Objective: To describe the methodological characteristics and good research practices of the intervention studies for COVID-19 developed in Brazil in the first months of the pandemic. Method: A review in the CONEP-COVID bulletin (05/28/2020) and the International Clinical Trials Registry Platform, ClinicalTrials.gov, ReBEC was conducted to identify drug-type, biological therapy or vaccine intervention studies registered in Brazil. The studies were evaluated for methodological characteristics and power for different magnitudes of effect. Results: 62 studies were included, 55 identified on the CONEP website and seven on a registration database. Several interventions are being tested: chloroquine/hydroxychloroquine, azithromycin, plasma convalescent, tocilizumab, sarilumab, eculizumab, vaccine, corticoids, anticoagulants, n-acetylcysteine, nitazoxanide, ivermectin, lopinavir/ritonavir, etc. By May 2020, 22 research protocols were published in a protocol registry database, 82% were randomized clinical trials and 59% had adequate control group. However, 59% were not masked and only 24% included patients with positive test with diagnostic accuracy. Most of the studies would have power >80% just to identify large effect sizes. In a prospective follow-up, until July 21st/2020, 60% of the studies available at CONEP were not registered in the ICTRP/ReBEC/ClinicalTrials platforms. Conclusion: The interventions evaluated during the Brazilian research response reflect international initiatives, but with a different distribution, a larger proportion of studies asseessed hydroxychloroquine/chloroquine. Limitations in methodological design and sample planning represent challenges that could affect the research outreach.

Objetivo: Descrever as características metodológicas e de boas práticas em pesquisa dos estudos de intervenção para COVID-19 desenvolvidos no Brasil nos primeiros meses da pandemia. Método: Revisamos o boletim da CONEP-COVID (28/05/2020) e as bases International Clinical Trials Registry Platform, ClinicalTrials.gov e ReBEC para identificar estudos registrados no Brasil, avaliando intervenções de tipo medicamento, terapia biológica ou vacinas. Descrevemos as características metodológicas e calculamos o poder para diferentes magnitudes de efeito. Resultados: Foram incluídos 62 estudos, 55 identificados no site da CONEP e mais sete nas bases de registro. As intervenções medicamentosas mais frequentemente testadas nesses estudos foram: cloroquina/hidroxicloroquina, azitromicina, plasma convalescente, tocilizumabe, sarilumabe, eculizumabe, vacina, corticoides, anticoagulantes, n-acetilcisteína, nitazoxanida, ivermectina e lopinavir/ritonavir. De 22 protocolos, publicados até maio de 2020 nas bases de registro, 18 (82%) eram ensaios clínicos randomizados e 13 (59%) tinham grupo controle adequado. Entretanto, nove (41%) eram mascarados e somente cinco (24%) incluía pacientes diagnosticados com teste de laboratório específico (e.g. RT-PCR). A maioria desses trabalhos teria poder >80% apenas para identificar grandes tamanhos de efeito. Em seguimento prospectivo, observamos que 60% dos estudos, disponíveis na CONEP até maio de 2020, não estava em nenhuma das plataformas de registro (ICTRP/ReBEC/ClinicalTrials) até o dia 21/07/2020.Conclusão: As intervenções avaliadas durante a resposta brasileira em pesquisa refletem iniciativas internacionais, porém com uma distribuição diferente, tendo um número elevado de estudos avaliando hidroxicloroquina/ cloroquina. Limitações no delineamento metodológico e planejamento amostral representam desafios que poderiam afetar o alcance dos trabalhos.

Clinical trials investigating COVID-19 treatments have been carried out worldwide, and also in Brazil. Public registration of research protocols promotes transparency and follows the legislation. Objective: To describe the research protocols under development in Brazil for COVID-19 treatment, and to evaluate the publication after registration in Plataforma Brasil/CONEP. Method: A comprehensive search on the databases ClinicalTrials.gov, ReBEC (Brazilian database) and the International Clinical Trials Registry Platform, was performed on April 11, 2020. The CONEP Bulletin was consulted on April 7, 2020 to assess intervention studies elected for public registration. Results: Our study shows that there are sixteen intervention studies in progress about COVID-19 in Brazil (CONEP registry), however, only six are available in the protocol registry databases. Brazilian open access research protocols investigated interventions with: hydroxychloroquine associated with azithromycin or monotherapy; chloroquine; dexamethasone; mesenchymal stem cells. Five studies (83%) are open and include patients with suspected or confirmed COVID-19 diagnosis. Three studies are multicenter and all include clinically relevant outcomes. Conclusion: Brazil has research protocols in progress for COVID-19 treatment, however only 1/3 of these studies has public protocols available.

As pesquisas clínicas relacionadas a COVID-19 estão acontecendo em todo o mundo, inclusive no Brasil. Os registros públicos de protocolos de pesquisa promovem transparência e atendem às regulamentações. Objetivo: Descrever os protocolos de pesquisa em desenvolvimento no Brasil para investigações de alternativas terapêuticas para a COVID-19, e avaliar o cumprimento da publicação após registro na Plataforma Brasil/CONEP. Método: Uma revisão foi realizada nas bases de registro de protocolos de pesquisa: ClinicalTrials.gov,  ReBEC (base brasileira) e International Clinical Trials Registry Platform, no dia 11 de abril de 2020. O boletim da CONEP do dia 07 de abril de 2020 foi consultado para avaliar estudos de intervenção passíveis de registro. Resultados: Nosso estudo mostrou que há dezesseis estudos de intervenção sobre a COVID-19 em andamento no Brasil e registrados na CONEP, porém somente seis estão disponíveis nas bases de registro de protocolos. Os protocolos brasileiros de acesso aberto incluíram a investigação de intervenções com: hidroxicloroquina associada a azitromicina ou em monoterapia; cloroquina; dexametasona; células tronco mesenquimais. Cinco estudos (83%) são abertos e incluíram pacientes com suspeita ou diagnóstico confirmado da COVID-19. Três estudos são multicêntricos e todos propõe a avaliação de desfechos clinicamente relevantes. Conclusão: O Brasil tem protocolos de pesquisa em andamento de intervenções terapêuticas na COVID-19, porém apenas 1/3 destes estudos têm protocolos públicos.

RESUMO: Objetivo: Descrever as características metodológicas e de boas práticas em pesquisa dos estudos de intervenção para COVID-19 desenvolvidos no Brasil nos primeiros meses da pandemia. Métodos: Revisamos o boletim da Comissão Nacional de Ética em Pesquisa - edição especial Coronavírus (CONEP-COVID) (28 de maio de 2020) e as bases International Clinical Trials Registry Platform (ICTRP), ClinicalTrials.gov e Registro Brasileiro de Ensaios Clínicos (ReBEC) para identificar estudos registrados no Brasil que avaliassem intervenções de tipo de medicamento, terapia biológica ou vacinas. Descrevemos as características metodológicas e calculamos o poder para diferentes magnitudes de efeito. Resultados: Foram incluídos 62 estudos, 55 identificados no site da CONEP e mais sete nas bases de registro. As intervenções medicamentosas mais frequentemente testadas nesses estudos foram: cloroquina/hidroxicloroquina, azitromicina, plasma convalescente, tocilizumabe, sarilumabe, eculizumabe, vacina, corticoides, anticoagulantes, n-acetilcisteína, nitazoxanida, ivermectina e lopinavir/ritonavir. De 22 protocolos publicados até maio de 2020 nas bases de registro, 18 (82%) eram ensaios clínicos randomizados e 13 (59%) tinham grupo controle adequado. Entretanto, nove (41%) eram mascarados e somente cinco (24%) incluíam pacientes diagnosticados com teste de laboratório específico (por exemplo, transcrição reversa seguida de reação em cadeia da polimerase - RT-PCR). A maioria desses trabalhos teria poder > 80% apenas para identificar grandes tamanhos de efeito. Em seguimento prospectivo, observamos que 60% dos estudos disponíveis na CONEP até maio de 2020 não estavam em nenhuma das plataformas de registro (ICTRP/ReBEC/ClinicalTrials) até o dia 21 de julho de 2020. Conclusão: As intervenções avaliadas durante a resposta brasileira em pesquisa refletem iniciativas internacionais, porém com distribuição diferente, tendo número elevado de estudos que avaliam hidroxicloroquina/cloroquina. Limitações no delineamento metodológico e planejamento amostral representam desafios que podem afetar o alcance dos trabalhos.

ABSTRACT: Objective: To describe the methodological characteristics and good research practices of COVID-19 interventional studies developed in Brazil in the first months of the pandemic. Methods: We reviewed the bulletin of the National Research Ethics Committee - Coronavirus Special Edition (Comissão Nacional de Ética em Pesquisa - CONEP-COVID) (May 28, 2020) and the databases of the International Clinical Trials Registry Platform (ICTRP), ClinicalTrials.gov, and Brazilian Clinical Trials Registry (Registro Brasileiro de Ensaios Clínicos - ReBEC) to identify interventional studies registered in Brazil that assessed drug type, biological therapy, or vaccines. We described their methodological characteristics and calculated their power for different effect magnitudes. Results: A total of 62 studies were included, 55 retrieved from the CONEP website, and 7 from registry databases. The most tested pharmacological interventions in these studies were: chloroquine/hydroxychloroquine, azithromycin, convalescent plasma, tocilizumab, sarilumab, eculizumab, vaccine, corticosteroids, anticoagulants, n-acetylcysteine, nitazoxanide, ivermectin, and lopinavir/ritonavir. Out of 22 protocols published on registry databases until May 2020, 18 (82%) were randomized clinical trials, and 13 (59%) had an appropriate control group. However, 9 (41%) of them were masked, and only 5 (24%) included patients diagnosed with a specific laboratory test (for example, reverse transcription polymerase chain reaction - RT-PCR). Most of these studies had power > 80% only to identify large effect sizes. In the prospective follow-up, 60% of the studies available at CONEP until May 2020 had not been published on any registry platform (ICTRP/ReBEC/ClinicalTrials) by July 21, 2020. Conclusion: The interventions evaluated during the Brazilian research response reflect those of international initiatives, but with a different distribution and a large number of studies assessing hydroxychloroquine/chloroquine. Limitations in methodological design and sample planning represent challenges that could affect the research outreach.

RESUMO: Objetivo: Descrever as características metodológicas e de boas práticas em pesquisa dos estudos de intervenção para COVID-19 desenvolvidos no Brasil nos primeiros meses da pandemia. Métodos: Revisamos o boletim da Comissão Nacional de Ética em Pesquisa - edição especial Coronavírus (CONEP-COVID) (28 de maio de 2020) e as bases International Clinical Trials Registry Platform (ICTRP), ClinicalTrials.gov e Registro Brasileiro de Ensaios Clínicos (ReBEC) para identificar estudos registrados no Brasil que avaliassem intervenções de tipo de medicamento, terapia biológica ou vacinas. Descrevemos as características metodológicas e calculamos o poder para diferentes magnitudes de efeito. Resultados: Foram incluídos 62 estudos, 55 identificados no site da CONEP e mais sete nas bases de registro. As intervenções medicamentosas mais frequentemente testadas nesses estudos foram: cloroquina/hidroxicloroquina, azitromicina, plasma convalescente, tocilizumabe, sarilumabe, eculizumabe, vacina, corticoides, anticoagulantes, n-acetilcisteína, nitazoxanida, ivermectina e lopinavir/ritonavir. De 22 protocolos publicados até maio de 2020 nas bases de registro, 18 (82%) eram ensaios clínicos randomizados e 13 (59%) tinham grupo controle adequado. Entretanto, nove (41%) eram mascarados e somente cinco (24%) incluíam pacientes diagnosticados com teste de laboratório específico (por exemplo, transcrição reversa seguida de reação em cadeia da polimerase - RT-PCR). A maioria desses trabalhos teria poder > 80% apenas para identificar grandes tamanhos de efeito. Em seguimento prospectivo, observamos que 60% dos estudos disponíveis na CONEP até maio de 2020 não estavam em nenhuma das plataformas de registro (ICTRP/ReBEC/ClinicalTrials) até o dia 21 de julho de 2020. Conclusão: As intervenções avaliadas durante a resposta brasileira em pesquisa refletem iniciativas internacionais, porém com distribuição diferente, tendo número elevado de estudos que avaliam hidroxicloroquina/cloroquina. Limitações no delineamento metodológico e planejamento amostral representam desafios que podem afetar o alcance dos trabalhos.

ABSTRACT: Objective: To describe the methodological characteristics and good research practices of COVID-19 interventional studies developed in Brazil in the first months of the pandemic. Methods: We reviewed the bulletin of the National Research Ethics Committee - Coronavirus Special Edition (Comissão Nacional de Ética em Pesquisa - CONEP-COVID) (May 28, 2020) and the databases of the International Clinical Trials Registry Platform (ICTRP), ClinicalTrials.gov, and Brazilian Clinical Trials Registry (Registro Brasileiro de Ensaios Clínicos - ReBEC) to identify interventional studies registered in Brazil that assessed drug type, biological therapy, or vaccines. We described their methodological characteristics and calculated their power for different effect magnitudes. Results: A total of 62 studies were included, 55 retrieved from the CONEP website, and 7 from registry databases. The most tested pharmacological interventions in these studies were: chloroquine/hydroxychloroquine, azithromycin, convalescent plasma, tocilizumab, sarilumab, eculizumab, vaccine, corticosteroids, anticoagulants, n-acetylcysteine, nitazoxanide, ivermectin, and lopinavir/ritonavir. Out of 22 protocols published on registry databases until May 2020, 18 (82%) were randomized clinical trials, and 13 (59%) had an appropriate control group. However, 9 (41%) of them were masked, and only 5 (24%) included patients diagnosed with a specific laboratory test (for example, reverse transcription polymerase chain reaction - RT-PCR). Most of these studies had power > 80% only to identify large effect sizes. In the prospective follow-up, 60% of the studies available at CONEP until May 2020 had not been published on any registry platform (ICTRP/ReBEC/ClinicalTrials) by July 21, 2020. Conclusion: The interventions evaluated during the Brazilian research response reflect those of international initiatives, but with a different distribution and a large number of studies assessing hydroxychloroquine/chloroquine. Limitations in methodological design and sample planning represent challenges that could affect the research outreach.

Abstract Falls are the second leading cause of accidental and unintentional injury deaths worldwide. Inpatient falls in hospital settings are likely to prolong the length of stay of patients in nearly 6.3 days, leading to increased hospitalization costs. The causes of fall incidents in healthcare facilities are multifactorial in nature and certain medications use could be associated with these incidents. This review seeks to critically evaluate the available literature regarding the relationship between inpatient falls and medication use. A comprehensive search was performed on MEDLINE, EMBASE and Lilacs with no time restriction. The search was filtered using English, Spanish or Portuguese languages. Our study evaluated medication use and inpatients falls that effectively happen, considering all ages and populations. An assessment of bias and quality of the studies was carried out using an adapted tool from the literature. The drugs were classified according to the Anatomic Therapeutics Chemical Code. The search strategy retrieved 563 records, among which 23 met the eligibility criteria; ninety three different pharmacological subgroups were associated with fall incidents. Our critical review suggests that the use of central nervous system drugs (including anxiolytics; hypnotics and sedatives; antipsychotics; opioids; antiepileptics and antidepressants) has a greater likelihood of causing inpatient falls. A weak relationship was found between other pharmacological subgroups, such as diuretics, cardiovascular system-related medications, and inpatient fall. Remarkably, several problems of quality were encountered with regard to the eligible studies. Among such quality problems included retrospective design, the grouping of more than one medication in the same statistical analysis, limited external validity, problems related to medication classifications and description of potential confounders.