Ética en investigación: desafíos durante la pandemia / Research ethics: challenges during the pandemic

Durante la pandemia de Covid-19 los hospitales pediatricos se vieron menos afectados, debido a la menor infección en niños, y sus recursos fueron reasignados en distintas tareas.. El Comité de Ética en Investigación del Hospital General de Niños Pedro de Elizalde presenta los distintos procedimientos implementados en esta emergencia, para sostener diferentes investigaciones, y que les permitió una rápida respuesta a esta situación.

Status of Institutional Review Board Meetings Conducted Through Web Conference Systems in Japanese National University Hospitals During the COVID-19 Pandemic: Questionnaire Study.

BACKGROUND: With the global proliferation of the novel COVID-19 disease, conventionally conducting institutional review board (IRB) meetings has become a difficult task. Amid concerns about the suspension of drug development due to delays within IRBs, it has been suggested that IRB meetings should be temporarily conducted via the internet. OBJECTIVE: This study aimed to elucidate the current status of IRB meetings conducted through web conference systems. METHODS: A survey on conducting IRB meetings through web conference systems was administered to Japanese national university hospitals. Respondents were in charge of operating IRB offices at different universities. This study was not a randomized controlled trial. RESULTS: The survey was performed at 42 facilities between the end of May and early June, 2020, immediately after the state of emergency was lifted in Japan. The survey yielded a response rate of 74% (31/42). Additionally, while 68% (21/31) of facilities introduced web conference systems for IRB meetings, 13% (4/31) of the surveyed facilities postponed IRB meetings. Therefore, we conducted a further survey of 21 facilities that implemented web conference systems for IRB meetings. According to 71% (15/21) of the respondents, there was no financial burden for implementing these systems, as they were free of charge. In 90% (19/21) of the facilities, IRB meetings through web conference systems were already being conducted with personal electronic devices. Furthermore, in 48% (10/21) of facilities, a web conference system was used in conjunction with face-to-face meetings. CONCLUSIONS: Due to the COVID-19 pandemic, the number of reviews in clinical trial core hospitals has decreased. This suggests that the development of pharmaceuticals has stagnated because of COVID-19. According to 71% (15/21) of the respondents who conducted IRB meetings through web conference systems, the cost of introducing such meetings was US $0, showing a negligible financial burden. Moreover, it was shown that online deliberations could be carried out in the same manner as face-to-face meetings, as 86% (18/21) of facilities stated that the number of comments made by board members did not change. To improve the quality of IRB meetings conducted through web conference systems, it is necessary to further examine camera use and the content displayed on members' screens during meetings. Further examination of all members who use web conference systems is required. Our measures for addressing the requests and problems identified in our study could potentially be considered protocols for future IRB meetings, when the COVID-19 pandemic has passed and face-to-face meetings are possible again. This study also highlights the importance of developing web conference systems for IRB meetings to respond to future unforeseen pandemics.

Ethical and research governance approval across Europe: Experiences from three European palliative care studies.

BACKGROUND: Research requires high-quality ethical and governance scrutiny and approval. However, when research is conducted across different countries, this can cause challenges due to the differing ethico-legal framework requirements of ethical boards. There is no specific guidance for research which does not involve non-medicinal products. AIM: To describe and address differences in ethical and research governance procedures applied by research ethics committees for non-pharmaceutical palliative care studies including adult participants in collaborative European studies. DESIGN: An online survey analysed using descriptive statistics. SETTING/PARTICIPANTS: Eighteen principal investigators in 11 countries conducting one of three European-funded studies. RESULTS: There was variation in practice including whether ethical approval was required. The time to gain full approvals differed with the United Kingdom having governance procedures that took the longest time. Written consent was not required in all countries nor were data safety monitoring committees for trials. There were additional differences in relation to other data management issues. CONCLUSION: Researchers need to take the differences in research approval procedures into account when planning studies. Future research is needed to establish European-wide recommendations for policy and practice that dovetail ethical procedures and enhance transnational research collaborations.

Comprehensive survey among statistical members of medical ethics committees in Germany on their personal impression of completeness and correctness of biostatistical aspects of submitted study protocols.

OBJECTIVES: To assess biostatistical quality of study protocols submitted to German medical ethics committees according to personal appraisal of their statistical members. DESIGN: We conducted a web-based survey among biostatisticians who have been active as members in German medical ethics committees during the past 3 years. SETTING: The study population was identified by a comprehensive web search on websites of German medical ethics committees. PARTICIPANTS: The final list comprised 86 eligible persons. In total, 57 (66%) completed the survey. QUESTIONNAIRE: The first item checked whether the inclusion criterion was met. The last item assessed satisfaction with the survey. Four items aimed to characterise the medical ethics committee in terms of type and location, one item asked for the urgency of biostatistical training addressed to the medical investigators. The main 2×12 items reported an individual assessment of the quality of biostatistical aspects in the submitted study protocols, while distinguishing studies according to the German Medicines Act (AMG)/German Act on Medical Devices (MPG) and studies non-regulated by these laws. PRIMARY AND SECONDARY OUTCOME MEASURES: The individual assessment of the quality of biostatistical aspects corresponds to the primary objective. Thus, participants were asked to complete the sentence 'In x% of the submitted study protocols, the following problem occurs', where 12 different statistical problems were formulated. All other items assess secondary endpoints. RESULTS: For all biostatistical aspects, 45 of 49 (91.8%) participants judged the quality of AMG/MPG study protocols much better than that of 'non-regulated' studies. The latter are in median affected 20%-60% more often by statistical problems. The highest need for training was reported for sample size calculation, missing values and multiple comparison procedures. CONCLUSIONS: Biostatisticians being active in German medical ethics committees classify the biostatistical quality of study protocols as low for 'non-regulated' studies, whereas quality is much better for AMG/MPG studies.

An overview of ethical review committees in Japan: examining the certification applications of ethical review committees.

The survey involves examining the applications from 142 institutions that have consented to make available all certification applications from 2015 and 2016 to a research project for building a certification system for an ethics committee run by the Agency for Medical Research and Development. The number of certified institutions is 20 (14.1%). In the applications from uncertified institutions, there are cases in which requirements of ethics guidelines are unmet, and there is insufficient information provided on regulation and procedure. An analysis of the committee members who can contribute as members of the general public (general public committee members) has indicated that the number of committee members who do not belong to an institution in which an ethics committee is instituted (external committee members) is 41 (95.7%) among the certified institutions and 224 (84.5%) among the uncertified institutions. The proportion of general public committee members drawn internally from institutions tends to be higher among uncertified institutions. While a separate committee examined conflicts of interest in research in 19 certified institutions (95.0%), such conflicts were found in 41 uncertified institutions (33.9%) by the ethics committee. The survey confirms that the challenge lies in increasing the number of external committee members and in further improving the system to manage conflicts of interest, and the education and training regime.

Huge variation in obtaining ethical permission for a non-interventional observational study in Europe.

BACKGROUND: Ethical approval (EA) must be obtained before medical research can start. We describe the differences in EA for an pseudonymous, non-interventional, observational European study. METHODS: Sixteen European national coordinators (NCs) of the international study on very old intensive care patients answered an online questionnaire concerning their experience getting EA. RESULTS: N = 8/16 of the NCs could apply at one single national ethical committee (EC), while the others had to apply to various regional ECs and/or individual hospital institutional research boards (IRBs). The time between applying for EA and the first decision varied between 7 days and 300 days. In 9/16 informed consent from the patient was not deemed necessary; in 7/16 informed consent was required from the patient or relatives. The upload of coded data to a central database required additional information in 14/16. In 4/16 the NCs had to ask separate approval to keep a subject identification code list to de-pseudonymize the patients if questions would occur. Only 2/16 of the NCs agreed that informed consent was necessary for this observational study. Overall, 6/16 of the NCs were satisfied with the entire process and 8/16 were (very) unsatisfied. 11/16 would welcome a European central EC that would judge observational studies for all European countries. DISCUSSION: Variations in the process and prolonged time needed to get EA for observational studies hampers inclusion of patients in some European countries. This might have a negative influence on the external validity. Further harmonization of ethical approval process across Europe is welcomed for low-risk observational studies. CONCLUSION: Getting ethical approval for low-risk, non-interventional, observational studies varies enormously across European countries.

A Rare Opportunity: Examining the Experience of a New Institutional Review Board.

The process of creating a new Institutional Review Board (IRB) or Research Ethics Committee (REC) presents many challenges; however, little has been published to describe this experience. Thus, many questions about creating a new IRB/REC and the challenges they face remain. The establishment of a new federal-wide single IRB provided a rare opportunity to describe these experience and outcomes. A census of the activity and outcomes of this new board is reported for its first 3 years of operation: The convened board approved 50 protocols, required an average of 93.24 days and 2.76 reviews for protocol approval, and issued an average of 31.82 stipulations per protocol. The census data helped to identify several issues that impacted the board's outcomes and it serves as a baseline for future comparisons. The overall dynamics, challenges, and outcomes of this new single IRB are discussed.

Resource use, costs, and approval times for planning and preparing a randomized clinical trial before and after the implementation of the new Swiss human research legislation.

BACKGROUND: The preparation of a randomized controlled trial (RCT) requires substantial resources and the administrative processes can be burdensome. To facilitate the conduct of RCTs it is important to better understand cost drivers. In January 2014 the enactment of the new Swiss Legislation on Human Research (LHR) considerably changed the regulatory framework in Switzerland. We assess if the new LHR was associated with change in (i) resource use and costs to prepare an RCT, and (ii) approval times with research ethics committees (RECs) and the regulatory authority Swissmedic. METHODS: We surveyed investigators of RCTs which were approved by RECs in 2012 or in 2016 and asked for RCT preparation costs using a pre-specified item list. Additionally, we collected approval times from RECs and Swissmedic. RESULTS: The response rates of the investigator survey were 8.3% (19/228) for 2012 and 16.5% (47/285) in 2016. The median preparation cost of an RCT was USD 72,400 (interquartile range [IQR]: USD 59,500-87,700; n = 18) in 2012 and USD 72,600 (IQR: USD 42,800-169,600; n = 35) in 2016. For single centre RCTs a median REC approval time of 82 (IQR: 49-107; n = 38) days in 2012 and 92 (IQR: 65-131; n = 63) days in 2016 was observed. The median Swissmedic approval time for any clinical trial was 27 (IQR: 19-51; n = 213) days in 2012 and 49 (IQR: 36-67; n = 179) days in 2016. The total duration for achieving RCT approval from both authorities (REC and Swissmedic) in the parallel submission procedure applied in 2016 could not be assessed. CONCLUSION: Based on limited data the costs to plan and prepare RCTs in Switzerland were approximately USD 72,000 in 2012 and 2016. For effective and valid research on costs and approval times of RCTs a greater willingness to share cost information among investigators and more collaboration between stakeholders with data linkage is necessary.

Saúde e pesquisa científica com seres humanos: a conformação dos danos decorrentes e o modelo brasileiro de fiscalização / Health and scientific research with human beings: the conformation of the resulting damages and the brazilian method of inspection / Salud e investigación científica con seres humanos: la conformación de los daños resultantes y el modelo brasileño de fiscalización

Objetivo: Este artigo objetiva analisar o ordenamento jurídico brasileiro às pesquisas envolvendo seres humanos no tocante aos danos à saúde decorrentes dos experimentos, com fundamento na Resolução nº 466/2012 do Conselho Nacional de Saúde. Metodologia: Realizou-se pesquisa de natureza bibliográfica, em livros e artigos da área jurídica, em legislações ordinárias e resoluções relacionadas, bem como em artigos publicados em periódicos da área de Saúde. Resultados: Os danos decorrentes dos experimentos devem ser cuidadosamente evitados e, se ocorrerem, deve o participante da pesquisa ser indenizado. Conclusão: Eventuais danos decorrentes dos experimentos devem ser evitados e observados durante todo o curso da pesquisa, iniciando-se com a assinatura do Termo de Consentimento Livre e Esclarecido pelo participante e perpassando pela fiscalização pelo Comitê Nacional de Ética e Pesquisa e pelas Comissões de Ética em Pesquisa. É essencial que o acompanhamento e a fiscalização sejam feito de forma mais próxima, obstando e ressarcindo a ocorrência de eventuais danos, além de garantir a regularidade do processo de consentimento realizado no projeto

Objective: This article objectives to analyze the legal treatment and the procedure adopted by Brazil on clinical research with basis on the Resolution nº 466/2012 from National Health Council towards the occurrence of damages due to the project. Methodology: The research was carried out in nature bibliographical references, in books and articles of the legal area, in ordinary legislations and related resolutions, as well as in articles published in periodicals of the Health area. Results: Damages must be avoided and, when occurring, must provide also an compensation to those who were harmed. Conclusion: Any damages resulting from the experiments should be avoid and noted during the curse of the project, since the moment of the informed consent's signature to the stage of inspection from the National Ethics and Research Committee and Research Ethics Committees. The completion of a closest monitoring is essential to prevent this damages and to indemnify the participant. Furthermore, it guarantees that the process of consent is being held on a satisfactory form

. Objetivos: Trabajo destinado al análisis jurídico de la protección conferida por el ordenamiento brasileño a las investigaciones involucrando a seres humanos en lo que se refiere a los daños a la salud derivados de los experimentos, con base en la Resolución 466/2012 del Consejo Nacional de Salud. Metodología: Se realizó investigación de naturaleza bibliográfica, en libros y artículos del área jurídica, en legislaciones ordinarias y resoluciones relacionadas, así como en artículos publicados en periódicos del área de Salud. Resultados: Los daños resultantes de los experimentos deben ser cuidadosamente evitados y, si ocurren, el participante de la investigación debe ser indemnizado. Conclusión: Eventuales daños resultantes de los experimentos deben ser evitados y observados durante todo el curso de la investigación, iniciándose con la firma del Término de Consentimiento Libre y Esclarecido por el participante y pasando por la fiscalización por el Comité Nacional de Ética e Investigación y por las Comisiones de Ética en Investigación. Es esencial que el seguimiento y la fiscalización se haga de forma más cercana, obstaculizando y resarciendo la ocurrencia de eventuales daños, además de garantizar la regularidad del proceso de consentimiento realizado en el proyecto

Site Variability in Regulatory Oversight for an International Study of Pediatric Sepsis.

OBJECTIVES: Duplicative institutional review board/research ethics committee review for multicenter studies may impose administrative burdens and inefficiencies affecting study implementation and quality. Understanding variability in site-specific institutional review board/research ethics committee assessment and barriers to using a single review committee (an increasingly proposed solution) can inform a more efficient process. We provide needed data about the regulatory oversight process for the Sepsis PRevalence, OUtcomes, and Therapies multicenter point prevalence study. DESIGN: Survey. SETTING: Sites invited to participate in Sepsis PRevalence, OUtcomes, and Therapies. SUBJECTS: Investigators at sites that expressed interest and/or participated in Sepsis PRevalence, OUtcomes, and Therapies. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Using an electronic survey, we collected data about 1) logistics of protocol submission, 2) institutional review board/research ethics committee requested modifications, and 3) use of a single institutional review board (for U.S. sites). We collected surveys from 104 of 167 sites (62%). Of the 97 sites that submitted the protocol for institutional review board/research ethics committee review, 34% conducted full board review, 54% expedited review, and 4% considered the study exempt. Time to institutional review board/research ethics committee approval required a median of 34 (range 3-186) days, which took longer at sites that required protocol modifications (median [interquartile range] 50 d [35-131 d] vs 32 d [14-54 d)]; p = 0.02). Enrollment was delayed at eight sites due to prolonged (> 50 d) time to approval. Of 49 U.S. sites, 43% considered using a single institutional review board, but only 18% utilized this option. Time to final approval for U.S. sites using the single institutional review board was 62 days (interquartile range, 34-70 d) compared with 34 days (interquartile range, 15-54 d) for nonsingle institutional review board sites (p = 0.16). CONCLUSIONS: Variability in regulatory oversight was evident for this minimal-risk observational research study, most notably in the category of type of review conducted. Duplicative review prolonged time to protocol approval at some sites. Use of a single institutional review board for U.S. sites was rare and did not improve efficiency of protocol approval. Suggestions for minimizing these challenges are provided.

Independent Review Of Research Proposals From Ethical Point Of View In Pakistan.

BACKGROUND: Ethics is a part of subject philosophy and gained importance in research after the Nuremberg Code that led to Helsinki's Declaration on research ethics. In most developed countries stringent measures are taken to implement ethics in research. Awareness is on the rise in developing countries too. METHODS: This cross-sectional part of mixed methods design of study is part of a PhD thesis. Data was collected from medical institutions including medical colleges, medical universities, dental colleges, and teaching hospitals of Pakistan. Questionnaires were developed, and final version was adopted after pretesting. Questionnaires were sent via registered post. RESULTS: A total of 78 institutions responded. Out of 78, 48 (61.5%) were in public sector and 30(38.5%) in private sector. Seventy-four (94%) had institutional review boards. The numbers of members ranged from 1 to 15 with 40(54%) having number of members from 3 to 7. Out of 74 with IRBs, 17(23%) had members from community, 11(15%) had religious scholars and 8(11%) had members from legal background. Sixty-four (86.5%) responded that they had time frames for research proposal processing that ranged from one to 26 weeks (6.2±5.6). CONCLUSIONS: It is concluded that most of the medical institutions where research is conducted and approved through deficient research ethical boards in terms of their constitution. Research ethics is not a priority area for most of the institutions. Representation of society at large is missing. National action is required at government level.

Time to institutional review board approval with local versus central review in a multicenter pragmatic trial.

BACKGROUND/AIMS: Central institutional review board (IRB) review will be required for National Institutes of Health-funded multisite human subjects research as of January 2018, with similar requirements extending to most US multisite human research in 2020. Nonetheless, little is known regarding the relative efficiency of central versus local IRB review for multicenter studies. We compared the amount of time required for central versus local IRB review and approval for sites in one ongoing multicenter randomized trial. METHODS: The REGAIN Trial (Regional versus General Anesthesia for Promoting Independence after Hip Fracture; clinicaltrials.gov number: NCT02507505) is an ongoing randomized trial comparing standard-care spinal anesthesia to standard-care general anesthesia for patients undergoing hip fracture surgery. After approval of the protocol by the sponsor IRB, each participating US site opted either to submit the protocol for local IRB review or to designate the sponsor IRB as the IRB of record (i.e. central IRB) via an authorization agreement after a limited local review. For each US REGAIN site approved through 18 April 2017, we assessed (1) the time in calendar days from protocol receipt to IRB submission, (2) the time in calendar days from IRB submission to IRB approval, and (3) the total time in calendar days from protocol receipt to IRB approval (i.e. time from protocol receipt to IRB submission plus time from IRB submission to IRB approval). RESULTS: The main study protocol was submitted to the sponsor IRB on 25 May 2015 and approved on 8 July 2015 (44 days). Out of 34 sites, 9 received initial approval from the central (sponsor) IRB; 25 sought initial approval via local review. The median time from protocol receipt to IRB submission was 39 days for sites approved by the central IRB (interquartile range: 35-134) versus 58 days for sites approved via local review (interquartile range: 41-105; p = 0.711). The median time from IRB submission to IRB approval for sites approved by the central IRB was 27 days (interquartile range: 14-32) versus 66 days (interquartile range: 29-138) for sites approved via local review (p = 0.026). The median total time from protocol receipt to IRB approval was 100 days (interquartile range: 71-148) for centrally approved sites versus 132 days (interquartile range: 87-209) for locally approved sites (p = 0.191). CONCLUSION: While central IRB review was associated with a shorter time from IRB submission to IRB approval compared to local IRB review, the total time from protocol receipt to IRB approval varied markedly across sites.

Institutional Scientific Review of Cancer Clinical Research Protocols: A Unique Requirement That Affects Activation Timelines.

PURPOSE: The National Cancer Institute (NCI) requirement that clinical trials at NCI-designated cancer centers undergo institutional scientific review in addition to institutional review board evaluation is unique among medical specialties. We sought to evaluate the effect of this process on protocol activation timelines. METHODS: We analyzed oncology clinical trials that underwent full board review by the Harold C. Simmons Comprehensive Cancer Center Protocol Review and Monitoring Committee (PRMC) from January 1, 2009, through June 30, 2013. We analyzed associations between trial characteristics, PRMC decisions, protocol modifications, and process timelines using the χ2 test, Fisher's exact test, Wilcoxon rank sum test, Kruskal-Wallis test, and logistic regression. RESULTS: A total of 226 trials were analyzed. Of these, 77% were industry sponsored and 23% were investigator initiated. The median time from submission to PRMC approval was 55 days. The length of review was associated with trial phase, timing of approval, and number of committee changes/clarifications requested. The median process time was 35 days for those approved at first decision, 68 days for second decision, and 116 days for third decision ( P < .001). The median process time was 39 days if no changes/clarifications were requested, 64 days for one to three changes/clarifications, and 73 days for four or more changes/clarifications ( P < .001). Requested changes/clarifications had a greater effect on industry-sponsored trials than on investigator-initiated trials. CONCLUSION: NCI-mandated institutional scientific review of oncology clinical trials contributes substantially to protocol activation timelines. Further evaluation of this process and the value added to research quality is warranted.

Inadequacy of ethical conduct and reporting of stepped wedge cluster randomized trials: Results from a systematic review.

Background/aims The use of the stepped wedge cluster randomized design is rapidly increasing. This design is commonly used to evaluate health policy and service delivery interventions. Stepped wedge cluster randomized trials have unique characteristics that complicate their ethical interpretation. The 2012 Ottawa Statement provides comprehensive guidance on the ethical design and conduct of cluster randomized trials, and the 2010 CONSORT extension for cluster randomized trials provides guidelines for reporting. Our aims were to assess the adequacy of the ethical conduct and reporting of stepped wedge trials to date, focusing on research ethics review and informed consent. Methods We conducted a systematic review of stepped wedge cluster randomized trials in health research published up to 2014 in English language journals. We extracted details of study intervention and data collection procedures, as well as reporting of research ethics review and informed consent. Two reviewers independently extracted data from each trial; discrepancies were resolved through discussion. We identified the presence of any research participants at the cluster level and the individual level. We assessed ethical conduct by tabulating reporting of research ethics review and informed consent against the presence of research participants. Results Of 32 identified stepped wedge trials, only 24 (75%) reported review by a research ethics committee, and only 16 (50%) reported informed consent from any research participants-yet, all trials included research participants at some level. In the subgroup of 20 trials with research participants at cluster level, only 4 (20%) reported informed consent from such participants; in 26 trials with individual-level research participants, only 15 (58%) reported their informed consent. Interventions (regardless of whether targeting cluster- or individual-level participants) were delivered at the group level in more than two-thirds of trials; nine trials (28%) had no identifiable data collected from any research participants. Overall, only three trials (9%) indicated that a waiver of consent had been granted by a research ethics committee. When considering the combined requirement of research ethics review and informed consent (or a waiver), only one in three studies were compliant. Conclusion The ethical conduct and reporting of key ethical protections in stepped wedge trials, namely, research ethics review and informed consent, are inadequate. We recommend that stepped wedge trials be classified as research and reviewed and approved by a research ethics committee. We also recommend that researchers appropriately identify research participants (which may include health professionals), seek informed consent or appeal to an ethics committee for a waiver of consent, and include explicit details of research ethics approval and informed consent in the trial report.

Time required to review research protocols at 10 Veterans Affairs Institutional Review Boards.

BACKGROUND: Despite perceptions that institutional review boards (IRBs) delay research, little is known about how long it takes to secure IRB approval. We retrospectively quantified IRB review times at 10 large Veterans Affairs (VA) IRBs. METHODS: We collected IRB records pertaining to a stratified random sample of research protocols drawn from 10 of the 26 largest VA IRBs. Two independent analysts abstracted dates from the IRB records, from which we calculated overall and incremental review times. We used multivariable linear regression to assess variation in total and incremental review times by IRB and review level (i.e., exempt, expedited, or full board) and to identify potential targets for efforts to improve the efficiency and uniformity of the IRB review process. RESULTS: In a sample of 277 protocols, the mean review time was 112 d (95% confidence interval [CI]: 105-120). Compared with full-board reviews at IRB 1, average review times at IRBs 3, 8, 9, and 10 were 27 (95% CI: 6-48), 37 (95% CI: 11-63), 45 (95% CI: 20-69), and 24 (95% CI: 2-45) d shorter, and at IRB 6, times were 56 (95% CI: 28-84) d longer. Across all IRBs, expedited reviews were 44 (95% CI: 30-58) d shorter on average than were full-board reviews, with no significant difference between exempt and full-board reviews. However, after subtracting the time required for Research and Development Committee review, exempt reviews were 21 (95% CI: 1-41) d shorter on average than were full-board reviews. CONCLUSIONS: IRB review times differ significantly by IRB and review level. Few VA IRBs approach a consensus panel goal of 60 d for IRB review. The unexpectedly longer review times for exempt protocols in the VA can be attributed to time required for Research and Development Committee review. Prospective, routine collection of key time points in the IRB review process could inform IRB-specific initiatives for reducing VA IRB review times.

How Much Participant Outcome Data Is Missing from Sight: Findings from a Cohort of Trials Submitted to a German Research Ethics Committee.

BACKGROUND: Study publication bias and outcome reporting bias have been recognised as two threats to the validity of systematic reviews. The purpose of this research was to estimate the proportion of missing participant outcome data from randomised controlled trials (RCTs) due to lack of publication of whole studies and due to outcome data missing within study publications. METHODS AND FINDINGS: Data were extracted from protocols of clinical research projects submitted to the research ethics committee of the University of Freiburg (Germany) between 2000 and 2002 and associated fully published articles. The total amount of published and unpublished outcome data from all trial participants was calculated for each trial and the overall proportion of missing data from both unpublished and published trials computed. Full and partially reported outcome data was also taken into consideration. The impact of funding source on missingness was also considered at the trial level. From 308 parallel group trials in the study cohort, 167 were published and 141 were unpublished. Overall, 260,563 participants contributed to a total of 2,618,116 participant outcome data across all trials. About half (47%) of the participant outcome data from the 308 trials was reported in full but at least 81% were partially reported. Of the 19% of participant data that were missing, 4% was attributable to missing data from published trials and 15% from unpublished trials. Commercially funded trials had a higher probability of publication (relative risk 1.20, 95% confidence interval 0.86, 1.67; p = 0.27) but were less likely to fully report all outcomes than non-commercially funded trials (relative risk 0.64, 95% confidence interval 0.30, 1.38; p = 0.26). CONCLUSIONS: Missing participant outcome data from both published and unpublished trials is frequent. Clinical trial registration including outcome information not only identifies that clinical trials exist but the systematic examination and monitoring of trial information within a registry can help detect selective reporting of entire studies and of outcome data within studies and possibly prevent it.

Do Chinese Researchers Conduct Ethical Research and Use Ethics Committee Review in Clinical Trials of Anti-Dementia Drugs? An Analysis of Biomedical Publications Originating from China.

BACKGROUND: Medical research using human participants must conform to the basic ethical principles found in the Declaration of Helsinki (DoH) of the World Medical Association. OBJECTIVE: The purpose of this review was to assess whether journals in China have improved in regard to the fulfillment of ethical disclosure procedures for clinical trials of anti-dementia drugs. METHODS: Four medical databases were searched for articles reporting clinical trials of oral anti-dementia drugs published in China in 2003, 2009, and 2014. The frequencies of reporting of informed consent from participants (ICP), approval of a regional ethical committee (REC), reference to DoH, and study registration were estimated respectively. Statistical analyses were conducted with SPSS v21 software. RESULTS: Among those randomized controlled trials published in 2003, 2009, and 2014, disclosure of REC approval was present for 2.67%, 1.15%, and 6.84%; statements of ICP were included in 9.33%, 7.76%, and 17.34%; reference to DoH was found for 4.00%, 1.44%, and 7.45%; and study registration reporting was included in 2.67%, 2.59%, and 9.28%, respectively. Improvements to reporting rates between 2009 and 2014 were seen, with more than twice as many trials reporting REC approval, ICP, reference to DoH, and study registration compared with 2009. CONCLUSION: Compared with 2003 and 2009, reporting rates for REC approval, ICP, reference to DoH, and study registration for clinical trials of anti-dementia drugs were enhanced in 2014 in the major medical journals of China. However, biomedical publications without definite statements of ethical considerations remain common, and this continues to be seen in Chinese journals. It is imperative that measures are taken to reinforce the ethical protection in clinical trials in China.

Identifying Repetitive Institutional Review Board Stipulations by Natural Language Processing and Network Analysis.

The corrections ("stipulations") to a proposed research study protocol produced by an institutional review board (IRB) can often be repetitive across many studies; however, there is no standard set of stipulations that could be used, for example, by researchers wishing to anticipate and correct problems in their research proposals prior to submitting to an IRB. The objective of the research was to computationally identify the most repetitive types of stipulations generated in the course of IRB deliberations. The text of each stipulation was normalized using the natural language processing techniques. An undirected weighted network was constructed in which each stipulation was represented by a node, and each link, if present, had weight corresponding to the TF-IDF Cosine Similarity of the stipulations. Network analysis software was then used to identify clusters in the network representing similar stipulations. The final results were correlated with additional data to produce further insights about the IRB workflow. From a corpus of 18,582 stipulations we identified 31 types of repetitive stipulations. Those types accounted for 3,870 stipulations (20.8% of the corpus) produced for 697 (88.7%) of all protocols in 392 (also 88.7%) of all the CNS IRB meetings with stipulations entered in our data source. A notable peroportion of the corrections produced by the IRB can be considered highly repetitive. Our shareable method relied on a minimal manual analysis and provides an intuitive exploration with theoretically unbounded granularity. Finer granularity allowed for the insight that is anticipated to prevent the need for identifying the IRB panel expertise or any human supervision.