical devices, (2) engagement of key stakeholders, (3) selection of data source, (4) performance of appropriate statistical analyses and (5) reporting of findings. The engagement of key stakeholders (38%) was cited most frequently as the most important core element. Access to meaningful and high-quality data sources (47%) was the most frequently mentioned challenge. Conclusions: The reflections from the participants identified five elements to be considered when generating an OPC within class III medical devices and may provide the needed foundation for the development of official guidance on OPC generation.

Development of a core minimum data set to advance real-world evidence generation for uterine fibroids treatment technologies.

Objectives: The accumulation of data through a prospective, multicenter coordinated registry network (CRN) is a robust and cost-effective way to gather real-world evidence on the performance of uterine fibroids treatment technologies for device-based and intervention-based studies. To develop the CRN, a group of uterine fibroids experts, consisting of representatives from professional societies, the US Food and Drug Administration, academia, industry, and the patient community, was convened to discuss the role and feasibility of the CRN and to identify the core data elements needed to assess uterine fibroid treatment technologies. Design: A Delphi method approach was employed to achieve consensus on a core minimum data set for the CRN. A series of surveys were sent to the panel and answered by each expert anonymously and individually. Results from the surveys were collected, collated, and analyzed by a study design team from Weill Cornell Medicine. Questions for the next round were based on the analysis process and discussed with group members via a conference call. This process was repeated twice over a 3-month time period until consensus was achieved. Results: Twenty-nine experts participated in the Delphi surveys, which began with an initial list of 200 data elements. The working group reached final consensus on 97 data elements capturing patient medical history, imaging data, procedure-related data, post-procedure data, and long-term follow-up data. Conclusions: The CRN successfully convened an expert panel on uterine fibroids treatment technologies and used the Delphi method to produce a consensus-based core set of data elements. These identified data elements include important outcomes related to efficacy and safety and thus, influence patient, provider, and regulatory decision-making about treatments for uterine fibroids. Finally, the core data elements provide the foundation of the infrastructure needed for the CRN that will allow for the comparative study of uterine fibroid treatment devices and technologies.

Building Blocks for the Long-acting and Permanent Contraceptives Coordinated Registry Network.

Objectives: A multistakeholder expert group under the Women's Health Technology Coordinated Registry Network (WHT-CRN) was organized to develop the foundation for national infrastructure capturing the performance of long-acting and permanent contraceptives. The group, consisting of representatives from professional societies, the US Food and Drug Administration, academia, industry and the patient community, was assembled to discuss the role and feasibility of the CRN and to identify the core data elements needed to assess contraceptive medical product technologies. Design: We applied a Delphi survey method approach to achieve consensus on a core minimum data set for the future CRN. A series of surveys were sent to the panel and answered by each expert anonymously and individually. Results from the surveys were collected, collated and analyzed by a study design team from Weill Cornell Medicine. After the first survey, questions for subsequent surveys were based on the analysis process and conference call discussions with group members. This process was repeated two times over a 6-month time period until consensus was achieved. Results: Twenty-three experts participated in the Delphi process. Participation rates in the first and second round of the Delphi survey were 83% and 100%, respectively. The working group reached final consensus on 121 core data elements capturing reproductive/gynecological history, surgical history, general medical history, encounter information, long-acting/permanent contraceptive index procedures and follow-up, procedures performed in conjunction with the index procedure, product removal, medications, complications related to the long-acting and/or permanent contraceptive procedure, pregnancy and evaluation of safety and effectiveness outcomes. Conclusions: The WHT-CRN expert group produced a consensus-based core set of data elements that allow the study of current and future contraceptives. These data elements influence patient and provider decisions about treatments and include important outcomes related to safety and effectiveness of these medical devices, which may benefit other women's health stakeholders.