Food And Drug Administration Website Research Articles

Pirtobrutinib: A novel non-covalent BTK inhibitor for the treatment of adults with relapsed/refractory mantle cell lymphoma.

To provide a comprehensive review of the pharmacokinetics, pharmacodynamics, safety, and efficacy of a new Food and Drug Administration (FDA) approved Bruton's tyrosine kinase inhibitor (BTKi), pirtobrutinib for relapsed/refractory mantle cell lymphoma (r/r MCL). A literature search was conducted through PubMed MEDLINE, ClinicalTrials.gov, and the FDA website (January 2018-January 2023) using the following key terms: lymphoma, non-covalent, Bruton's tyrosine kinase (BTK), and relapse. Relevant English language monographs, studies, and abstracts conducted in humans were reviewed and considered. Pirtobrutinib, a novel non-covalent BTKi, was granted accelerated approval for treatment of r/r MCL on January 27th, 2023, based on an open-label, multi-center phase 1/2 BRUIN trial. In phase l, 61 patients with r/r MCL received seven dose levels of pirtobrutinib (25-300 mg). There was no reported maximum tolerated dose or dose-limiting toxicities during this study period. In phase 2, 56 r/r MCL evaluable efficacy patients received pirtobrutinib 200 mg daily. The overall response rate (ORR) was 52% (95% CI 38-65). Additionally, patients who received a previous covalent BTKi, ORR was 52% (95% CI 38-66). Neutropenia was the most common adverse reaction reported as a grade 3 or higher. Pirtobrutinib has demonstrated safety and efficacy in heavily pre-treated adult patients with r/r MCL. Advantages of this drug include its usage in patients whose malignancy is resistant to current BTKi, tolerability, and response rate. Multiple clinical trials are underway to determine the efficacy of pirtobrutinib in other B-cell malignancies.

Use of Single-Arm Trials in FDA Approvals of Treatments in Relapsed or Refractory B-Cell Lymphoma

Background: Single-arm trials are commonly used to evaluate therapies targeting life-threatening or rare diseases (e.g., late-stage cancers that are relapsed or refractory to prior interventions). A number of oncology products supported by single-arm trials have been approved by the United States Food and Drug Administration (FDA). The draft guidance issued by the FDA on 24 March 2023 recommended key considerations for trial design and analysis when a single-arm trial is considered appropriate to support accelerated approval. The objective of this study was to assess how often anticancer drugs approved by the FDA were based on single-arm trials in a typical relapsed or refractory indication and to evaluate the quality of trial design and data leading to approvals. Methods: We reviewed past approvals between 2006 and 2023 listed on the FDA website, focusing on the indication of relapsed or refractory B-cell lymphoma. Of 11 approvals identified, eight were supported by single-arm trials and three were based on randomized controlled trials. Approvals based on single-arm trials were further investigated, and each trial was analyzed for the following criteria as recommended by the draft FDA guidance: 1) if the endpoint was based on response rate assessed using appropriate criteria; 2) if the sample size was sufficient to provide robust estimates of efficacy and safety profile; and 3) if the magnitude and duration of response were adequate. Results: Among the eight approvals based on single-arm trials, one was approved in 2017, one in 2018, and two each in 2020, 2021, and 2023. Three were chimeric antigen receptor T-cell (CAR-T) therapies and were granted regular approval; the other five were non-CAR-T therapies which were granted accelerated approval. The primary endpoints adopted by all the trials were overall response rates (defined as complete and partial responders) and duration of response determined by an independent review committee. The magnitude of overall response rates reported by most trials ranged from 48% to 72% (with more than 50% of them with a complete response); one trial reported an overall response rate of 29% with complete response rate of 13%. A minimal median follow-up of six months after response was achieved in all trials. The estimated median duration of response varied from 10.3 to 21.7 months, with three trials reporting medians not reached. Based on the trial description, the analysis population was pre-specified for the evaluation of efficacy, ranging from 68 to 192 participants. Conclusion: Submissions based on single-arm trials for oncology therapies in the relapsed and refractory setting tended to be well accepted by FDA for accelerated and regular approval when the key criteria of trial design and data quality were adequately met.

Evaluation of Artificial Intelligence-generated Responses to Common Plastic Surgery Questions.

Artificial intelligence (AI) is increasingly used to answer questions, yet the accuracy and validity of current tools are uncertain. In contrast to internet queries, AI generates summary responses as definitive. The internet is rife with inaccuracies, and plastic surgery management guidelines evolve, making verifiable information important. We posed 10 questions about breast implant-associated illness, anaplastic large lymphoma, and squamous carcinoma to Bing, using the "more balanced" option, and to ChatGPT. Answers were reviewed by two plastic surgeons for accuracy and fidelity to information on the Food and Drug Administration (FDA) and American Society of Plastic Surgeons (ASPS) websites. We also presented 10 multiple-choice questions from the 2022 plastic surgery in-service examination to Bing, using the "more precise" option, and ChatGPT. Questions were repeated three times over consecutive weeks, and answers were evaluated for accuracy and stability. Compared with answers from the FDA and ASPS, Bing and ChatGPT were accurate. Bing answered 10 of the 30 multiple-choice questions correctly, nine incorrectly, and did not answer 11. ChatGPT correctly answered 16 and incorrectly answered 14. In both parts, responses from Bing were shorter, less detailed, and referred to verified and unverified sources; ChatGPT did not provide citations. These AI tools provided accurate information from the FDA and ASPS websites, but neither consistently answered questions requiring nuanced decision-making correctly. Advances in applications to plastic surgery will require algorithms that selectively identify, evaluate, and exclude information to enhance the accuracy, precision, validity, reliability, and utility of AI-generated responses.

Cost of Drug Wastage From Dose Modification and Discontinuation of Oral Anticancer Drugs

Oral chemotherapy is often dispensed to patients as a 1-month supply, with pill dose and package size predetermined by the drug manufacturer; thus, changing the patient dosage may waste the remaining initial drug supply. The cost of pills wasted due to dose modification and discontinuation is often unreported. To estimate the cost of pill wastage due to dose modification and discontinuation for oral anticancer drugs that were recently approved by the US Food and Drug Administration (FDA) or that are commonly prescribed. This retrospective cross-sectional economic evaluation initially identified 26 oral anticancer drugs newly approved between January 1, 2020, and August 31, 2022, from the FDA website and the top 50 best-selling pharmaceuticals in 2021 abstracted from the Drug Discovery Trends website managed by Drug Discovery and Development. The monthly costs of each agent were extracted from the Micromedex RED BOOK database. The FDA package insert, and in some cases PubMed, of each identified drug and indication was searched (matching on trial registration number) for information on registration trials. Information extracted for each drug included the name of the drug approved, drug target, cost of the drug, number of pills per bottle, available strengths, indication, name of the trial, number of patients exposed to treatment drug, number of dose level reductions, median duration of treatment, percentage of patients who received dose reduction, and percentage of dose discontinuation. All variables included in calculations were derived from the package insert or original trial publication. The cost of wastage for selected oral anticancer drugs due to dose reduction or discontinuation and the percentage of wastage in comparison with the total cost of treatment. After removing duplicates, 22 oral anticancer medications were included in the study. Because some drugs had more than 1 indication, data from 35 clinical trials were analyzed. Eight of the medications (covering 9 indications) had pill strengths divisible at each dose-reduction level; thus the cost of reduction for these pills was assumed to be zero. Two medications did not allow for dose reduction. The median cost of wastage from dose reduction and discontinuation was $1750 (range, $43-$27 200), with a mean cost of $4290 (SD, $5720) per patient. The median percentage of wastage from the total cost of treatment was 1.04% (range, 0.04%-10.80%) with a mean of 1.78% (SD, 2.21%). This economic evaluation found that due to both the high cost per pill and limited pill strength availability, the mean cost of wastage associated with dose reduction or discontinuation was $4290 per patient. These results suggest that to reduce the financial burden for patients with cancer, regulatory bodies should enforce availability of pill strengths that will limit pill wastage during dose modification or recommend that drug manufacturers issue credit for unused pills.

Food and Drug Administration novel drug decisions in 2017: transparency and disclosure prior to and 5 years following approval.

The Food and Drug Administration (FDA) approved 46 novel drugs in 2017. We reviewed availability of results prior to and during the 5 years following each approval. Using the FDA website and ClinicalTrials.gov, we recorded trials cited as evidence for the approval, total number of studies registered in ClinicalTrials.gov, number started and completed before approval, and the frequency and timing of reporting results. The 46 drugs approved in 2017 were evaluated in 1149 studies. The number of studies used to evaluate the 46 drugs ranged from 2 to 165 (mean: 24.98; SD = 28.95). Among these, an average of 9.22 studies (SD = 9.21) were started and 5.82 studies (SD = 6.89) were completed before the approval. A single trial justified approval for 19 of 46 (41%) of the approved products. Public posting of results prior to the FDA approval was available for an average of only 1.42 studies (SD = 3.12). No results were publicly reported before approval for 9 of the 46 drugs (20%). Health care providers and consumers depend on complete and transparent reporting of information about FDA-approved medications. Only a fraction of evidence from completed studies was available before approval and a substantial portion of research evidence remained undisclosed after 5 years.

Ubrogepant and rimegepant: signal detection using spontaneous reports of adverse events from the Food and Drug Administration Adverse Event Reporting System

ABSTRACT Background In this study, we fill this gap in knowledge by updating the safety profile of ubrogepant and rimegepant via disproportionality analysis in the Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS), a US-based database registering spontaneous reports. Research design and methods ASCII files of quarterly extraction of FAERS data were downloaded from the FDA website up to the 3rd quarter (Q3) of 2021 (last accessed 03/02/2022). Disproportionality analysis was done using the Reporting Odds Ratio (ROR) as a disproportionality measure. RORs of all AEs related to ubrogepant and rimegepant in FAERS were calculated in comparison with those related to erenumab. Drug-event pairs with a frequency ≤ 2, were removed according to European Medicine Agency (EMA)’s procedures. Results In total, 2010 and 3691 individual case safety reports (ICSRs) recorded in FAERS reported ubrogepant and rimegepant, respectively, as suspect drugs. Ten disproportionality signals for ubrogepant and 25 disproportionality signals for rimegepant were identified; these were mostly related to psychiatric, neurological, gastrointestinal, skin, vascular, and infectious type of adverse events. Conclusions New safety aspects related to the treatment of ubrogepant and rimegepant using disproportionality analysis from spontaneous reporting databases were identified. Further studies are needed to confirm these findings.

Regulatory approvals and survival benefit for novel lymphoma drugs from 2013–2022

Increasingly, novel agents are approved for the treatment of lymphoma by the US Food and Drug Administration (FDA) via accelerated approval and using single arm trials and surrogate efficacy measures, which leave uncertainty as to their clinical benefit. Methods: We reviewed the FDA website and [email protected] to identify approvals, conversions and withdrawals of novel agents for lymphoma from 2013 to 2022. From FDA approval summaries, we collected efficacy outcomes for pivotal trials, trial design, and type of approval (accelerated or regular). We extracted confirmatory trial characteristics and results from PubMed. Results: The FDA approved 19 novel drugs and 4 cellular therapies across 38 lymphoma indications. 25 (66%) indications received accelerated approval. All initial approvals were based on changes to surrogate measures: 7 (18%) on progression-free survival, 11 (29%) on overall response rate (ORR) plus duration of response, and 20 (53%) on ORR alone. 27 (71%) indications were approved based on single arm trials (22 accelerated, 5 regular). Just 6 (16%) indications have shown overall survival (OS) benefit in randomized trials. Of 25 accelerated approval indications, 4 (16%) have been converted, while 4 have been withdrawn due to toxicity (all Pi3K inhibitors). Conclusions: Many lymphoma therapies are FDA-approved based on single-arm trials and surrogate measures, while few have confirmed OS benefit. Timely randomized trials with meaningful clinical endpoints can help patients and clinicians choose among therapeutic options. The research was funded by: Arnold Ventures Keyword: Therapeutics and Clinical Trials in Lymphoma Conflicts of interests pertinent to the abstract. E. R. S. Cliff Research funding: Arnold Ventures W. B. Feldman Research funding: Arnold Ventures A. S. Kesselheim Research funding: Arnold Ventures

Review and assessment of the donor safety among plasma donors.

Review and assessment of the donor safety among plasma donors.

Assessing Readability of FDA-Required Labeling for Breast Implants

Abstract Goals/Purpose In 2021, the United States (US) Food and Drug Administration (FDA) introduced regulations to improve the delivery of breast implant patient education, including new labeling requirements. The new regulations called for a patient decision checklist to be reviewed with a physician ahead of surgery. To ensure educational materials are accessible to most patients, the National Institutes of Health recommend they be written at a sixth to seventh grade level. This study aims to assess the readability of patient-facing FDA labeling for breast implants. Methods/Technique Eleven patient information brochures and seven patient decision checklists were obtained from four breast implant company websites. An example checklist was also obtained from the FDA website. Plain text was extracted from each of the documents. Figures, tables, references, and indices were omitted. The text files were analyzed using four measures of readability validated in clinical materials: Flesch-Kincaid Grade Level, Coleman-Liau Index, Simplified Measure of Gobbledygook (SMOG), and Automated Readability Index (ARI). Results/Complications On average, patient information brochures were 73 pages long (range: 48-92) and included 8 figures or graphics, while patient decision checklists were 5.7 pages long (range: 4-7) and included 0 figures or graphics. Mean readability scores of brochures were a Flesch-Kincaid of 12.7, Coleman-Liau Index of 13.0, SMOG of 14.0, and ARI of 12.7, with an overall mean grade level of 13.1 (13th grade). For decision checklists, results showed a Flesch-Kincaid of 14.2, Coleman-Liau Index of 13.3, SMOG of 15.6, and ARI of 14.8, with an overall grade level of 14.5 (14-15th grade). Comparatively, the sample decision checklist published by the FDA had a Flesch-Kincaid of 13.9, Coleman-Liau Index of 13.0, SMOG of 15.5, and ARI of 14.4, with an overall grade level of 14.2 (14th grade). Conclusion Although patient decision checklists were introduced to improve accessibility of breast implant educational materials, the level at which they are written exceeds the recommendation for the average US adult by several grade levels, suggesting that patients may not fully understand current materials. While shorter than the comprehensive information brochures available, decision checklists were more difficult to read across all readability scales assessed in this study, and neither brochures nor checklists met recommended reading levels on any of the assessed scales. In order to encourage patient understanding of surgical and implant risks and promote the positive health outcomes, the FDA and breast implant companies may consider revising labeling materials.

396 Quantitative Analysis of FDA Warning Letters Related to the Use of Social Media Sites in Product Misbranding for the Treatment, Prevention, or Diagnosis of COVID-19

OBJECTIVES/GOALS: Food and Drug Administration (FDA) warning letters regarding misbranding of products intended to treat, prevent, or diagnose COVID-19 were used as a proxy for assessing misinformation on social media. The FDA database of Warning Letters was used to identify the largest misinformation contributor. METHODS/STUDY POPULATION: On November 9, 2022, the full dataset of warning letters dating back to January 1, 2018 was extracted from the FDA website. Separate datasets were also extracted using the search terms: Facebook’, Twitter’, YouTube’, and Instagram’. The data entries were organized by issuing office and subject. The subjects were then filtered to only include letters related to misbranding of products for COVID-19. Letters regarding medical devices, manufacturing practices, and adulterated products were excluded from the analysis. Cumulative totals were collected for the number of letters issued for each search term. These totals were stratified by year and scaled by platform size for relative comparison. RESULTS/ANTICIPATED RESULTS: The FDA’s Center for Drug Evaluation and Research issued the most letters related to misbranding of COVID-19 products, 153 out of the 2798 entries in the complete dataset. Analysis of the datasets by search term show: 53, 18, 24, and 17 letters were related to Facebook, Twitter, YouTube, and Instagram respectively. Forty-one letters were related to other non-social media sources. Facebook had the most letters issued, however when scaled to account for the size of each respective platform’s approximate user base, Twitter had the largest proportional amount of misinformation regarding agents for the management of COVID-19, followed by Facebook, then Instagram. Most letters were issued in 2020. DISCUSSION/SIGNIFICANCE: In light of COVID-19, many social media sites adopted policies to limit inaccurate information. The success of these efforts have been variable. Although Facebook is the largest absolute contributor assessed, greater attention should be given to the policies of other platforms utilized by the industry.

Safe Technical Innovation: Development and Implementation of a Robotic Breast Operation Program.

Safe Technical Innovation: Development and Implementation of a Robotic Breast Operation Program.

Cost per Event Averted in Cancer Trials in the Adjuvant Setting From 2018 to 2022

Adjuvant therapies are often approved based on improvements in disease-, progression-, or relapse-free survival (ie, an event). An important estimate in adjuvant therapies is the cost per event averted. To characterize the costs per event averted of anticancer drugs approved by the US Food and Drug Administration (FDA) between January 2018 and March 2022. In this cross-sectional study, all approvals were reviewed from the FDA website. Approvals selected for the analysis needed to be drawn from randomized trials involving anticancer drugs studied in the adjuvant treatment of solid tumors. Treatments of nonsolid tumors; nonrandomized, noncontrolled trials; and unpublished trials were excluded. Approvals between January 2018 and March 2022 were included, and 11 trials met inclusion criteria. The monthly costs of each agent were abstracted from the Micromedex RED BOOK database. All variables included in calculations were derived from the original trial publication. Information abstracted for each approval included the name of the drug approved, name of the trial, primary end point, dosing regimen in the trial, median duration of treatment, tumor type, monthly costs per drug, and the number needed to treat for the primary end point. Data were analyzed in March 2022. The cost per event averted for each agent studied in each clinical trial; the monthly cost of each drug, the cost per patient for each drug, the primary clinical end point studied in each trial; the study's design and setting. A total of 11 approvals were included in the study. From January 2018 to March 2022, all approvals were based on a surrogate end point as the primary end point, with no trials demonstrating, to date, an overall survival benefit. The median cost per event averted of drugs in the adjuvant setting was $1 610 000 (range, $820 000 to $2 640 000). The median cost of a complete adjuvant treatment was $158 000 per patient. In this cross-sectional study, anticancer agents in the adjuvant setting were approved based on disease-, progression-, event-, or relapse-free survival. Costs per event averted were high. These findings suggest that these drugs may not achieve wide or global use unless their efficacy improves or their prices decrease.

Efficacy, safety and cost of gene therapy medicinal products in the U.S. and Europe.

Gene or advanced therapy medicinal products (ATMPs) are evolving innovative products that have recently been attracting medical and healthcare attention. ATMPs are offering advanced techniques in treating certain conditions, including rare diseases. Meanwhile, the short- and long-term safety and efficacy of these products raise concerns. In this study, a comparative analysis of gene therapy medicinal products in the U.S. and E.U. was carried out to provide an overview of their efficacy and safety. Data up until 2019 were collected from the Food and Drug Administration (FDA) and European Medicines Agency (EMA) regarding approved gene therapy products. The FDA and EMA websites and published clinical trials were searched to extract the required information. A total of eight gene therapies were identified that had been approved in the U.S. and/or E.U. These products are approved to treat various health conditions in different populations. Their efficacy and safety were evaluated on the basis of completed and ongoing pivotal clinical trials. ATMPs offer potential management for genetic disorders and rare health conditions that are untreatable. However, one of the main concerns associated with these therapies is the small sample size that is included in the pivotal clinical trials. The uncertain efficacy, incomplete trials and serious adverse events could be challenges that make some of these products a last-line therapy.

Clinical Pharmacology of Entacapone (Comtan) From the FDA Reviewer.

This new drug application was first submitted to the US Food and Drug Administration (FDA) by the Orion Corporation from Finland on January 2, 1998. The final clinical pharmacology review was completed on September 3, 1999. Entacapone is a potent and specific peripheral catechol-O-methyltransferase inhibitor. It has been shown to improve the clinical benefits of levodopa plus an aromatic L-amino acid decarboxylase inhibitor when given to patients with Parkinson's disease and end-of-dose deterioration in the response to levodopa (the "wearing-off" phenomenon). The drug indication is for Parkinson's disease as an adjunct therapy to levodopa/carbidopa. This is a combination drug with carbidopa (aromatic amino acid decarboxylation inhibitor) and entacapone. It is rapidly absorbed after oral administration of a single dose, with peak time generally reached within 1 hour. It is noted that no accumulation of plasma entacapone was detected after 8 daily doses. The maximum daily dose is 2000 mg. In this paper, the clinical pharmacology review of the drug is presented from the perspective of a clinical pharmacologist who reviewed this new drug application at the FDA. It should be noted that all the information in this paper is publicly available on the FDA website and in its literature.

Response rate of anticancer drugs approved by the Food and Drug Administration based on a single-arm trial

BackgroundIn recent years, an increasing number of anticancer drugs have been approved based on the results of a single-arm trial (SAT). The magnitude of the objective response rate (ORR) in SATs is important for regulatory decisions, but there has been no clear guidance specifying the degree of ORR for approval.MethodsAll anticancer drugs approved by the US Food and Drug Administration (FDA) between January 2016 and December 2019 were identified through the FDA website. From these, we selected drugs approved for solid tumors based on SATs. For each indication, one regimen was selected from the standard-of-care as the best comparison therapy (BCT), which was defined as the latest regimen for the same tumor and treatment line. We compared the ORR of the investigated product with that of the BCT.ResultsOf the 31 solid tumor indications identified, we selected BCT for 28. In 23 of the 28 indications (82.1%), the ORR of the investigated product exceeded that of the BCT, and in 16 of these (69.6%), the lower limit of the 95% confidence interval (CI) of the ORR of the investigated product exceeded the point estimate of the BCT ORR. For seven products, the lower limit of the 95% CI was below the point estimate of the BCT ORR, with differences ranging from 1.0% to 3.4%.ConclusionThe lower limit of a 95% CI of the ORR of a new drug in an SAT exceeding the point estimate of the BCT ORR could be an important factor in obtaining regulatory approval.

Spinal Cord Stimulators: Patient Safety and Adverse Outcomes from Imaging

<h3>Research Objectives</h3> A literature review of the current recommendation for SCS compatibility with MR imaging and a review of the Food and Drug Administration (FDA) approved spinal cord stimulation systems were performed. <h3>Design</h3> The literature review was completed using PubMed, the FDA website (www.fda.gov), and the SCS manufacturers' websites. <h3>Setting</h3> N/A. <h3>Participants</h3> N/A. <h3>Interventions</h3> N/A. <h3>Main Outcome Measures</h3> Is the usage of MRI safe in patients with spinal cord stimulators (SCS)? <h3>Results</h3> The current recommendations, composed on the basis of evidence-based medicine, reveal close adherence of an MRI with a 1.5T magnet and a mean total body specific absorption rate (SAR) of 0.9 W/kg or below which can promote patient safety and satisfaction, despite the variability between different SCS manufacturers1. Measurement of safety includes tearing of tissues due to rotational force generated by the magnetic field, acceleration of the device towards the bore of the magnet ("missile effect"), and burns caused by overheating of the device. <h3>Conclusions</h3> Strict adherence to an MRI with a 1.5T magnetic bore core and a SAR of 0.9 W/kg or below can promote patient safety despite the various SCS developed by manufacturers. Providers and technicians should be encouraged to seek specific SAR and Slew Rate and Field Strength conditions found on the manufacturers' website to yield the highest safety index and optimal image quality. <h3>Author(s) Disclosures</h3> None.

Experience with COVID-19 convalescent plasma provides vital guidance to future pandemics.

Experience with COVID-19 convalescent plasma provides vital guidance to future pandemics.

A Trans-Governmental Collaboration to Independently Evaluate SARS-CoV-2 Serology Assays.

ABSTRACTThe emergence of SARS-CoV-2 created a crucial need for serology assays to detect anti-SARS-CoV-2 antibodies, which led to many serology assays entering the market. A trans-government collaboration was created in April 2020 to independently evaluate the performance of commercial SARS-CoV-2 serology assays and help inform U.S. Food and Drug Administration (FDA) regulatory decisions. To assess assay performance, three evaluation panels with similar antibody titer distributions were assembled. Each panel consisted of 110 samples with positive (n = 30) serum samples with a wide range of anti-SARS-CoV-2 antibody titers and negative (n = 80) plasma and/or serum samples that were collected before the start of the COVID-19 pandemic. Each sample was characterized for anti-SARS-CoV-2 antibodies against the spike protein using enzyme-linked immunosorbent assays (ELISA). Samples were selected for the panel when there was agreement on seropositivity by laboratories at National Cancer Institute’s Frederick National Laboratory for Cancer Research (NCI-FNLCR) and Centers for Disease Control and Prevention (CDC). The sensitivity and specificity of each assay were assessed to determine Emergency Use Authorization (EUA) suitability. As of January 8, 2021, results from 91 evaluations were made publicly available (https://open.fda.gov/apis/device/covid19serology/, and https://www.cdc.gov/coronavirus/2019-ncov/covid-data/serology-surveillance/serology-test-evaluation.html). Sensitivity ranged from 27% to 100% for IgG (n = 81), from 10% to 100% for IgM (n = 74), and from 73% to 100% for total or pan-immunoglobulins (n = 5). The combined specificity ranged from 58% to 100% (n = 91). Approximately one-third (n = 27) of the assays evaluated are now authorized by FDA for emergency use. This collaboration established a framework for assay performance evaluation that could be used for future outbreaks and could serve as a model for other technologies.IMPORTANCE The SARS-CoV-2 pandemic created a crucial need for accurate serology assays to evaluate seroprevalence and antiviral immune responses. The initial flood of serology assays entering the market with inadequate performance emphasized the need for independent evaluation of commercial SARS-CoV-2 antibody assays using performance evaluation panels to determine suitability for use under EUA. Through a government-wide collaborative network, 91 commercial SARS-CoV-2 serology assay evaluations were performed. Three evaluation panels with similar overall antibody titer distributions were assembled to evaluate performance. Nearly one-third of the assays evaluated met acceptable performance recommendations, and two assays had EUAs revoked and were removed from the U.S. market based on inadequate performance. Data for all serology assays evaluated are available at the FDA and CDC websites (https://open.fda.gov/apis/device/covid19serology/, and https://www.cdc.gov/coronavirus/2019-ncov/covid-data/serology-surveillance/serology-test-evaluation.html).

A Review of Patient-Reported Outcome Labeling of FDA-Approved New Drugs (2016-2020): Counts, Categories, and Comprehensibility

ObjectivesA review of new drug approvals (NDAs) by the US Food and Drug Administration (FDA) for 2006 to 2015 showed that approximately 20% of new drugs had labeling based on patient-reported outcomes (PROs). The purpose of this study was to review labeling text based on PRO endpoints for NDAs from 2016 to 2020, with a special focus on the comprehensibility of such statements when included. MethodsWe reviewed drug approval reports on the Drugs@FDA web page of the FDA website to determine the number of NDAs from 2016 to 2020. For all identified NDAs, drug approval package and product labels were reviewed. NDAs from 2016 to 2020 were grouped by disease category as per International Classification of Diseases 10th Revision. Data were summarized for diseases that traditionally rely on PROs for evaluating treatment benefit (PRO dependent) and for diseases that traditionally do not rely on PROs (non-PRO dependent). Results were compared with NDAs from 2006 to 2010. ResultsNDAs amounting to 228 were identified from 2016 to 2020, 26.3% of which had labeling statements based on PRO endpoints. From 2006 to 2015 and from 2016 to 2020, PRO labeling statements were included in 46.5% (46 of 99) and 50.0% (47 of 94), respectively, of NDAs for PRO-dependent new molecular entities and in 6.0% (12 of 199) and 9.7% (13 of 199), respectively, of NDAs for non–PRO-dependent new molecular entities. Comprehensibility of labeling statements based on PRO endpoints was judged to be complex in 56.7% of product labels. ConclusionsThe increase in labeling text based on PRO endpoints in product labels is encouraging. However, there is room for improvement on the comprehensibility of labeling statements based on PRO endpoints.

Social Media Discussions on the FDA’s Modified Risk Tobacco Product Authorization of IQOS

Background: The U.S. Food and Drug Administration (FDA) authorized the marketing of the IQOS tobacco heating system as a modified risk tobacco product (MRTP) in July 2020, permitting its ‘reduced exposure’ marketing. This decision is accompanied by much controversy among the global health community. We provide a preliminary analysis of Twitter conversations regarding the MRTP authorization of IQOS by identifying the authors, valence towards the policy decision, source of cited link, and focused topic. Methods: We analyzed 548 tweets mentioning MRTP posted between July 2016 (when PMI submitted the proposal) and October 2020. Results: We found a higher proportion of pro-MRTP valence (25.4%) than anti-MRTP (16.2%). Nearly half of the tweets (47.2%) expressing personal opinions presented pro-MRTP valence (vs. anti-MRTP = 23.9%). The FDA website was more frequently cited in pro-MRTP tweets (30.8% vs. anti = 4.8%), while tobacco control advocates’ websites were cited only in anti-MRTP tweets (77.4% vs. pro = 0). Pro-MRTP valence appeared more frequently in tweets mentioning health (53.1% vs. anti =38.5%) and cessation (100% vs. anti = 0). Nearly 42% of tweets showed a bot score greater than .43, indicating a possibility of automation. Conclusion: Continuous efforts are needed to surveil the industry’s attempts to create a climate of false consensus and circulate misinformation regarding MRTP on social media, as well as to assist non-scientific audiences’ understanding of MRTP.