FDA Public Workshop Summary-Addressing Challenges in Inhaled Antifungal Drug Development.

Allergic bronchopulmonary aspergillosis and invasive fungal diseases represent distinct infectious entities that cause significant morbidity and mortality. Currently, administered inhaled antifungal therapies are unapproved, have suboptimal efficacy, and are associated with considerable adverse reactions. The emergence of resistant pathogens is also a growing concern. Inhaled antifungal development programs are challenged by inadequate nonclinical infection models, highly heterogenous patient populations, low prevalence rates of fungal diseases, difficulties defining clinical trial enrollment criteria, and lack of robust clinical trial endpoints. On September 25, 2020, the US Food and Drug Administration (FDA) convened a workshop with experts in pulmonary medicine and infectious diseases from academia, industry, and other governmental agencies. Key discussion topics included regulatory incentives to facilitate development of inhaled antifungal drugs and combination inhalational devices, limitations of existing nonclinical models and clinical trial designs, patient perspectives, and industry insights.

Social media for early characterization of pandemic symptoms: A qualitative analysis of patient-reported COVID-19 experiences.

BACKGROUND: Patients use social media forums to discuss their medical history and healthcare experiences, providing early insight into real-world patient experiences. We analyzed COVID-19 patient experiences from Reddit social media posts. METHODS: We extracted Reddit Application Programming Interface data for the subreddit/COVID-19 positive from March to August 2020 and selected users tagged as "Tested Positive" or "Tested Positive- Me" flair and who posted at least thirty times in any calendar month, excluding users who explicitly stated location outside of the U.S. For tested-positive patients (users), we created and reviewed individual case profiles summarizing their COVID-19 symptoms, testing, and medications or treatments. Data were imported to Nvivo qualitative analysis software and qualitative coding was conducted. FINDING: There were 31 759 posts and comments from 720 users in March to May 2020 (Q1) and 40 446 posts and comments from 1649 users from June to August 2020 (Q2). Final count of "Tested Positive" was 1296 users (280 in Q1 and 1016 in Q2). Across both quarters, frequently reported symptoms included sore throat, headaches, fevers, or chills. Loss of sense of smell or taste were reported by users in early March, prior to the inclusion of this symptom to the CDC list in April and GI-related symptoms and fatigue were reported in the March to May data, before they were added as a COVID-19 associated symptom in July 2020. Users also reported in-depth descriptions of their symptoms, motivations for testing, and long-term impacts such as post-viral fatigue. INTERPRETATION: Social media data can potentially serve as an early surveillance data source in a pandemic and offer preliminary insights into patient disease experiences.

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.

Considerations in the Assessment of Clinical Benefit with a Focus on Pain: a Regulatory Perspective.

In the USA, the regulatory standard for demonstration of efficacy of a drug is evidence of clinical benefit from adequate and well-controlled clinical trials. Understanding the natural history of disease and how treatment is expected to alter its course, and gathering input from relevant stakeholders, such as patients, caregivers, and clinicians, is essential to understand the best way to measure clinical benefit in a clinical trial. Though pain intensity has been the primary outcome measure in clinical trials for pain, an array of measures assessing clinical outcomes from multiple perspectives can allow for more comprehensive interpretation of how a treatment affects patients' lives. Careful consideration should be given to how pain affects the feeling and functioning of each distinct patient population and which outcome assessment, or combination of outcome assessments, may be necessary to provide a more comprehensive view of the patient experience. The early stages of medical product development are an important opportunity to engage with regulatory agencies to discuss potential approaches to clinical trial design and outcome measurement strategies.

Characteristics Associated With U.S. Outpatient Opioid Analgesic Prescribing and Gabapentinoid Co-Prescribing.

INTRODUCTION: A considerable burden of prescription and illicit opioid-related mortality and morbidity in the U.S. is attributable to potentially unnecessary or excessive opioid prescribing, and co-prescribing gabapentinoids may increase risk of harm. Data are needed regarding physician and patient characteristics associated with opioid analgesic and opioid analgesic-gabapentinoid co-prescriptions to elucidate targets for reducing preventable harm. METHODS: Multiple logistic regression was utilized to examine patient and physician predictors of opioid analgesic prescriptions and opioid analgesic-gabapentinoid co-prescriptions in adult noncancer patients using the National Ambulatory Medical Care Survey 2015 public use data set. Potential predictors were selected based on literature review, clinical relevance, and random forest machine learning algorithms. RESULTS: Among the 11.8% (95% CI=9.8%, 13.9%) of medical encounters with an opioid prescription, 16.2% (95% CI=12.6%, 19.8%) had a gabapentinoid co-prescription. Among all gabapentinoid encounters, 40.7% (95% CI=32.6%, 48.7%) had an opioid co-prescription. Predictors of opioid prescription included arthritis (OR=1.87, 95% CI=1.30, 2.69). Predictors of new opioid prescription included physician status as an independent contractor (OR=3.67, 95% CI=1.38, 9.81) or part owner of the practice (OR=3.34, 95% CI=1.74, 6.42). Predictors of opioid-gabapentinoid co-prescription included patient age (peaking at age 55-64 years; OR=35.67, 95% CI=4.32, 294.43). CONCLUSIONS: Predictors of opioid analgesic prescriptions with and without gabapentinoid co-prescriptions were identified. These predictors can help inform and reinforce (e.g., educational) interventions seeking to reduce preventable harm, help identify populations for elucidating opioid-gabapentinoid risk-benefit profiles, and provide a baseline for evaluating subsequent public health measures.

Assessment of public and patient online comments in social media and food and drug administration archival data.

OBJECTIVES: To refine a method of collecting the data from various patient generated data sources to explore themes with high repeatability. FDA will acquire new insight into understanding the perspectives of patients and caregivers through analyses of multiple sources. DESIGN: Qualitative analysis of FDA archival data and social media data. SETTING: Two pilot studies assessing methodologies on differing unstructured data sources. Study 1: Opioid Use Disorder (OUD), analyzing OUD public docket comments and social media data. STUDY 2: Pulmonary Arterial Hypertension (PAH), utilizing FDA's PAH PFDD meeting transcripts and 1813 Online User Generated Content (UGC) posts. RESULTS: Through triangulation of data, FDA identified data overlaps (thus increasing confidence of data) and located information found only in certain sources. CONCLUSIONS: and Relevance: For research to be patient centric, leveraging technological advances and multiple patient experience data sources captures the patient perspective beyond clinical delivery and provides additional information and aids in understanding the picture of medical product functioning beyond controlled randomized clinical trials.