FDA Communication Research Articles

Industry Update, October 2022.

Industry Update, October 2022.

The impact of the 2011 US Food and Drug Administration transvaginal mesh communication on utilization of synthetic mid-urethral sling procedures

We sought to examine the change in utilization of the midurethral sling (MUS) for the treatment of stress urinary incontinence (SUI) after the 2011 US FDA communication regarding transvaginal mesh. This is a retrospective cohort study evaluating surgical utilization of MUS at a managed care organization of 4.5 million patients from 2008 to 2016. The primary outcome was the change in utilization of synthetic mesh MUS before and after the July 2011 FDA communication. Secondary outcomes were the changes in surgeon level MUS utilization. MUS procedures decreased from 131 to 116 per 100,000 adult women with a decrease of 11.5% from 2010 to 2012. Year over year utilization of MUS was rapidly increasing (p < 0.01) prior the FDA communication from 116 (in 2008) to 131 (in 2010) per 100,000 women and then significantly declined (p < 0.01) after its release from 135 (in 2011) to 75 (in 2016) per 100,000 women (13% increase vs 44% decrease). The number of surgeons performing MUS increased (p < 0.01) from 172/year to 186/year from 2008 to 2010 (Table 1). This decreased (p < 0.01) from 183/year to 121/year from 2011 to 2016. MUS for SUI drastically declined after the FDA communication. Despite the 2011 FDA communication concerning only transvaginal mesh for pelvic organ prolapse, there was a significant decrease in MUS with synthetic mesh utilization. Our findings support the importance of continued long-term outcome data regarding the safety and efficacy of MUS and highlight the impact of the FDA warning on MUS utilization.

FDA postmarketing safety labeling changes: What have we learned since 2010 about impacts on prescribing rates, drug utilization, and treatment outcomes.

Prior literature reviews have identified gaps in understanding of how postmarketing safety labeling changes and related FDA communications impact key clinical and behavioral outcomes. We conducted a review of newly published studies on this topic to determine what new evidence exists and to identify which gaps may still remain. We believe that this information can support FDA as it develops and implements future risk communication approaches. We searched PubMed and Embase for studies published between January 1, 2010, and August 7, 2017 that examined the impact of labeling changes or associated FDA safety-related communications. For each study, we extracted information on research design and findings for key clinical outcomes and behaviors. We also conducted a ROBINS-I review to identify potential for bias in the research design of each study. We found that the estimated impacts of FDA labeling changes on several key outcomes-including adverse events-varied. Labeling changes also yielded unintended consequences on drug prescribing in some cases, despite low provider adherence. Finally, some studies we reviewed exhibited potential for bias due to confounding, among other factors. The new studies we reviewed contain many of the same limitations identified in previously published reviews. While there are several challenges to conducting this research there is substantial room for improvement in the quality of the evidence base. More information, particularly with respect to the types of populations and medications affected by labeling changes, is needed to support the development of more effective and targeted safety communications.

PCN506 MUTATION TESTING AND TREATMENT OF THE MOST COMMON ONCOLOGY DISEASES IN GERMANY: ANALYSIS OF AN ONCOLOGY EMR DATABASE

The role of real-world evidence (RWE) in healthcare decision-making is constantly growing, acknowledged by recent FDA and EMA communications. Especially in oncology, a better understanding of the real-world treatment of patients is needed, both to compare RWE with clinical trial results and to identify unmet needs in the real-world (RW) treatment of patients. However, there is a lack of reliable data in this respect. We aimed to describe the RW treatment of patients included in a new electronic medical record databank targeting German oncology patients (INGRESS-Indivumed Liquid Biopsy RWE oncology database). The databank is built based on German outpatient oncology cases, it currently includes 14,145 oncology patients. It provides data on patient and disease characteristics, treatments, diagnostics including mutation/immunohistochemistry testing, and clinical outcomes; furthermore, for each patient blood draws for an ex-post mutation testing are available. Most common cancer types in the database are breast cancer (BC), lung cancer (LC) and colon cancer (CC), with a proportion of 23.8%, 11.7% and 8.8%, respectively. The average age was 66.5 years in the overall sample (60.9/67.2/68.0 years in BC/LC/CC patients). Percentage of females was 56.3% (98.0%/40.6%/44.9%). A mutation/immunohistochemistry test was conducted in 98.9% of the patients with BC (54.6% of patients with HER2+). Proportion of tested patients was 66.0%/55.9% in LC/CC. Most common mutation types in LC were PD-L1 and EGFR+ (53.0%/12.1% of tested LC patients) and KRAS in CC (42.5%). The most frequently prescribed 1L treatment was paclitaxel in BC patients with/without HER2+, pembrolizumab in LC patients with PD-L1, carboplatin in non-PD-L1 LC patients, and irinotecan+folinic acid in KRAS+/non-KRAS CC patients. The Indivumed Liquid Biopsy RWE oncology database has the potential to provide valuable insights into RW data on the treatment and treatment-associated outcomes of German oncology patients.

1447 FDA Notice on Transvaginal Energy-Based Devices (TV-EBD) for Laser Vaginal Therapy: Was it Justified?

Study Objective Our aim in this study was to shed light on the origin of evidence for reported adverse events detailed in the Manufacturer and User Facility Device Experience (MAUDE) given by the FDA communication regarding the use of laser vaginal device therapy. Design The MAUDE database was queried from 2010-2018 for adverse events related to manufacturers who currently offer laser vaginal therapy devices. Each adverse event was then categorized based on the details of the event as device error, provider error, a common risk, patient-reported lack of efficacy, or a procedure related adverse event. Additionally, social media outlets such as Twitter were reviewed to gather public opinion on laser vaginal therapy in response to the recent FDA communication. Setting N/A. Patients or Participants N/A. Interventions N/A. Measurements and Main Results A total of 40 adverse events were reported on the MAUDE database regarding laser vaginal therapy devices in the queried time frame. Of that 40, 27 were unique events, while the other 13 were duplicate reports. Of the 27, 12 were categorized as patient-reported lack of efficacy, 8 were provider error, 3 were device error, 2 were common risk, and 2 were, with the provided information in MAUDE, procedure related AEs. Social media responses revealed largely negative opinions on laser vaginal therapy devices. Conclusion Many of the reported adverse events on the MAUDE database revealed a fundamental lack of education, either to the providers, or to the patients, on the efficacy of laser vaginal therapy. Almost half of the total individual reports to MAUDE (12) were patients with previous medical histories regarding vaginal dryness, incontinence or sexual dysfunction reporting continued lack of improvement. These reports support the concern of miscommunication with device manufacturer. As with any medical treatment, in-depth consultation with a professional help reduce any procedural risk.

Autologous rectus fascia sling for treatment of stress urinary incontinence in women: A review of the literature.

Stress urinary incontinence (SUI) is common in the adult females. Surgical treatment options include synthetic mid-urethral sling (MUS), autologous sling, bulking agents, and Burch colposuspension. The autologous pubovaginal sling (PVS) has re-emerged in response to complications of synthetic MUSs and FDA communications regarding the use of vaginal mesh. This resulted in patients' fear related to vaginal mesh and drop in number of patients seeking surgical treatment of SUI. PVS has re-emerged as an option for treatment of primary SUI. The aim of this review is to familiarize, disseminate information, and share tips for the practicing female pelvic surgeons related to the practice of the autologous fascia sling. We reviewed the literature related to the autologous sling. We used the following data bases and search engines: GoPubMed (Transinsight), Cochrane reviews (Wiley Interscience), google scholar (google), and Scopus (Elsevier). Because it is the most commonly investigated and utilized, we focused on the autologous rectus fascia sling. We also focused on the retropubic sling approach because the literature on transobturator rectus fascia sling is sparse. Out of 307 articles related to the subject found, 22 articles were included and the rest were excluded. ARFS is a valid primary method of treatment for female SUI. Also, it is used in particular indications such as patients with intrinsic sphincter deficiency (ISD), prior pelvic irradiation, failed and/or complicated synthetic MUS, and violated urethral lumen.

Do Health Care Professionals See FDA's Communications?

Dr. Hyman is Professor Emeritus, Department of Biomedical Engineering, Texas A&M University, College Station, TX; E-mail: [email protected].

Surgical interventions and anesthesia in the 1st year of life for lower urinary tract obstruction

BackgroundPatients with a prenatal diagnosis of lower urinary tract obstruction (LUTO) may undergo prenatal interventions, such as vesicoamniotic shunt (VAS) placement, as a temporary solution for relieving urinary tract obstruction. A recent FDA communication has raised awareness of the potential neurocognitive adverse effects of anesthesia in children. We hypothesized as to whether a prenatal LUTO staging system was predictive of the number of anesthesia events for prenatally diagnosed LUTO patients. MethodsWe retrospectively reviewed the prenatal and postnatal clinical records for patients with prenatally diagnosed LUTO from 2012 to 2015. Patients were stratified by prenatal VAS status and by LUTO disease severity according to Ruano et al. (Ultrasound Obstet Gynecol. 2016). Results31 patients were identified with a prenatal LUTO diagnosis, and postnatal records were available for 21 patients (seven patients in each stage). When combining prenatal and postnatal anesthesia, there was a significant difference in the number of anesthesia encounters by stage (1.6, 3.7, and 6.7 for Stage I, II, and III respectively, p = .034).Upon univariate analysis, higher gestational age (GA) at birth was associated with a decreased number of anesthesia events in the first year (p = .031). ConclusionsThe majority of infants with prenatally diagnosed LUTO will undergo postnatal procedures with general anesthesia exposure in the first year of life. Patients with higher prenatal LUTO severity experienced a higher number of both prenatal and postnatal anesthesia encounters. In addition, higher GA at birth was associated with fewer anesthesia encounters in the first year. Level of evidenceThis is a prognostic study with Level IV evidence.

2018

OBJECTIVES/SPECIFIC AIMS: Translating conventional and regenerative medicine strategies from the research laboratory into the clinic is a complex process that can delay bringing novel therapies to the patient. Navigating the increasingly complex regulation surrounding cell-based and combination product technologies is a major challenge for the translational biomedical scientist. To this end, Mayo Clinic created a new position, the “Translational Integrator,” as part of the cGMP Biomaterials Facility in the Center for Regenerative Medicine. METHODS/STUDY POPULATION: The Translational Integrator educates investigators about FDA standards and regulatory pathways; determines where the product is on the translational spectrum; works to understand the science behind the product; determines what additional studies may be needed; supports investigators in preparing for FDA communications and submissions; and educates researchers about institutional resources and funding mechanisms needed to move their product into manufacturing and trials. A primary objective is to meet investigators at an early stage in product development to avoid conducting potentially redundant work to meet regulatory requirements. RESULTS/ANTICIPATED RESULTS: Robust training in clinical and translational research methodology enables the integrator to facilitate the collaboration necessary between investigators, clinicians, institutional resources, regulators and funders to move products towards FDA IND/IDE approval and first-in-human trials. It is an iterative process using technology/translational readiness criteria, project management and review by subject matter experts that is highly interactive and customized to each project. Current projects include topics in orthopedic surgery and ENT. In creating and refining this position, several key lessons have been learned. DISCUSSION/SIGNIFICANCE OF IMPACT: First, the Translational Integrator must undergo constant reflection and assessment of investigator needs, which requires flexibility and understanding that their role may change in the context of each product. Second, the support that the Translational Integrator provides can shift the mindset of the investigator from being averse to engaging in the translational process to eager to move their product forward. Finally, for the investigator who does not personally want to move their work into first-in-human trials, establishing connections to intellectual property generation and licensing may support movement of their findings into patients.

Level of Evidence Associated with FDA Safety Communications with Drug Labeling Changes: 2010-2014

Purpose: Approximately 800,000 safety reports are submitted to the FDA annually, however, only significant issues generate drug safety communications (DSC). The purpose of this study was to determine the type of clinical evidence used to warrant a change in drug labeling for drugs with DSC between January 1, 2010 and December 31, 2014. Methods: Selected data was obtained from the FDA website. The primary endpoint of the study was the frequency of the types of clinical evidence used in FDA communications, as reported through the FDA DSC. Results were evaluated via descriptive statistics, and chi-squared for nominal data. Results: A total of 2521 drug safety labeling changes were identified and 99 (3.9%) of safety communications met the inclusion criteria. The majority of the labeling changes were associated with single agents (83.8%). The three most frequently reported labeling changes were warnings (68.7%), precautions (58.6%), and patient package insert/medication guide (23.2%). Case reports resulted in the greatest number of documented literature types (n = 791), followed by randomized controlled trials (n = 76), and case control/cohort studies (n = 74). Significantly more evidence for DSCs were classified as Level of Evidence B (LOE B, 68.6%), compared to LOE A (17.1%), and LOE C (14.1%) (p = 0.007). Conclusions: The majority of drug labeling change initiators was associated with LOE equivalent to B. Practitioners should evaluate data associated with labeling changes to determine how to interpret the information for their patients.&#x0D; Conflict of Interest&#x0D; We declare no conflicts of interest or financial interests that the authors or members of their immediate families have in any product or service discussed in the manuscript, including grants (pending or received), employment, gifts, stock holdings or options, honoraria, consultancies, expert testimony, patents and royalties.&#x0D; &#x0D; Type: Original Research

Level of Evidence Associated with FDA Safety Communications with Drug Labeling Changes: 2010-2014

Purpose: Approximately 800,000 safety reports are submitted to the FDA annually, however, only significant issues generate drug safety communications (DSC). The purpose of this study was to determine the type of clinical evidence used to warrant a change in drug labeling for drugs with DSC between January 1, 2010 and December 31, 2014. Methods: Selected data was obtained from the FDA website. The primary endpoint of the study was the frequency of the types of clinical evidence used in FDA communications, as reported through the FDA DSC. Results were evaluated via descriptive statistics, and chi-squared for nominal data. Results: A total of 2521 drug safety labeling changes were identified and 99 (3.9%) of safety communications met the inclusion criteria. The majority of the labeling changes were associated with single agents (83.8%). The three most frequently reported labeling changes were warnings (68.7%), precautions (58.6%), and patient package insert/medication guide (23.2%). Case reports resulted in the greatest number of documented literature types (n = 791), followed by randomized controlled trials (n = 76), and case control/cohort studies (n = 74). Significantly more evidence for DSCs were classified as Level of Evidence B (LOE B, 68.6%), compared to LOE A (17.1%), and LOE C (14.1%) (p = 0.007). Conclusions: The majority of drug labeling change initiators was associated with LOE equivalent to B. Practitioners should evaluate data associated with labeling changes to determine how to interpret the information for their patients. Conflict of Interest We declare no conflicts of interest or financial interests that the authors or members of their immediate families have in any product or service discussed in the manuscript, including grants (pending or received), employment, gifts, stock holdings or options, honoraria, consultancies, expert testimony, patents and royalties. &nbsp; Type:&nbsp;Original Research

MP10-19 TRENDS AND FAILURE RATES IN THE MEDICAL TREATMENT OF PELVIC ORGAN PROLAPSE FOR MEDICARE PATIENTS

INTRODUCTION AND OBJECTIVES: The efficacy of transvaginal mesh for anterior colporrhaphy is well established (Nguyen 2008); however, complications related to use of transvaginal mesh led to the release of FDA safety communications in 2008 and 2011. This led to a significant decrease in the use of transvaginal mesh for pelvic organ prolapse (POP) since 2011 (Clemens 2013). We hypothesized that the decrease in transvaginal mesh use was partly driven by increased patient awareness of complications. We tested this using Google Trends , a public tool that provides data on temporal patterns of search terms and correlated this data with the timing of the FDA communications. METHODS: Weekly relative search volume (RSV) was obtained from Google Trends using the search term 00transvaginal mesh00, with higher RSV indicating an increase in search volume. These were divided into three groups: 2005 to July 13th 2011 (the date of the second FDA communication), a six-month period following the update, and thereafter until June 6th 2015. The distribution of the weekly RSV over the three periods was tested using one-way analysis of variance. We also tested the difference between total number of web pages containing 00transvaginal mesh00 (reported annually by Google) between 2006-2010 versus 2011-2015 using a paired t-test. RESULTS: The mean RSV prior to the 2011 FDA communication was 0.73 [standard deviation (SD)1⁄46.6], compared to 29.9 (SD1⁄417.0) in the six months after the update and 18.8 (SD1⁄47.7) thereafter (p<0.001), with no increase in RSV seen with the 2008 safety communication. The mean number of web pages on Google containing 00transvaginal mesh00 between 2006-2010 was 2,484 (SD1⁄41,388) vs. 38,680 (SD1⁄412,859) between 2011-2015 (p<0.001); the largest increase in search terms was seen between 2010 (4,390 webpages) to 2011 (25,500 webpages), reflecting the effect of the 2011 update. CONCLUSIONS: The FDA communication regarding transvaginal mesh for POP in 2011 was associated with significant increases in both Google search activity and total number of webpages about transvaginal mesh. This suggests the rise in lawsuits and decreased use of transvaginal mesh for POP may be partially driven by increased patient awareness of complications.

MP10-18 GOOGLE TRENDS©: A MEASURE OF THE SOCIETAL IMPACT OF THE FDA TRANSVAGINAL MESH SAFETY COMMUNICATIONS

You have accessJournal of UrologyUrodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Pelvic Prolapse1 Apr 2016MP10-18 GOOGLE TRENDS©: A MEASURE OF THE SOCIETAL IMPACT OF THE FDA TRANSVAGINAL MESH SAFETY COMMUNICATIONS Juzar Jamnagerwalla, Brent Medoff, Karyn S. Eilber, and Jennifer T. Anger Juzar JamnagerwallaJuzar Jamnagerwalla More articles by this author , Brent MedoffBrent Medoff More articles by this author , Karyn S. EilberKaryn S. Eilber More articles by this author , and Jennifer T. AngerJennifer T. Anger More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.2348AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The efficacy of transvaginal mesh for anterior colporrhaphy is well established (Nguyen 2008); however, complications related to use of transvaginal mesh led to the release of FDA safety communications in 2008 and 2011. This led to a significant decrease in the use of transvaginal mesh for pelvic organ prolapse (POP) since 2011 (Clemens 2013). We hypothesized that the decrease in transvaginal mesh use was partly driven by increased patient awareness of complications. We tested this using Google Trends©, a public tool that provides data on temporal patterns of search terms and correlated this data with the timing of the FDA communications. METHODS Weekly relative search volume (RSV) was obtained from Google Trends© using the search term ″transvaginal mesh″, with higher RSV indicating an increase in search volume. These were divided into three groups: 2005 to July 13th 2011 (the date of the second FDA communication), a six-month period following the update, and thereafter until June 6th 2015. The distribution of the weekly RSV over the three periods was tested using one-way analysis of variance. We also tested the difference between total number of web pages containing ″transvaginal mesh″ (reported annually by Google) between 2006-2010 versus 2011-2015 using a paired t-test. RESULTS The mean RSV prior to the 2011 FDA communication was 0.73 [standard deviation (SD)=6.6], compared to 29.9 (SD=17.0) in the six months after the update and 18.8 (SD=7.7) thereafter (p<0.001), with no increase in RSV seen with the 2008 safety communication. The mean number of web pages on Google containing ″transvaginal mesh″ between 2006-2010 was 2,484 (SD=1,388) vs. 38,680 (SD=12,859) between 2011-2015 (p<0.001); the largest increase in search terms was seen between 2010 (4,390 webpages) to 2011 (25,500 webpages), reflecting the effect of the 2011 update. CONCLUSIONS The FDA communication regarding transvaginal mesh for POP in 2011 was associated with significant increases in both Google search activity and total number of webpages about transvaginal mesh. This suggests the rise in lawsuits and decreased use of transvaginal mesh for POP may be partially driven by increased patient awareness of complications. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e109 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Juzar Jamnagerwalla More articles by this author Brent Medoff More articles by this author Karyn S. Eilber More articles by this author Jennifer T. Anger More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Attitudes toward transvaginal mesh among patients in a urogynecology practice.

There has been increasing media attention regarding transvaginal mesh (TVM). We hypothesized that new urogynecology patients have limited knowledge and negative opinions of TVM. An anonymous survey was distributed to all new patients presenting to the Mt Auburn Hospital urogynecology practice from 1 November 2012 to 31 January 2013. A total of 146 patients completed the questionnaire. The survey was designed to elicit information on participants' knowledge and opinions about TVM and knowledge about recent FDA safety communications. All statistical tests were two-sided, and P values <0.05 were considered statistically significant. Analyses were restricted to the 77 women who had either heard of TVM or were unsure if they had heard of TVM. A minority (32.5 %) of these women correctly defined TVM, and 33.8 % had a negative impression of TVM. Respondents obtained their information on TVM from the media (48.1 %), the Internet (24.7 %), family or friends (22.1 %), and health care providers (18.2 %). The majority (71.4 %) agreed that they needed more information about TVM before making any decisions about using it to treat their condition. Nearly one quarter of respondents (23.4 %) agreed that they would not want their doctor to use TVM on them for any reason. When asked about recent FDA communications, 27.3 % of patients correctly responded that the FDA had released a safety communication regarding TVM. The majority of participants had limited knowledge of TVM; however, only a minority had negative opinions. Given our findings, it is important that providers spend more time during the consent process explaining TVM and its risks and benefits as a treatment option.

Increased Risk of Cardiovascular Events Associated with TKI Treatment in Chronic Phase Chronic Myeloid Leukemia. Data from Swedish Population-Based Registries

Introduction: The introduction of continuous tyrosine kinase inhibitor (TKI) treatment has dramatically improved progression-free survival for chronic phase chronic myeloid leukaemia (CML) patients. This success, however, has put the issue of long-term drug toxicity and safety into focus. Recent data from clinical studies have indicated an increased risk of cardiovascular events (CVE), including peripheral arterial occlusive disease, in CML patients receiving treatment with the TKIs nilotinib or ponatinib, as compared to imatinib (Giles et al, Leukemia 2013; Kim et al, Leukemia 2013; Cortes et al, New England Journal of Medicine 2013; FDA communication 2013).This study used data retrieved from Swedish population-based registries to estimate the frequency of CVE in CML patients, particularly those treated with imatinib and the 2nd generation TKIs nilotinib and dasatinib.Methods: We identified all incident cases between 2002 and 2012 in the Nationwide Swedish CML register. All patients who were in blast crisis or accelerated phase at time of diagnosis were excluded. All patients were followed untill death, emigration or 31st December 2012. For all CML patients a comparison cohort was established, matched to be of the same age and sex as the CML cohort, with 5 control subjects per CML patient. By means of record linkage with the nationwide Swedish patient register both cohorts were followed for the occurrence of adverse cardiovascular outcomes. Two sets of relative risks (expressed as incidence rate ratios; IRRs) of cardiovascular and venous thromboembolic disease were computed. In a first step CML patients were compared to the control population. In a second step, restricted to CML patients ever treated with TKIs, CML patients on different TKI treatments were compared. Patients could be treated with several TKIs during their follow-up, and events would only be attributable to the TKI used during the time period. Both analyses were adjusted for age, sex and calendar period. The second analysis was also adjusted for Sokal risk score.Results: A total of 896 CML patients were included and followed during a median of 4.2 years (Table I). The main outcome data are presented in Table II. A total of 23 venous thrombotic events (VTE) and 60 arterial thrombotic events were detected in the CML patient cohort during follow-up. Compared with the general population, this corresponded to significantly increased risks. In particular, deep venous thrombosis and “other arterial thromboses” were more common among CML patients (IRR 2.41 95% CI 1.29-4.52 and IRR 3.50 95% CI 1.36-9.04, respectively). Assessing risks associated with particular TKIs, we noted that treatment with any of the 2nd generation TKIs nilotinib or dasatinib, as compared to imatinib, was associated with a significantly increased occurrence of myocardial infarction (IRR 2.98 95% CI 1.05-8.49 and IRR 2.89 95% CI 1.20-7.00, respectively). Notably, there were no differences in the occurrence of CVE between the different patient groups before CML diagnosis.Conclusion: These data, derived from a large population-based Swedish cohort, provide evidence of an increased risk of both venous and arterial thrombotic events among CML patients and that patients on 2nd generation TKIs, as compared to imatinib, may be at increased risk of myocardial infarction. Further analyses will assess whether these differences may reflect patient selection and characterstics, rather than drug-related factors. Meanwhile, risk factors for CVE should be observed and considered in the TKI treatment of CML. [Display omitted] [Display omitted] * Footnote: the number of events may not add up because of occurrence of more than one type of vascular event in one subject. The number of events in the analysis within the CML cohort is lower than in the comparison with the general population because of exclusion of patients who were never treated with TKIs in the former analysis. DisclosuresBjörkholm:Novartis: Research Funding; Shire: Research Funding; Merck: Research Funding; Amgen: Honoraria, Research Funding; Pfizer: Research Funding; Bristol-Myers Squibb: Honoraria; Celgene: Honoraria; Akinon: Honoraria; Nordic Nanovector: Honoraria. Själander:Novartis: Honoraria. Richter:Ariad: Honoraria; Bristol-Myers Squibb: Honoraria; Novartis: Honoraria.

MP11-18 THE MEDICOLEGAL AND ECONOMIC IMPLICATIONS REGARDING THE USE OF TRANSVAGINAL MESH

You have accessJournal of UrologyGeneral & Epidemiological Trends & Socioeconomics: Practice Patterns, Cost Effectiveness II1 Apr 2014MP11-18 THE MEDICOLEGAL AND ECONOMIC IMPLICATIONS REGARDING THE USE OF TRANSVAGINAL MESH Marc Colaco, Austin Hester, Jason Sandberg, Jayadev Mettu, and Gopal Badlani Marc ColacoMarc Colaco More articles by this author , Austin HesterAustin Hester More articles by this author , Jason SandbergJason Sandberg More articles by this author , Jayadev MettuJayadev Mettu More articles by this author , and Gopal BadlaniGopal Badlani More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2014.02.433AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Although the use of transvaginal mesh placement has long been considered an option for the treatment of pelvic organ prolapse (POP), recent developments have brought this practice under controversy. Several studies have questioned the efficacy and safety of mesh usage, and the FDA has made multiple communications regarding the potential complications of mesh usage. While the implications for clinical practice are still hotly debated, these developments also have medicolegal and economic implications. Thus, the purpose of this study is to analyze the product liability litigation rate for two large mesh manufactures and to correlate these findings to FDA communications as well as other possibly related factors. METHODS Retrospective analysis was performed using legal case listings from the New Jersey judiciary Multicounty Litigation Center regarding mass tort for all pelvic mesh related cases filed prior to August 2013. This database was chosen as both Bard, Inc. and Ethicon Endo-Surgery, Inc. are based in New Jersey and thus New Jersey is the jurisdiction for these mass torts. Data was then compared to FDA communication releases and any landmark legal findings to determine correlation. Statistics were analyzed via parametric methods using Statsplus® software. RESULTS A total of 4385 Ethicon cases and 811 Bard cases were identified in this review. Rates of case filing did not significantly correlate to either FDA communication. Significant increases in filing were seen, however, in correlation with major verdicts decided in plaintiffs’ favors: mean number of cases filed within 3 months of either landmark court case was significantly higher than at all other times during this period (273 versus 67, p<0.01). CONCLUSIONS Device related lawsuits are an unfortunate reality of modern medicine, and awareness of liability is vital to the medical practice. Our results show that in regards to pelvic mesh related lawsuits case filings are more related to court decisions than to FDA communications. These findings may reflect the impact of financial incentives within the medicolegal arena, and demonstrate the need for physicians to keep abreast of current and ongoing legal precedence. © 2014FiguresReferencesRelatedDetails Volume 191Issue 4SApril 2014Page: e102-e103 Advertisement Copyright & Permissions© 2014MetricsAuthor Information Marc Colaco More articles by this author Austin Hester More articles by this author Jason Sandberg More articles by this author Jayadev Mettu More articles by this author Gopal Badlani More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Smokers' and Nonsmokers' Beliefs About Harmful Tobacco Constituents: Implications for FDA Communication Efforts

Smokers' and Nonsmokers' Beliefs About Harmful Tobacco Constituents: Implications for FDA Communication Efforts

Time series analyses of the effect of FDA communications on use of prescription weight loss medications

To determine the impact of FDA safety communications regarding the weight loss medications sibutramine and orlistat. The 2008 to 2011 pharmacy claims data from CVS Caremark were used to determine the effect of the relevant FDA warnings on (1) use of sibutramine and orlistat, (2) their rates of discontinuation, and (3) substitution to an alternate weight loss medication in the 3-month period following discontinuation. The use of sibutramine, orlistat, or phentermine declined from 45 users per 100,000 Caremark enrollees in May 2008 to 24 users per 100,000 enrollees in December 2010. In the time series analyses of overall use of medications, a very small decline in the trend of use of sibutramine after the FDA communication (0.000002% per month decline after the communication; P < 0.001) was found. However, rates of discontinuation of sibutramine and orlistat were similar before and after relevant FDA communications (all P values >0.1 for both level and trend changes post-warning). Patients discontinuing sibutramine post-communication increased use of phentermine at a rate of 0.004% per month after discontinuation (P = 0.01). From 2008 to 2010, use of prescription weight loss medications was low and declined over time. FDA communications regarding the safety of these medications had limited effect on use.

2150 PUBLIC PERCEPTION OF VAGINAL MESH AND THE MEDIA

You have accessJournal of UrologyUrodynamics/Incontinence/Female Urology: Pelvic Prolapse1 Apr 20132150 PUBLIC PERCEPTION OF VAGINAL MESH AND THE MEDIA Jennifer Chamberlain, Taylor Vaughn, J.Christian Winters, Eric S. Rovner, Melissa R. Kaufman, and Michelle Koski Jennifer ChamberlainJennifer Chamberlain New Orleans, LA More articles by this author , Taylor VaughnTaylor Vaughn Charleston, SC More articles by this author , J.Christian WintersJ.Christian Winters New Orleans, LA More articles by this author , Eric S. RovnerEric S. Rovner Charleston, SC More articles by this author , Melissa R. KaufmanMelissa R. Kaufman Nashville, TN More articles by this author , and Michelle KoskiMichelle Koski Charleston, SC More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2013.02.2059AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Since the 2011 FDA communication on transvaginal mesh (TVM), there has been a rapid increase in lawsuit advertisements in various media directly marketed to patients. We have encountered patients with heightened concerns citing these ads. Through a questionnaire-based study we hoped to assess the penetrance of ads into our patient population and to assess whether exposure to these ads affects patient opinion. METHODS A 17 item multiple choice survey was designed and beginning 8/2012, was given to female patients in urology and urogynecology clinics at two academic institutions after IRB approval. New patients with pelvic organ prolapse (POP) or stress incontinence (SUI) and patients who had undergone prior surgery at our institutions were excluded. We continue to accrue patients. RESULTS 78 questionnaires were completed. 53 (66.7%) of the patients had heard of TVM and of these, 33 (62%) cited such ads as the initial source of information. Regarding opinion of TVM, 1.9% chose “it is a safe product,” 7.5% “safety depends on factors related to patient,” 1.9% “not a safe product,” and 77.4% “I don't know.” 5.7% chose 2 selections and 3.8% patients chose “safety depends on the doctor”. Of those aware of TVM, 9 would consider mesh if they needed surgery for POP, 11 “no,” and 30 “maybe.” Of the “no” or “maybe” respondents- if a doctor told them they would benefit from mesh, 30.2% would change their mind, 9.4% would not, and 39.6% might. Only 11.3% indicated knowing the difference in use of TVM for POP vs. SUI. 15.1% were aware of the FDA safety communication. When asked what was the strongest influence on their opinion of TVM, responses were: advertisement, newspaper, or internet (32.1%), medical professional (26.4%), and “not sure” (28.3%). CONCLUSIONS Advertisements of TVM lawsuits have a high penetrance into our patient population. Few patients knew of the FDA communication or the difference in indication for TVM between POP and SUI. Despite this, patients indicated that they would still consider TVM, especially if advised by a physician. We must be aware of the effect of these ads on patient opinion and provide effective, unbiased, and scientifically accurate counseling of risks and benefits. © 2013 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 189Issue 4SApril 2013Page: e880-e881 Peer Review Report Advertisement Copyright & Permissions© 2013 by American Urological Association Education and Research, Inc.MetricsAuthor Information Jennifer Chamberlain New Orleans, LA More articles by this author Taylor Vaughn Charleston, SC More articles by this author J.Christian Winters New Orleans, LA More articles by this author Eric S. Rovner Charleston, SC More articles by this author Melissa R. Kaufman Nashville, TN More articles by this author Michelle Koski Charleston, SC More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Injector device manufacturer dismissed from pharmacy immunization case

Pharmacists are now able to administer immunizations in all states. This new role brings with it the potential for exposure to liability if harm is caused to a patient by a pharmacist-administered immunization. Fortunately, actual litigation against pharmacists has been very limited. The United States District Court for the Northern District of Ohio recently dismissed a case against the manufacturer of an injector device alleging harm caused to a patient by a pharmacy immunization. The ruling in the case raises issues of interest to pharmacists who administer immunizations to patients, although the pharmacy was not a party to the lawsuit. On October 11, 2011, a patient went to a pharmacy to obtain an influenza vaccination. The patient was administered a needle-free injection in his upper arm without being asked whether he would prefer that the immunization be administered using a needle. The patient asserted that he experienced swelling, redness, and soreness at the site of the injection and was surprised to feel pain and see blood at the injection site, because “he was told the injection device was needle-less.” The patient referred to a communication from FDA of October 21, 2011, sent to health professionals who administer influenza vaccine. The communication advised health professionals not to use injector devices to administer influenza vaccines and recommended that all vaccines, including influenza, be administered in accordance with their labeling. The communication noted the following:■“Currently, there is only one vaccine, measles, mumps and rubella (MMR), that is approved for administration by jet injector.■“FDA has no data to support the safety or effectiveness of other vaccines delivered by jet injector.■“At this time, there are no vaccines for the prevention of influenza disease that are approved by FDA for administration by jet injector.” The patient contended that the manufacturer should be held liable for damages caused to him by the needlefree injection device because the device was marketed to health professionals for the administration of influenza vaccine, although it was not approved by FDA for this purpose. The court noted that the patient’s lawsuit was based primarily on the FDA communication and the patient’s conclusion from the communication that the manufacturer had failed to comply with requirements of the federal Food, Drug, and Cosmetic Act (FDCA). The court concluded, however, that FDCA does not provide a private right of action for violation of its provisions. Only FDA has the authority to enforce FDCA if it finds that a manufacturer has committed a violation. A private person cannot sue a manufacturer to enforce provisions of FDCA. The patient also claimed that a violation of state consumer protection laws could serve as the basis of manufacturer liability. The court disagreed. For there to be liability under these state laws, there must be evidence that the patient relied on representations made by the manufacturer. The patient did not allege that he saw, or was even aware of, any alleged misrepresentations regarding the needle-free injection device before or during the administration of his influenza vaccine. Rather, the lawsuit made it clear that the patient went to a pharmacy to obtain an influenza vaccine and that his attorney later discovered advertisements by the pharmacy indicating that it would provide “needlefree” injections. The lawsuit referenced statements made on the manufacturer’s website, but it was clear that the patient was unaware of these statements at the time of the immunization, so they could not possibly have been relied on by the patient. The case against the manufacturer was dismissed. Perhaps the most interesting aspect of this case is the patient’s expression of surprise at harm caused by what the patient apparently perceived to be a harmless device. Informed consent has become a cornerstone of medical practice, and as pharmacists expand their practice sphere into areas formerly occupied exclusively by physicians, they will need to adopt the risk management practices of physicians. One of the key purposes of informed consent is to prevent surprise by patients if a risk materializes following the provision of care. In this case, there was no mention of a signed informed consent document describing the nature of the influenza vaccine, the manner in which it would be administered, or the risks of the vaccine and its administration. Effective risk management, and respectful patient care, require adherence to the principles of informed consent when vaccines are administered to patients. Based on: Reeves vPharmajet, Inc., 2012 U.S.Dist. LEXIS 14957 (February 3, 2012).