Clinical Evidence Supporting US Food and Drug Administration Clearance of Novel Therapeutic Devices via the De Novo Pathway Between 2011 and 2019.
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ABSTRACT:
SUBMITTER: Johnston JL
PROVIDER: S-EPMC7551221 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ImportanceMedical Device Safety Communications (MDSCs) are used by the US Food and Drug Administration (FDA) to convey important new safety information to patients and health care professionals. The sources of initial safety signals that trigger MDSCs have not been described previously.ObjectiveTo assess the sources of initial safety signals that trigger publication of MDSCs and the potential associations among MDSC data source, type of safety issue, and subsequent FDA action.Design, setting, and participantsIn this cross-sectional study, all MDSCs published on the FDA website between January 1, 2011, and December 31, 2019, were assessed. The MDSC characteristics, sources of initiating safety signals, regulatory approval or clearance pathways of the related medical devices, and subsequent FDA actions were collected from the FDA website.Main outcomes and measuresThe main outcome was the distribution of sources of initial safety signals that led to publication of MDSCs. Secondary aims included exploration of potential associations among safety signal sources (direct reporting vs other), type of safety issue (death vs other), and FDA action (withdrawal vs other).ResultsA total of 93 MDSCs were evaluated. Median time from device approval to MDSC posting was 10 years (interquartile range, 6-16 years). The most common data sources that triggered MDSCs were direct reports to the FDA through the Medical Device Reporting (MDR) program (44 of 93 [47%]) followed by regulator-initiated assessments (32 [34%]). Common safety issues included patient injury (25 [27%]), potential wrong diagnoses (19 [20%]), and death (18 [19%]). Frequent FDA action after MDSC posting included recommendation for increased vigilance and caution (47 [51%]), complete device withdrawal (12 [13%]), and warnings of specific lots or clinics (12 [13%]). There was a statistically significant correlation between direct reports of adverse events to the FDA through the MDR program and risk of death as a safety issue (14 of 44 [32%] for direct reporting vs 4 of 49 [8%] for any other data sources, P = .007).Conclusions and relevanceIn this cross-sectional study, the most common source of initial safety signals that triggered MDSCs was direct reports of real-world adverse events to the FDA through the MDR program. The delayed detection of postmarketing adverse events highlights the importance of proactive identification of emerging device-related safety issues.
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Project description:ObjectiveExposure to unhealthy food advertising is a known determinant of children's poor dietary behaviours. The purpose of this study was to quantify and characterize Canadian children's exposure to food advertising on broadcast television and examine trends over time.MethodsObjectively measured advertising exposure data for 19 food categories airing on 30 stations broadcast in Toronto were licenced for May 2011 and May 2019. Using ad ratings data, the average number of food advertisements viewed by children aged 2-11 years, overall, by food category and by type of television station (child-appealing, adolescent-appealing and generalist stations), was estimated per time period.ResultsIn May 2019, children viewed an average of 136 food advertisements on television, 20% fewer than in May 2011. More than half of advertisements viewed in May 2019 promoted unhealthy food categories such as fast food (43% of exposure), candy (6%), chocolate (6%) and regular soft drinks (5%) and only 17% of their total exposure occurred on child-appealing stations. Between May 2011 and May 2019, children's exposure increased the most, in absolute terms, for savory snack foods (+7.2 ad exposures/child), fast food (+5.4) and regular soft drinks (+5.3) with most of these increases occurring on generalist stations.ConclusionCanadian children are still exposed to advertisements promoting unhealthy food categories on television despite voluntary restrictions adopted by some food companies. Statutory restrictions should be adopted and designed such that children are effectively protected from unhealthy food advertising on both stations intended for general audiences and those appealing to younger audiences.
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Project description:ImportanceClinical trial evidence used to support drug approval is typically the only information on benefits and harms that patients and clinicians can use for decision-making when novel cancer therapies become available. Various evaluations have raised concern about the uncertainty surrounding these data, and a systematic investigation of the available information on treatment outcomes for cancer drugs approved by the US Food and Drug Administration (FDA) is warranted.ObjectiveTo describe the clinical trial data available on treatment outcomes at the time of FDA approval of all novel cancer drugs approved for the first time between 2000 and 2016.Design, setting, and participantsThis comparative effectiveness study analyzed randomized clinical trials and single-arm clinical trials of novel drugs approved for the first time to treat any type of cancer. Approval packages were obtained from drugs@FDA, a publicly available database containing information on drug and biologic products approved for human use in the US. Data from January 2000 to December 2016 were included in this study.Main outcomes and measuresRegulatory and clinical trial characteristics were described. For randomized clinical trials, summary treatment outcomes for overall survival, progression-free survival, and tumor response across all therapies were calculated, and median absolute survival increases were estimated. Tumor types and regulatory characteristics were assessed separately.ResultsBetween 2000 and 2016, 92 novel cancer drugs were approved by the FDA for 100 indications based on data from 127 clinical trials. The 127 clinical trials included a median of 191 participants (interquartile range [IQR], 106-448 participants). Overall, 65 clinical trials (51.2%) were randomized, and 95 clinical trials (74.8%) were open label. Of 100 indications, 44 indications underwent accelerated approval, 42 indications were for hematological cancers, and 58 indications were for solid tumors. Novel drugs had mean hazard ratios of 0.77 (95% CI, 0.73-0.81; I2 = 46%) for overall survival and 0.52 (95% CI, 0.47-0.57; I2 = 88%) for progression-free survival. The median tumor response, expressed as relative risk, was 2.37 (95% CI, 2.00-2.80; I2 = 91%). The median absolute survival benefit was 2.40 months (IQR, 1.25-3.89 months).Conclusions and relevanceIn this study, data available at the time of FDA drug approval indicated that novel cancer therapies were associated with substantial tumor responses but with prolonging median overall survival by only 2.40 months. Approval data from 17 years of clinical trials suggested that patients and clinicians typically had limited information available regarding the benefits of novel cancer treatments at market entry.
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