Shorter Review Times Research Articles

The multifaceted factors affecting the publication times of pediatric ophthalmology and strabismus articles: what has changed in two decades

AbstractExpeditious publication is an important factor when considering publishing ophthalmic research. We investigated the factors associated with shorter publication times in pediatric ophthalmology and strabismus (POS). We analyzed 2487 POS articles from 8 ophthalmology journals publishing POS articles. Time from submission to acceptance, from acceptance to publication, and from submission to publication were calculated for each article. We compared trends over time of factors affecting the publication times from 2002 to 2007 and those from 2014 to 2018. Median peer review durations were 156 days from submission to acceptance; 79 days from acceptance to publication, and 244 days from submission to publication. The American Journal of Ophthalmology, JAMA Ophthalmology, and Strabismus had the shortest submission to publication time. Authors from Africa, East Europe, Central and South America received the fastest processing time in all time categories, although most authors were based in North America and UK. All-time intervals decreased annually, significantly more during the first decade. In the study's second period, more co-authors and affiliated departments correlated with shorter review times. Manuscripts in higher Impact Factor (IF) journals had faster publication times in the first decade. Female senior authors faced longer submission-to-acceptance times in the first decade. This gender gap disappeared in the second period. A general improvement occurred with most journals, specifically those journals with a higher number of co-authors and affiliated departments, indicating an efficient collaborative authorship. Low-income regions benefited from comparatively shorter time intervals. The gender gap in senior authorship diminished over time.

Asociación de las características del ensayo con la publicación simultánea y su impacto en citas y menciones: un estudio transversal

Introduction and objectivesRandomized trials are often presented at medical conferences and published simultaneously or later. Predictors of simultaneous publication and its consequences are undetermined. Our aim was to characterize the practice of simultaneous publication, identify its predictors, and evaluate its impact. MethodsIn this cross-sectional study, we included randomized trials presented at late-breaking science sessions of major cardiovascular conferences from 2015 to 2021. The association of trial characteristics with the timing of publication was analyzed. The impact of simultaneous vs nonsimultaneous publication was investigated on the number of 1-year citations and 1-month mentions, and the total citations and mentions at the longest observation follow-up. ResultsOf 478 trials included in the analysis, 48.7% were published simultaneously. Simultaneous publications were more likely to be presented in the main conference room (OR, 6.09; 95%CI, 1.34-36.92; P=.029) and were characterized by a shorter review time (OR, 0.95; 95%CI, 0.91-0.96; P<.001). Simultaneous publications were associated with higher 1-year citations (R2, 43.81; 95%CI, 23.89-63.73; P<.001), 1-month mentions (R2, 132.32; 95%CI, 85.42-179.22; P<.001) and total citations (R2, 222.89; 95%CI, 127.98-317.80; P<.001). ConclusionsRandomized trials presented in the main conference room and with shorter review time were more likely to be published simultaneously. Simultaneous publications were associated with more citations and mentions than nonsimultaneous publications.

Association of trial characteristics with simultaneous publication and its impact on citations and mentions: a cross-sectional study

Introduction and objectivesRandomized trials are often presented at medical conferences and published simultaneously or later. Predictors of simultaneous publication and its consequences are undetermined. Our aim was to characterize the practice of simultaneous publication, identify its predictors, and evaluate its impact. MethodsIn this cross-sectional study, we included randomized trials presented at late-breaking science sessions of major cardiovascular conferences from 2015 to 2021. The association of trial characteristics with the timing of publication was analyzed. The impact of simultaneous vs nonsimultaneous publication was investigated on the number of 1-year citations and 1-month mentions, and the total citations and mentions at the longest observation follow-up. ResultsOf 478 trials included in the analysis, 48.7% were published simultaneously. Simultaneous publications were more likely to be presented in the main conference room (OR, 6.09; 95%CI, 1.34-36.92; P=.029) and were characterized by a shorter review time (OR, 0.95; 95%CI, 0.91-0.96; P<.001). Simultaneous publications were associated with higher 1-year citations (R2, 43.81; 95%CI, 23.89-63.73; P<.001), 1-month mentions (R2, 132.32; 95%CI, 85.42-179.22; P<.001) and total citations (R2, 222.89; 95%CI, 127.98-317.80; P<.001). ConclusionsRandomized trials presented in the main conference room and with shorter review time were more likely to be published simultaneously. Simultaneous publications were associated with more citations and mentions than nonsimultaneous publications.

Cancer Therapy Approval Timings, Review Speed, and Publication of Pivotal Registration Trials in the US and Europe, 2010-2019

Ensuring patients have access to safe and efficacious medicines in a timely manner is an essential goal for regulatory agencies, one which has particular importance in oncology because of the substantial unmet need for new therapies. The 2 largest regulatory agencies, the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA), have pivotal global roles, and their recommendations and approvals are frequently followed by other national regulators. To compare market authorization dates for new oncology therapies approved in the US and Europe over the past decade and to examine and contrast the regulatory activities of the FDA and EMA in the approval of new cancer medicines. This cross-sectional study reviewed the FDA and EMA regulatory databases to identify new oncology therapies approved in both the US and Europe from 2010 to 2019, and characterization of the timings of regulatory activities. Statistical analysis was performed from January to April 2022. Regulatory approval date, review time, submission of market authorization application, accelerated approval or conditional marketing authorization status and proportion of approvals prior to peer-reviewed publication of pivotal trial results. In total, 89 new concomitant oncology therapies were approved in the US and Europe from 2010 to 2019. The FDA approved 85 oncology therapies (95%) before European authorization and 4 therapies (5%) after. The median (IQR) delay in market authorization for new oncology therapies in Europe was 241 (150-370) days compared with the US. The median (IQR) review time was 200 (155-277) days for the FDA and 426 (358-480) days for the EMA. Sixty-four new licensing applications (72%) were submitted to the FDA first, compared with 21 (23%) to the EMA. Thirty-five oncology therapies (39%) were approved by the FDA prior to pivotal study publication, whereas only 8 (9%) by the EMA. In this cross-sectional study, new oncology therapies were approved earlier in the US than Europe. The FDA received licensing applications sooner and had shorter review times. However, more therapies were approved prior to licensing study publication, leaving uncertainty for practitioners regarding clinical utility and safety of newly approved therapies.

The impact of regulatory review time on incremental and radical innovation: evidence from the high-risk medical device market

We theoretically and empirically study the effect of variation in regulatory review time on firms’ choices between radical and incremental innovations. We differentiate between entry into new segments (the extensive margin) and increasing the number of innovations in a given sector (the intensive margin). Our theoretical investigation indicates additional entry into medical device segments as a result of shorter application review times. It also predicts firm-level substitution effect, suggesting firms shift their R&D to innovation applications with relatively shorter review times. To test the theoretical predictions, we utilize a unique data set from the U.S. Food and Drug Administration that contains all product market approvals in the high-risk medical device market for the 1978–2007 period. The empirical results generally support our theoretical predictions. However, the results also show that firms are more responsive to changes in the review time for incremental applications compared to radical ones.

Multi-project environmental impact assessment: insights from offshore oil and gas development in Brazil

ABSTRACTDespite being adopted worldwide, environmental impact assessment (EIA) is under pressure in many countries, while perceived (rightly or wrongly) as an ineffective and inefficient process. Strategic environmental assessment (SEA) is thought to help address some of EIA’s shortcomings, but it is absent in many jurisdictions and sectors. In this paper, we argue that multi-project EIA can, in some contexts, simultaneously deliver greater effectiveness and process streamlining. To illustrate our claim, we present a case study from offshore petroleum production in Brazil, where the development of the pre-salt giant reserves is being licensed through a multi-project EIA approach, in a non-SEA planning environment. The analysis provides interesting insights on the strengths and challenges of that strategy, focusing on five aspects of practice: cumulative impacts, efficiency, approach to authorizations, follow-up and political issues. Proper scoping was found to be essential to consistent EIA processes and shorter review times. Finally, we suggest that multi-project EIA approach should be revisited by practitioners and regulators to identify opportunities for deployment, especially in jurisdictions where strategic assessments are not in place.

Performance of Spectrogram-Based Seizure Identification of Adult EEGs by Critical Care Nurses and Neurophysiologists.

Continuous EEG screening using spectrograms or compressed spectral arrays (CSAs) by neurophysiologists has shorter review times with minimal loss of sensitivity for seizure detection when compared with visual analysis of raw EEG. Limited data are available on the performance characteristics of CSA-based seizure detection by neurocritical care nurses. This is a prospective cross-sectional study that was conducted in two academic neurocritical care units and involved 33 neurointensive care unit nurses and four neurophysiologists. All nurses underwent a brief training session before testing. Forty two-hour CSA segments of continuous EEG were reviewed and rated for the presence of seizures. Two experienced clinical neurophysiologists masked to the CSA data performed conventional visual analysis of the raw EEG and served as the gold standard. The overall accuracy was 55.7% among nurses and 67.5% among neurophysiologists. Nurse seizure detection sensitivity was 73.8%, and the false-positive rate was 1-per-3.2 hours. Sensitivity and false-alarm rate for the neurophysiologists was 66.3% and 1-per-6.4 hours, respectively. Interrater agreement for seizure screening was fair for nurses (Gwet AC1 statistic: 43.4%) and neurophysiologists (AC1: 46.3%). Training nurses to perform seizure screening utilizing continuous EEG CSA displays is feasible and associated with moderate sensitivity. Nurses and neurophysiologists had comparable sensitivities, but nurses had a higher false-positive rate. Further work is needed to improve sensitivity and reduce false-alarm rates.

Advantages of using an abbreviated dossier for drug master file applications in Taiwan

In Taiwan, the quality of active pharmaceutical ingredients is recorded in a drug master file (DMF), the applications for which can be submitted in two dossier types, either full (complete technical information) or abbreviated (partially complete technical information with an approved document issued by developed countries). However, the advantages of the abbreviated approach remain unknown. This study compared full and abbreviated dossier profiles and reviewed their outcomes in acceptance rates and deficiencies leading to rejection. Data were collected from new submissions of both dossier types that were completed in 2014 by the Center for Drug Evaluation, Taiwan. The results revealed that the abbreviated applications took shorter review time and had a higher acceptance rate. Among the eligible types of document for abbreviated applications, Certification of Suitability to the Monographs of the European Pharmacopeia (CEP) was the most frequently used. For categorical deficiencies, both dossier types presented the deficiencies in similar sections leading to rejection, namely Manufacture (3.2.S.2), Control of drug substance (3.2.S.4), and Stability (3.2.S.7). In summary, CEP serves a favorable document for the abbreviated DMF application in which it shortens the review time, increases the acceptance rate, and its deficiencies are similar to those of the full DMF application.

Clinical trial designs to obtain marketing authorization of drugs for haematological malignancy in Japan, the EU and the US.

Differences in regulatory actions between Japan, the European Union (EU) and the United States (US) regarding the approval date and primary endpoints of pivotal trials have never been analysed comprehensively. This study aimed to examine such differences in haematological malignancy indications not only in applications for new molecular entity agents but also in supplemental applications for additional indications. A total of 101 haematological malignancy indications were examined for 58 drugs. Only 30 indications were approved by the regulatory agencies of all three regions with 25, 9 and 67 indications being first approved in Japan, the EU and the US, respectively. Regarding the 18 indications approved only in the US, 13 were approved based on results of single-arm trials. The approval of all nine indications approved first in the EU was based on results of comparative trials. The primary endpoints were different between the EU and the US in 4 of 49 indications approved by both regulatory agencies, all of which were approved earlier in the US than in the EU. This analysis shows that the US Food and Drug Administration has taken the most active attitude to acceptance of surrogate endpoints in single-arm trials. Therefore, not only shorter review time but also this attitude may lead to earlier approval in US.

Endpoints of Clinical Trials for Marketing Authorization of Drugs for Hematologic Malignancy in Japan, the US and the EU

Background: Pharmaceuticals and Medical Devices Agency (PMDA) in Japan, the US Food and Drug Administration (FDA) in the US and the European Medicines Agency (EMA) in the EU review drug applications for market approval. It was shown that most new molecular entity (NME) agents were first approved in the US because the FDA has reviewed applications more quickly (N Engl J Med. 2012; 366: 2284-93). However, differences in regulatory actions among Japan, the US and the EU in terms of relationship between the approval date and primary endpoints of pivotal trials in marketing applications including supplemental applications for additional indications have never been analyzed comprehensively. Methods: 93 indications of 55 hematologic anticancer drugs approved in Japan, the US or the EU (only central marketing authorization by the European Commission) between August 2000 and June 2014 were examined in this research. Information concerning regulatory decisions made by PMDA, the FDA and the EMA was obtained from publicly accessible data only such as PMDA’s review reports, the PMDA website, the FDA’s review reports, the Drugs@FDA website, the European public assessment reports published by the EMA’s Committee for Medicinal Products for Human Use (CHMP) and the EMA website. Results: 24, 60, and 9 indications were first approved in Japan, the US, and the EU, respectively. 2 NME agents were first approved in Japan and the EU each; mogamulizumab for relapsed CCR4-positive adult T-cell leukemia/lymphoma as well as relapsed CCR4-positive peripheral T-cell lymphoma/cutaneous T-cell lymphoma and tamibarotene for relapsed acute promyelocytic leukemia in Japan and pixantrone dimaleate for relapsed aggressive non-Hodgkin B-cell lymphoma and histamine dihydrochloride for acute myeloid leukemia in the EU. 17 indications were approved only in the US and 13 of these were approved based on response rate in single-arm trials. The other 4 indications were approved based on results of comparative trials. Of the 13 indications approved based on single-arm trials, 8 indications were approved through the accelerated approval scheme in the US. 5 indications (pixantrone dimaleate, histamine dihydrochloride, temsirolimus for relapsed mantle cell lymphoma, rituximab as maintenance therapy for relapsed follicular lymphoma and decitabine for acute myeloid leukemia) were approved only in the EU and 4 other indications (ibritumomab tiuxetan as consolidation therapy for follicular lymphoma and rituximab for diffuse large B-cell lymphoma, newly diagnosed chronic lymphocytic leukemia, and relapsed chronic lymphocytic leukemia) were approved the earliest in the EU. All these 9 indications were approved based on results of comparative trials. Of these 9 indications, only pixantrone dimaleate was approved through the conditional approval scheme and only histamine dihydrochloride was approved through the approval under exceptional circumstances scheme. Although 23 indications were approved only in Japan, most of them were additional indications of old drugs and not based on results of comparative trials. Primary endpoints were different between the US and the EU in 3 of 41 indications approved in both the US and the EU. All these 3 indications were approved earlier in the US and response rate or time to progression (TTP) in the US instead of progression-free survival (PFS) or overall survival (OS) in the EU was adopted as the primary endpoints as follows; thalidomide for newly diagnosed multiple myeloma (TTP in the US and OS in the EU), pomalidomide for relapsed multiple myeloma (overall response rate in the US and PFS in the EU), and azacitidine for myelodysplastic syndrome (complete remission rate in the US and OS in the EU). Conclusions: The conditional approval scheme or the approval under exceptional circumstances scheme in the EU and the accelerated approval scheme in the US are available, while there are no similar schemes for oncologic drugs in Japan. However, this analysis suggests that the FDA has taken a more active attitude to acceptance of surrogate endpoints. Therefore, not only shorter review time but also this attitude may lead to earlier marketing authorization of drugs for hematologic malignancy in the US. Disclosures Off Label Use: I will discuss off-label drug use in the US which has been approved in the EU or Japan..

Therapeutic Ratings and End‐of‐Phase II Conferences: Initiatives to Accelerate the Availability of Important New Drugs Kenneth I. Kaitin, PhD

To facilitate the availability of important new therapeutic agents, the Food and Drug Administration (FDA) in the mid‐1970s began assigning therapeutic ratings to investigational new drugs and holding end‐of‐phase II conferences with drug sponsors. To determine whether these initiatives are associated with faster approvals, we examined new drug application (NDA) review times of new chemical entities (NCEs) approved during the 12‐year period 1978 through 1989. Mean NDA review time for 1A drugs (22.5 months) was 22% shorter than that for 1B drugs (28.7 months), which in turn was 25% shorter than that for 1C drugs (38.4 months). For drugs approved during the recent 4‐year period 1986 through 1989, however, the gap between 1A and 1C review times has narrowed considerably from 19 to 9 months. When drugs were grouped by FDA reviewing division, 1A drugs had the shortest mean review time in each division except the Cardio‐Renal Division; in that division, 1B drugs had the shortest mean review time. Mean NDA review time for drugs that had end‐of‐phase II conferences (28.6 months) was 15% shorter than that for drugs without such conferences (33.7 months). These results suggest that NCEs that receive 1A or 1B ratings and are the subject of end‐of‐phase II conferences benefit by having shorter review times.