Food And Drug Administration Recommendations Research Articles

Scientific and Regulatory Policy Committee Points to Consider: Review of the United States Food and Drug Administration (FDA) Guidance on Pathology Peer Review in Nonclinical Toxicology Studies.

In December 2021, the United States Food and Drug Administration (FDA) issued the final guidance for industry titled Pathology Peer Review in Nonclinical Toxicology Studies: Questions and Answers. The stated purpose of the FDA guidance is to provide information to sponsors, applicants, and nonclinical laboratory personnel regarding the management and conduct of histopathology peer review as part of nonclinical toxicology studies conducted in compliance with good laboratory practice (GLP) regulations. On behalf of and in collaboration with global societies of toxicologic pathology and the Society of Quality Assurance, the Scientific and Regulatory Policy Committee (SRPC) of the Society of Toxicologic Pathology (STP) initiated a review of this FDA guidance. The STP has previously published multiple papers related to the scientific conduct of a pathology peer review of nonclinical toxicology studies and appropriate documentation practices. The objectives of this review are to provide an in-depth analysis and summary interpretation of the FDA recommendations and share considerations for the conduct of pathology peer review in nonclinical toxicology studies that claim compliance to GLP regulations. In general, this working group is in agreement with the recommendations from the FDA guidance that has added clear expectations for pathology peer review preparation, conduct, and documentation.

Abstract 12908: Non-Fatal Trial Endpoints of Drug Interventions in Heart Failure

Introduction: The Food and Drug Administration (FDA) provides guidance on the use of endpoints for drug approvals in heart failure (HF). Hypothesis: The aim of this study was to systematically review whether clinical studies in HF report the FDA recommendations for endpoints. Methods: All studies targeting HF available on the clinical trials platform from the National Library of Medicine were analyzed. The FDA recommends a decrease in mortality as the primary efficacy endpoint and an increase in survival as the safety endpoint. Others include single or composite scores of hospitalizations, biomarkers, or symptoms and/or physical function. Results: Trials (n=4,978) were narrowed down to 1,299 (26%) studies with an active, but not recruiting, enrolling by invitations, not yet recruiting, and recruiting statuses. Only 132 (3%) studies using intervention with drugs reported endpoints. Up to 7,200 participants were randomly (n=95, 72%) assigned to parallel designs (n=81, 61%) followed by single group (n=19, 14%) or crossover designs (n=18, 14%) with open label (n=48, 36%) or quadruple masking methods (n=29, 22%). Interventions tested sodium-glucose co-transporter 2 (n=21, 16%) and angiotensin receptor-neprilysin inhibitors (n=13, 10%). Dapagliflozin (n=8, 8%), Sacubitril and Valsartan (n=6, 6%) followed by Levosimendan, Metformin, or Warfarin (n=3, 3%) were compared to placebo (n=51, 53%). Equivalence trials (n=35, 27%) analyzed Sacubitril and Valsartan (n=5, 14%), Dapagliflozin, Beta-hydroxybutyrate Ester, or Sacubitril and Valsartan with Para-aminohippurate, Lohexol, and Aprepitant (n=2, 6%). Most studies (n=55, 42%) assessed endpoints related to symptoms and/or physical function. Other endpoints included cardiac function (n=24, 18%) and biomarkers (n=19, 14%) followed by mortality and survival (n=18, 14%) or hospitalization (n=5, 4%). Conclusions: Most studies assessed symptoms, physical function, cardiac function, or biomarkers for primary endpoints. They have included non-fatal endpoints such as patient-reported outcomes or objective indicators likely due to the increasing number of patients with worsening heart failure in outpatient settings.

Black-Box Warnings of Antiseizure Medications: What is Inside the Box?

Antiseizure medications can cause serious adverse reactions and have deleterious drug interactions that often complicate the clinical management of patients. When the US Food and Drug Administration (FDA) wants to alert healthcare providers and patients about the risk of potentially serious or fatal drug reactions, the FDA requires the manufacturers of these medications to format these warnings within a "black-box" border, and prominently display this box on the first section of the package insert; such warnings are called "black-box warnings (BBWs)". The BBW is a way for the FDA to urge physicians to evaluate patients more rigorously and carefully weigh the risks and benefits, before prescribing medication that has the potential to cause serious adverse reactions, and toformulate a plan for close monitoring during therapy. The FDA BBW provides the extra layer of safety but many healthcare providers fail to comply with these warnings. Currently, there are 26 FDA-approved antiseizure medications in the US market, 38% of which have received BBWs, and most of the antiseizure medications with BBWs are older-generation drugs. Some antiseizure medications have multiple BBWs; for example, valproic acid has three BBWs including hepatotoxicity, fetal risk, and pancreatitis, carbamazepine has BBWs of serious skin and hematological reactions, and felbamate also has two BBWs including hepatic failure and aplastic anemia. The purpose of this review is to provide insight into each BBW received by antiseizure medications and discuss the FDA recommendations for evaluating the drug benefit/risk, and formonitoring parameters before the initiation ofand during treatment.

The impact of voluntary folate fortification of corn masa flour on US pregnancies complicated by neural tube defects

IntroductionIn 1996, the US Food and Drug Administration (FDA) mandated folic acid fortification for all enriched cereal grains. This resulted in a reduction of neural tube defect (NTD)–affected pregnancies. However, Hispanic women continued to be twice as likely to give birth to a child affected by NTD compared to non-Hispanic White women. Some hypotheses explaining this difference focus on cultural variation in dietary intake of cereal grains. In 2016, the FDA approved voluntary folic acid fortification for corn masa flour products to focus on the Hispanic diet staple. This study investigates rates of NTDs in predominantly Hispanic-populated zip codes before and after the voluntary fortification of corn masa flour with folic acid.MethodsNormal pregnancies and those complicated by NTDs between 1/1/2016 and 9/30/2020 were identified using ICD-9 and ICD-10 codes in an all-payor claims database. The post-fortification period began 12 months after the fortification recommendation. The US Census data was used to stratify pregnancies in predominantly Hispanic zip codes (≥ 75% of households) vs. non-Hispanic zip codes. The causal impact of the FDA’s recommendation was assessed by means of a Bayesian structural time series model.ResultsA total of 2,584,366 pregnancies were identified among females aged 15–50 years. Of these, 365,983 took place in predominantly Hispanic zip codes. Mean quarterly NTDs per 100,000 pregnancies did not significantly differ between predominantly Hispanic zip codes and predominantly non-Hispanic zip codes pre-FDA recommendation (184.5 vs. 175.6; p = 0.427), nor post-recommendation (188.2 vs. 185.9; p = 0.713). Rates of NTDs predicted to occur if no FDA recommendation had been made were compared to the actual rate post-recommendation: no significant difference was observed in predominantly Hispanic zip codes (p = 0.245) or overall (p = 0.116).ConclusionsRates of neural tube defects were not significantly reduced in predominantly Hispanic zip codes following the 2016 FDA approval of voluntary folic acid fortification of corn masa flour. Further research and implementation of comprehensive approaches to advocacy, policy, and public health are necessary to decrease preventable congenital disease rates. Mandatory rather than voluntary fortification of corn masa flour products may achieve more substantial prevention of neural tube defects in at-risk US populations.

Development of an in-vitro model based on patient vessel geometry for simulated use testing in neurointerventional surgery.

Neurointerventionalists use in-vitro vascular models to train for worst-case scenarios and test new devices in a simulated use environment to predict clinical performance. According to the Food and Drug Administration (FDA), any neurovascular navigation device should be able to successfully navigate two 360-degree turns and two 180-degree turns at the distal portion of the anatomical model. Here, we present a device benchmarking vascular model that complies with FDA recommendations. Our vascular model was assembled from quantitative characterization of 49 patients who underwent CT angiography either for acute ischemic stroke caused by large vessel occlusion or for aneurysm treatment. Following complete characterization of these data, the vascular segments were 3D reconstructed from CT angiograms of 6 selected patients that presented with challenging anatomy. The curvature and total rotational angle were calculated for each segment and the anatomical parts that complied with FDA recommendations were fused together into a single in-vitro model. The model was constructed containing two common carotid branches arising from a type two aortic arch and the dimensions of the overall model exceeded the recommendations of the FDA. Two experienced neurointerventionalists tested the model for navigation difficulty using several devices on an in-vitro perfusion system and concluded that the model provided a realistic, challenging scenario. This model provides a first prototype designed according to FDA recommendations of cumulative angle while also integrating an aggregation of actual patient-specific anatomy. The availability of this clinically relevant benchmark model presents a potential standardized approach for neurovascular device testing.

Updated Trends in Inferior Vena Cava Filter Use by Indication in the United States After Food and Drug Administration Safety Warnings: A Decade Analysis From 2010 to 2019.

Overall inferior vena cava filter (IVCF) utilization has decreased in the United States since the 2010 US Food and Drug Administration (FDA) safety communication. The FDA renewed this safety warning in 2014 with additional mandates on reporting IVCF-related adverse events. We evaluated the impact of the FDA recommendations on IVCF placements for different indications from 2010 to 2019 and further assessed utilization trends by region and hospital teaching status. Inferior vena cava filter placements between 2010 and 2019 were identified in the Nationwide Inpatient Sample database using the associated International Classification of Diseases, Ninth Revision, Clinical Modification, and Tenth Revision codes. Inferior vena cava filter placements were categorized by indication for venous thromboembolism (VTE) "treatment" in patients with VTE diagnosis and contraindication to anticoagulation and "prophylaxis" in patients without VTE. Generalized linear regression was used to analyze utilization trends. A total of 823 717 IVCFs were placed over the study period, of which 644 663 (78.3%) were for VTE treatment and 179 054 (21.7%) were for prophylaxis indications. The median age for both categories of patients was 68 years. The total number of IVCFs placed for all indications decreased from 129 616 in 2010 to 58 465 in 2019, with an aggregate decline rate of -8.4%. The decline rate was higher between 2014 and 2019 than between 2010 and 2014 (-11.6% vs -7.2%). From 2010 to 2019, IVCF placement for VTE treatment and prophylaxis trended downward at rates of -7.9% and -10.2%, respectively. Urban nonteaching hospitals saw the highest decline for both VTE treatment (-17.2%) and prophylactic indications (-18.0%). Hospitals located in the Northeast region had the highest decline rates for VTE treatment (-10.3%) and prophylactic indications (-12.5%). The higher decline rate in IVCF placements between 2014 and 2019 compared with 2010 and 2014 suggests an additional impact of the renewed 2014 FDA safety indications on national IVCF utilization. Variations in IVCF use for VTE treatment and prophylactic indications existed across hospital teaching types, locations, and regions. Inferior vena cava filters (IVCF) are associated with medical complications. The 2010 and 2014 FDA safety warnings appeared to have synergistically contributed to a significant decline in IVCF utilization rates from 2010 - 2019 in the US. IVC filter placements in patients without venous thromboembolism (VTE) declined at a higher rate than VTE. However, IVCF utilization varied across hospitals and geographical locations, likely due to the absence of universally accepted clinical guidelines on IVCF indications and use. Harmonization of IVCF placement guidelines is needed to standardize clinical practice, thereby reducing the observed regional and hospital variations and potential IVC filter overutilization.

Online but unlawful sales of unapproved and misbranded prescription drugs: Internet pharmacy compliance with Food and Drug Administration warning letters

AbstractConsumers increasingly use online pharmacies. However, illicit online pharmacies endanger consumer welfare with unapproved and counterfeit drugs. By linking Food and Drug Administration (FDA) warning letter content with observations of the 1108 websites cited in those letters, we identify factors associated with FDA‐requested compliance and active/inactive website status. One in five online pharmacies failed to comply with FDA recommendations. Findings support the cost/benefit, social norm, and instrumental theories of compliance. Compliance declines with cost (e.g., when the FDA requests changes to more drug categories). Organized crime's social norms encourage law breaking; thus, illicit pharmacies comply less than other online pharmacies. Instrumental theory suggests perceived severity and certainty of penalties influences compliance. In support, when political will and attention focused on the opioid crisis, the FDA cited primarily opioid‐related violations and these opioid‐related letters increased compliance and website closures. Finally, we recommend improved consumer protection efforts to address internet pharmaceutical distribution challenges.

1754. Implementation of a targeted antimicrobial stewardship clinical decision support system on outpatient fluoroquinolone prescribing

Abstract Background Fluoroquinolones are broad spectrum antibiotics with several Food and Drug Administration (FDA)-issued black box warnings. Due to these risks, the FDA recommends reserving fluoroquinolones for situations with no alternatives. Beginning in 2020, the Joint Commission required outpatient antimicrobial stewardship activities due to overprescribing and growing resistance to antimicrobials. The role of this study was to implement a clinical decision support system (CDSS) targeting inappropriate outpatient fluoroquinolone prescribing. Methods This was a single center, quasi-experimental study evaluating patients prescribed oral fluoroquinolones in an outpatient ambulatory care setting between December 1, 2020-February 28, 2021 and December 1, 2021-February 28, 2022. Patients included in this study were divided into Pre-CDSS and Post-CDSS groups if they received oral antibiotics for pre-determined indications (see table 2 for the list of indications). The primary outcome was overall reduction in outpatient fluoroquinolone prescribing. Secondary objectives were reduction in outpatient fluoroquinolone prescribing by indication, orders by provider type, appropriate fluoroquinolone dosing per renal function and incidence of an emergency department (ED) visit or hospitalization within 90 days consistent with a fluoroquinolone adverse drug reaction. Results A total of 2,447 (1,105 in Pre-CDSS vs. 1,342 in Post-CDSS) were included for analysis. Fluoroquinolone prescribing significantly decreased in Post-CDSS group compared to Pre-CDSS group (4.9% vs. 3.4%; p = 0.03). There was a significant reduction in fluoroquinolone prescribing in abscess (8.5% vs. 4.9%; p = 0.003), dental abscess (4.4% vs. 0%; p < 0.00001), sinusitis (2.4% vs. 0.2%; p < 0.00001) and soft skin tissue infections (5.3% vs. 0.8%; p < 0.00001). In the fluoroquinolone subgroups, prescribing per provider type and appropriate dosing per renal function were similar, and there were no adverse events leading to an ED visit or hospitalization within 90 days. Conclusion Implementation of a CDSS resulted in a reduction of overall and targeted indication inappropriate fluoroquinolone prescribing. Disclosures Teri Fanizza, Pharm.D., BCPS, BCIDP, Merck & co inc: Stocks/Bonds|Pfizer Inc: Stocks/Bonds.

An Unusual Cause of Acidosis in a Man With Clostridium difficile Colitis

An Unusual Cause of Acidosis in a Man With Clostridium difficile Colitis

Patient-Reported Outcome Measures in Cardiovascular Disease: An Evidence Map of the Psychometric Properties of Health Status Instruments.

Patient-reported outcomes (PROs) are important measures of treatment effect and can be used to inform the approval of cardiovascular drugs and devices by the U.S. Food and Drug Administration (FDA). To catalogue the health status patient-reported outcome measures (PROMs) validated in cardiovascular diseases (CVDs), describe their psychometric properties, and assess adherence with both FDA recommendations and the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) framework. MEDLINE, EMBASE, CINAHL, and Allied and Complementary Medicine Database from inception to August 2022. Studies that developed and/or validated health status PROMs in CVD populations. Two study authors extracted data on CVD type, PROM psychometric properties, and adherence to FDA recommendations. The risk of bias informing the development or validation of PROMs was assessed using the COSMIN framework. Fifty health status PROMs (described in 83 studies) were identified, of which 45 were disease specific and 5 were generic. Eleven (22%) of the 50 PROMs validated in CVDs had minimally important differences (MIDs) established, and 8 (16%) reported on the validation of all psychometric properties recommended by the FDA. By COSMIN standards, only 2 PROMs (4%) had all of their psychometric properties rated as sufficient in quality, and 32 PROMs (64%) had less than 50% of psychometric properties rated as sufficient. The quality of reporting varied across included studies. Of 50 PROMs validated in CVDs, only a small minority reported on the validation of all FDA-recommended psychometric properties, had psychometric properties rated as sufficient by COSMIN, or had MIDs established. Given the use of PROMs to guide FDA approvals of drugs and devices in CVDs, there is a need for better adherence to quality standards in PROM validation. None.

Pediatric Practitioner Knowledge of Arsenic in Baby Food.

Rice, one of the first solid foods introduced to infants, is 10 times more absorbent of inorganic arsenic than any other grain. An evaluation has not been performed about practitioner knowledge of arsenic content in infant foods. The purpose of this survey was to determine pediatric practitioners' knowledge of current US Food and Drug Administration (FDA) recommendations to limit exposure to arsenic-containing foods in infants. This was a convenience sample of pediatric practitioners conducted as an online survey. The survey contained 19 questions related to knowledge of arsenic-containing foods, FDA recommendations, practitioner recommendations on feeding infants, and demographic information. Participants were recruited using organization list servs. Participants were reminded to complete the survey 2 months after the initial email. An infographic on arsenic was provided at the end of the survey. One hundred thirty-seven individuals completed the survey. The majority of respondents were physicians or pharmacists and have been in practice less than 6 years. Nine percent of respondents (11/123) stated the FDA arsenic limit of 100 ppb. Sixteen percent (20/123) identified white rice as having a lower inorganic arsenic content than brown rice and 27% (36/132) identified that there is no difference in inorganic arsenic content between organic infant rice cereal and conventional infant rice cereal. The vast majority of participants were not aware of the FDA's proposed limit on arsenic consumption or the concern of heavy metals in baby foods. More education is needed to increase knowledge regarding arsenic in baby foods.

Vitamin C and its therapeutic potential in the management of COVID19.

COVID19 has emerged as one of the worst pandemics in the history of mankind. Several vaccines have been approved by different government agencies worldwide, but data on their efficacy and safety are limited, and distribution remains a massive challenge. As per WHO, personal immunity is vital for protection against COVID19. Earlier, Vitamin C-mediated pathways have been shown to play critical role in boosting immunity attributed to its antioxidant properties. Recently, the involvement of such pathways in protection against COVID19 has been suggested. The controlled doses of Vitamin C administered through intravenous (IV) injections are being studied for determining its role in the prognosis of COVID19. In this article, we have discussed the potential role of Vitamin C in the management in COVID19 patients and presented recent clinical trials data. Additionally, we have elaborated the possibility of administering Vitamin C through inhalers in order to achieve local high concentration and the challenges of such approach.

Development and content validation of patient-reported outcomes tools for ulcerative colitis and Crohn’s disease in adults with moderate-to-severe disease

BackgroundUlcerative colitis (UC) and Crohn’s disease (CD) are associated with a range of symptoms that adversely affect health-related quality of life. This research aimed to develop and validate two patient-reported outcome (PRO) tools to assess signs and symptoms in patients with moderate-to-severe UC or CD.MethodsPRO-UC and PRO-CD Diaries were developed in accordance with US Food and Drug Administration (FDA) recommendations. Data were collected from concept elicitation interviews (in which patients described their symptoms and experience of the disease) and further refined through cognitive interviews (in which patients assessed the relevance and clarity of questions in the tools).ResultsInterviews were conducted with 12 patients for each indication. Five symptoms (urgent bowel movements, abdominal pain, frequent bowel movements, bloody stools, diarrhea/watery stools) were reported by 83–100% of participants with UC and were included in the final 6-item PRO-UC Diary: stool frequency, rectal bleeding (2 items), diarrhea, rectal urgency, and abdominal pain. For CD, seven symptoms (abdominal pain, diarrhea/loose stools, urgent bowel movements, fatigue/tiredness/weakness, frequent bowel movements, bloody stools, nausea) were reported by 50–100% of participants. These, together with vomiting and incontinence (reported by 42% and 33% of participants, respectively), were included in the final 10-item PRO-CD Diary, covering abdominal pain (2 items), stool frequency, liquid/very soft stool frequency, rectal bleeding, rectal urgency, nausea, vomiting, bowel incontinence, and general well-being. Symptoms were consistently cited across both indications to have an impact on quality of life, with frequent complaints being the need to always be near a toilet and inability to leave home, as well as general pain, discomfort, and nausea. For both tools, questions were accurately interpreted, with at least 67% of participants in both indications stating that items were easy to answer/relevant to their condition and symptoms were easy to recall over the last 24 h.ConclusionsBoth the PRO-UC and PRO-CD Diaries were developed and validated in accordance with FDA recommendations, providing two new tools for use in clinical trials to assess response to treatment in patients with UC or CD. Psychometric analyses are warranted to fully evaluate their properties and value for use in clinical trials.

Real-world data: Assessing electronic health records and medical claims data to support regulatory decision-making for drug and biological products.

Real-world data: Assessing electronic health records and medical claims data to support regulatory decision-making for drug and biological products.

Multicenter Clinical Evaluation of ETEST Plazomicin (PLZ) for Susceptibility Testing of Enterobacterales.

ABSTRACTPlazomicin (PLZ), brand name ZEMDRI (Cipla Therapeutics), is a novel aminoglycoside antibiotic approved by the U.S. Food and Drug Administration (FDA) for treatment of complicated urinary tract infections including pyelonephritis. ETEST® is a gradient diffusion method that represents an alternative to the more laborious broth micro-dilution (BMD) method for performing antimicrobial susceptibility testing (AST). A multi-center evaluation of the performance of the new ETEST PLZ (bioMérieux) was conducted in comparison with BMD following FDA and International Standards Organization (ISO) recommendations using FDA-defined breakpoints. Clinical isolates of Enterobacterales (n = 598) were included. Fifty-three isolates were resistant to PLZ according to BMD. Overall, the ETEST PLZ demonstrated 99.0% essential agreement (EA), 92.8% category agreement (CA), 1.9% very major errors (VME), 0% major errors (ME), and 7.0% minor errors (mE) with both clinical and challenge isolates of Enterobacterales. The VME was found for a single Serratia marcescens strain. Individual species demonstrated EA rates ≥ 90%. In conclusion, we report that ETEST PLZ represents an accurate tool for performing PLZ AST of Enterobacterales.

Mycobacterium chimaera infections among cardiothoracic surgery patients associated with heater-cooler devices-Kansas and California, 2019.

In 2015, an international outbreak of Mycobacterium chimaera infections among patients undergoing cardiothoracic surgeries was associated with exposure to contaminated LivaNova 3T heater-cooler devices (HCDs). From June 2017 to October 2020, the Centers for Disease Control and Prevention was notified of 18 patients with M. chimaera infections who had undergone cardiothoracic surgeries at 2 hospitals in Kansas (14 patients) and California (4 patients); 17 had exposure to 3T HCDs. Whole-genome sequencing of the clinical and environmental isolates matched the global outbreak strain identified in 2015. Investigations were conducted at each hospital to determine the cause of ongoing infections. Investigative methods included query of microbiologic records to identify additional cases, medical chart review, observations of operating room setup, HCD use and maintenance practices, and collection of HCD and environmental samples. Onsite observations identified deviations in the positioning and maintenance of the 3T HCDs from the US Food and Drug Administration (FDA) recommendations and the manufacturer's updated cleaning and disinfection protocols. Additionally, most 3T HCDs had not undergone the recommended vacuum and sealing upgrades by the manufacturer to decrease the dispersal of M. chimaera-containing aerosols into the operating room, despite hospital requests to the manufacturer. These findings highlight the need for continued awareness of the risk of M. chimaera infections associated with 3T HCDs, even if the devices are newly manufactured. Hospitals should maintain vigilance in adhering to FDA recommendations and the manufacturer's protocols and in identifying patients with potential M. chimaera infections with exposure to these devices.

Deuterated dextromethorphan/quinidine for agitation in Alzheimer's disease.

Deuterated dextromethorphan/quinidine for agitation in Alzheimer's disease.

Most Clinical Studies Do Not Report FDA Recommendations For Endpoints In NAFLD/NASH

PURPOSE: The aim of this study was to analyze whether clinical studies using exercise as an intervention strategy for non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) report Food and Drug Administration (FDA) recommendations for endpoints. METHODS: All studies targeting NAFLD/NASH available on the clinical trials platform (CTP) from the National Library of Medicine (NLM) were analyzed. However, only relevant clinical studies using exercise as an intervention strategy were included. FDA recommends the following endpoints for interventions targeting NAFLD/NASH: (i) resolution of steatohepatitis and no worsening of liver fibrosis; or (ii) improvement in liver fibrosis and no worsening of steatohepatitis; or (iii) resolution of steatohepatitis and improvement in liver fibrosis greater than or equal to one stage. RESULTS: We identified 49 of 916 studies, but removed one that was duplicated, four that conducted a diet intervention, and two others involving either lifestyle modification or exercise training with liraglutide or pioglitazone and berberine. Further selection yielded 42 studies in which researchers enrolled 1886 (or planned to enroll 6365) adults and older adults (N: 23, 56%) from both sexes (N: 36, 89%). Interventions were predominantly characterized by aerobic exercise (N: 25, 61%) performed for 45.8 ± 23.0 minutes per day and 4.1 ± 2.5 days per week for 17.7 ± 28.9 weeks. Participants were randomly assigned (N: 28, 68%) in parallel designs (N: 32, 78%) with open label (N: 34, 83%) or double masking methods (N: 4, 10%). FDA recommends double-blind, placebo-controlled clinical trials for at least 48 to 72 weeks. Most studies (N: 26, 63%) described techniques to analyze steatosis and fibrosis recommended by FDA, but did not explore their criteria, while others (N: 14, 34%) did not follow recommendations; only one study (2%) fulfilled FDA criteria. Studies also satisfied only half of the items regarding objectives and methods proposed by the CONSORT checklist. For example, they neither described methods used to generate random assignments nor described how sample size was calculated. CONCLUSIONS: Most clinical studies do not report FDA recommendations for endpoints in non-alcoholic fatty liver disease and non-alcoholic steatohepatitis.

The Role of Patient-reported Outcomes and Medication Adherence Assessment in Patient-focused Drug Development for Solid Organ Transplantation.

The Role of Patient-reported Outcomes and Medication Adherence Assessment in Patient-focused Drug Development for Solid Organ Transplantation.

Race reporting and diversity in US food and drug administration (FDA) registration trials for prostate cancer; 2006\u20132020

BackgroundThere is significant racial disparity in prostate cancer (PCa) in terms of incidence, treatment, and outcomes. Racial diversity and compliance with FDA race reporting guidelines in PCa drug registration trials are unknown. We analyzed racial diversity and race reporting in drug licensing trials for PCa.MethodsNew drug authorizations for PCa from 2006 to 2020 were identified. The corresponding licensing trial publications were analyzed to check compliance with current FDA recommendations for race reporting. If race was unreported, the clinical trial report was analyzed to determine participant recruitment by race and lead the recruiting country.ResultsDuring the study period, 17 new drug registrations for the management of PCa involving ten unique drugs were identified. In total, 18,455 participants were included in FDA registration trials, of which 76.3% were white or Caucasian, 7.9% Asian, 2.9% Black or African American, 0.5% American Indian or Alaskan Native, 0.1% Native Hawaiian or other Pacific Islander, 1.8% other or multiple races and 10.5% unknown. 53% of trials reported race in the licensing publication, however of this only 55% met current FDA recommendations. When the race was unreported in the licensing publication, 88% of studies had further information in the clinical study report.ConclusionWe found a significant under-representation of non-white participants in FDA drug registration trials for PCa. Race reporting in licensing publication is inconsistent and both FDA and International Committee of Medical Journal Editors guidelines are not being universally followed. Given the disproportionality of the disease burden of PCa, recruitment of Black and other minority participants to trials should be a research priority.