Person: Kesselheim, Aaron
Loading...
Email Address
AA Acceptance Date
Birth Date
Research Projects
Organizational Units
Job Title
Last Name
Kesselheim
First Name
Aaron
Name
Kesselheim, Aaron
29 results
Search Results
Now showing 1 - 10 of 29
Publication Comparison of Rates of Safety Issues and Reporting of Trial Outcomes for Medical Devices Approved in the European Union and United States: Cohort Study(BMJ, 2016-06-28) Hwang, Thomas; Sokolov, Elisaveta; Franklin, Jessica M; Kesselheim, AaronOBJECTIVE To evaluate safety alerts and recalls, publication of key trial outcomes, and subsequent US approval of high profile medical devices introduced in the European Union. DESIGN Cohort study. SETTING Novel cardiovascular, orthopedic, and neurologic devices approved in the EU through Conformite Europeenne marking between 2005 and 2010. DATA SOURCES Public and commercial databases searched up to January 2016 for press releases and announcements of approvals; public Food and Drug Administration and European regulatory authority databases for US approvals and safety alerts and recalls; and Medline, Embase, and Web of Science for peer reviewed publications. MAIN OUTCOME MEASURES We categorized the novelty of the devices in the study sample as a "major innovation" or an "other change," and extracted descriptive data about the devices and information on any safety alerts and withdrawals. Linear regression models examined factors associated with differential EU and US approvals. Cox proportional hazards regression models were used to evaluate factors associated with safety alerts and recalls and the publication of trial outcomes for devices categorized as major innovations. Models controlled for time, therapeutic category, regulatory pathway, size of sponsoring company, and indicator variables for devices approved first in the EU and devices approved only in the EU.RESULTS67% (206/309) of devices identified were approved in both the US and the EU, of which 63% (129/206) were approved first in the EU. The unadjusted rate of safety alerts and recalls for devices approved first in the EU was 27% (62/232) compared with 14% (11/77) for devices approved first in the US. The adjusted hazard ratio for safety alerts and recalls was 2.9 (95% confidence interval 1.4 to 6.2) for devices approved first in the EU. The results of pivotal trials were published for 49% (37/75) of devices categorized as major innovations, with an overall publication rate of 37% five years after approval. CONCLUSIONS Devices approved first in the EU are associated with an increased risk of post-marketing safety alerts and recalls. Poor trial publication rates mean that patients and clinicians need greater regulatory transparency to make informed decisions about treatment.Publication Infections following bispecific antibodies in myeloma: a systematic review and meta-analysis(American Society of Hematology, 2023-09-29) Reynolds, Gemma; Cliff, Edward; Mohyuddin, Ghulam Rehman; Popat, Rakesh; Midha, Shonali; Liet Hing, Melissa Ng; Harrison, Simon J.; Kesselheim, Aaron; Teh, Benjamin W.Bispecific antibodies, a novel immunotherapy with promising efficacy against multiple myeloma, form immune synapses between T-cell surface marker CD3 and malignant cell markers, including B-cell maturation antigen (BCMA), FcRH5, and G protein–coupled receptor GPRC5D. These bispecific antibodies so effectively deplete plasma cells (and to some extent T-cells) that patients are at increased risk of developing infections. A systematic review and meta-analysis of infections in published studies of patients with myeloma treated with bispecific antibodies was conducted to better characterize the infection risks. A literature search used MEDLINE, EMBASE, and Cochrane to identify relevant studies between inception and February 10, 2023, including major conference presentations. Phase 1b-3 clinical trials and observational studies were included. Sixteen clinical trials comprising 1666 patients were included. Median follow-up was 7.6 months and 38% of the cohort had penta-drug refractory disease. Pooled prevalence of all-grade infections was 56%, whereas the prevalence of grade ≥3 infections was 24%. Patients who were treated with BCMA-targeted bispecifics had significantly higher rates of grade ≥3 infections than non-BCMA bispecifics (25% vs 20%). Similarly, patients treated with bispecifics in combination with other agents had significantly higher rate of all-grade infection than those receiving monotherapy (71% vs 52%). In observational studies (n = 293), excluded from the primary analysis to ensure no overlap with patients in clinical trials, several infections classically associated with T-cell depletion were identified. This systematic review identifies BCMA-targeted bispecifics and bispecific combination therapy as having higher infection risk, requiring vigilant infection screening and prophylaxis strategies.Publication Postmarketing Trials and Pediatric Device Approvals(American Academy of Pediatrics (AAP), 2014) Hwang, Thomas; Kesselheim, Aaron; Bourgeois, FlorenceBACKGROUND: Medical devices can be useful in a variety of diseases, but few devices have been specifically approved for use in children. The 2007 Pediatric Medical Device Safety and Improvement Act was passed to stimulate pediatric device development. The current state of trial evidence underpinning the approval of pediatric devices remains poorly described. METHODS: We identified all high-risk (ie, class III) devices approved through the premarket approval or humanitarian device exemption pathways for therapeutic use in children between 2008 and 2011. We collected key information on clinical trial design (randomization, blinding, controls, and types of end points) as well as age distribution of trial participants. We also identified US Food and Drug Administration (FDA)–mandated postmarketing trials. RESULTS: Twenty-two devices were approved for use in children via the premarket approval pathway and 3 via the humanitarian device exemption pathway. Twenty-two (88%) qualified as pediatric despite minimum approval ages of ≥18 years (the FDA Center for Devices and Radiologic Health considers patients 18–21 years old as pediatric). Most devices were approved on the basis of nonrandomized (59%), open-label (68%) studies with surrogate effectiveness end points (86%). Overall, 21 (84%) devices were not studied in any patients <18 years of age. Postmarketing studies were mandated by the FDA for 19 (76%) devices, although only 3 (18%) required enrollment of pediatric patients. CONCLUSIONS: Most high-risk pediatric devices are approved on the basis of trials in patients ≥18 years old, with few pediatric patients exposed to the devices before market availability. Few postmarketing studies require additional study in pediatric patients.Publication Burden of Changes in Pill Appearance for Patients Receiving Generic Cardiovascular Medications After Myocardial Infarction(American College of Physicians, 2014) Kesselheim, Aaron; Bykov, Katsiaryna; Avorn, Jerome; Tong, Angela; Doherty, Michael Joseph; Choudhry, NiteeshBackground: Generic prescription drugs made by different manufacturers may vary in color or shape, and switching among these drug products may interrupt medication use. Objective: To determine whether nonpersistent use of generic drugs among patients with cardiovascular disease after myocardial infarction (MI) is associated with inconsistent appearance of their medications. Design: Cohort and nested case–control studies. Setting: Claims from a commercial health insurance database in the United States. Patients: Patients discharged after hospitalization for MI between 2006 and 2011 who initiated treatment with a generic β-blocker, angiotensin-converting enzyme inhibitor, angiotensin II–receptor blocker, or statin. Case patients discontinued their index medication for at least 1 month; control patients continued treatment. Control patients were matched to case patients on therapeutic class, number of dispensings before nonpersistence, sex, and age. Measurements: Rates of changes in pill color and shape during the year after MI were calculated. Next, 2 refills preceding nonpersistence were evaluated to determine whether pill color or shape had changed. Odds of discordance among case and control patients were compared using conditional logistic regression. Results: A total of 29% of patients (3286 of 11 513) had a change in pill shape or color during the study. Statins had the most changes in appearance, whereas β-blockers had the fewest. A total of 4573 episodes of nonpersistence was matched to 19 881 control episodes. The odds of nonpersistence in case patients increased by 34% after a change in pill color (adjusted odds ratio, 1.34 [95% CI, 1.12 to 1.59]) and 66% after a change in pill shape (adjusted odds ratio, 1.66 [CI, 1.43 to 1.94]). Limitation: Only 3 categories of drugs indicated after MI were evaluated, and clinical outcomes were not addressed. Conclusion: Variation in the appearance of generic pills is associated with nonpersistent use of these essential drugs after MI among patients with cardiovascular disease. Primary Funding Source: Agency for Healthcare Research and Quality and the Harvard Program in Therapeutic Science.Publication Postmarket Surveillance of Medical Devices: A Comparison of Strategies in the US, EU, Japan, and China(Public Library of Science, 2013) Kramer, Daniel; Tan, Yongtian T.; Sato, Chiaki; Kesselheim, AaronDaniel Kramer and colleagues compare strategies for postmarket surveillance of medical devices and discuss ways to improve these systems. Please see later in the article for the Editors' SummaryPublication Clinicians’ Contributions to the Development of Coronary Artery Stents: A Qualitative Study of Transformative Device Innovation(Public Library of Science, 2014) Kesselheim, Aaron; Xu, Shuai; Avorn, JeromeBackground: Medical device innovation remains poorly understood, and policymakers disagree over how to incentivize early development. We sought to elucidate the components of transformative health care innovation by conducting an in-depth case study of development of a key medical device: coronary artery stents. Methods and Findings: We conducted semi-structured interviews with the innovators whose work contributed to the development of coronary artery stents who we identified based on a review of the regulatory, patent, and medical literature. Semi-structured interviews with each participant covered the interviewee’s personal involvement in coronary artery stent development, the roles of institutions and other individuals in the development process, the interplay of funding and intellectual property in the interviewee’s contribution, and finally reflections on lessons arising from the experience. Transcripts were analyzed using standard coding techniques and the constant comparative method of qualitative data analysis. Conclusions: We found that the first coronary artery stents emerged from three teams: Julio Palmaz and Richard Schatz, Cesare Gianturco and Gary Roubin, and Ulrich Sigwart. First, these individual physician-inventors saw the need for coronary artery stents in their clinical practice. In response, they developed prototypes with the support of academic medical centers leading to early validation studies. Larger companies entered afterwards with engineering support. Patents became paramount once the technology diffused. The case of coronary stents suggests that innovation policy should focus on supporting early physician-inventors at academic centers.Publication Same Song, Different Audience: Pharmaceutical Promotion Targeting Non-Physician Health Care Providers(Public Library of Science, 2013) Yeh, James; Kesselheim, AaronPublication Rising Health Care Costs and Life-Cycle Management in the Pharmaceutical Market(Public Library of Science, 2013) Kesselheim, AaronAaron Kesselheim discusses Natalie Vernaz and colleagues' paper on the effects on health care costs of “evergreening” strategies pursued by drug manufacturers. Please see later in the article for the Editors' SummaryPublication Reputation and Precedent in the Bevacizumab Decision(New England Journal of Medicine (NEJM/MMS), 2011) Kesselheim, Aaron; Joffe, StevenPublication Regulatory Solutions to the Problem of High Generic Drug Costs(Oxford University Press, 2015) Luo, Jing; Sarpatwari, Ameet; Kesselheim, AaronRecent reports have highlighted dramatic price increases for several older generic drugs, including a number of essential products used to treat deadly infectious diseases. Although most of these medicines have been widely available at reasonable prices for decades, some manufacturers have seized on unique features of the pharmaceutical marketplace to seek substantial profits. In this Perspective, we examine limitations in current price regulation among public and private payors and consider several reforms that could address the problem of expensive generic drugs through improved competition.
- «
- 1 (current)
- 2
- 3
- »