Reporting and design of randomized controlled trials for COVID-19: A systematic review

Alison Dillman, Jay J H Park, Michael J Zoratti, Noor-E Zannat, Zelyn Lee, Louis Dron, Grace Hsu, Gerald Smith, Sahand Khakabimamaghani, Ofir Harari, Kristian Thorlund, Edward J Mills, Alison Dillman, Jay J H Park, Michael J Zoratti, Noor-E Zannat, Zelyn Lee, Louis Dron, Grace Hsu, Gerald Smith, Sahand Khakabimamaghani, Ofir Harari, Kristian Thorlund, Edward J Mills

Abstract

Background: The novel coronavirus 2019 (COVID-19) pandemic has mobilized global research at an unprecedented scale. While challenges associated with the COVID-19 trial landscape have been discussed previously, no comprehensive reviews have been conducted to assess the reporting, design, and data sharing practices of randomized controlled trials (RCTs).

Purpose: The purpose of this review was to gain insight into the current landscape of reporting, methodological design, and data sharing practices for COVID-19 RCTs.

Data sources: We conducted three searches to identify registered clinical trials, peer-reviewed publications, and pre-print publications.

Study selection: After screening eight major trial registries and 7844 records, we identified 178 registered trials and 38 publications describing 35 trials, including 25 peer-reviewed publications and 13 pre-prints.

Data extraction: Trial ID, registry, location, population, intervention, control, study design, recruitment target, actual recruitment, outcomes, data sharing statement, and time of data sharing were extracted.

Data synthesis: Of 178 registered trials, 112 (62.92%) were in hospital settings, median planned recruitment was 100 participants (IQR: 60, 168), and the majority (n = 166, 93.26%) did not report results in their respective registries. Of 35 published trials, 31 (88.57%) were in hospital settings, median actual recruitment was 86 participants (IQR: 55.5, 218), 10 (28.57%) did not reach recruitment targets, and 27 trials (77.14%) reported plans to share data.

Conclusions: The findings of our study highlight limitations in the design and reporting practices of COVID-19 RCTs and provide guidance towards more efficient reporting of trial results, greater diversity in patient settings, and more robust data sharing.

Keywords: Coronavirus; Novel coronavirus 2019; Randomized controlled trials; Systematic literature review.

Conflict of interest statement

The authors do not have any competing interests.

Copyright © 2020 Elsevier Inc. All rights reserved.

Figures

Fig. 1
Fig. 1
Study flow diagram.

References

    1. Sohrabi C., Alsafi Z., O’Neill N., et al. World Health Organization declares global emergency: a review of the 2019 novel coronavirus (COVID-19) Int. J. Surg. 2020;76:71–76.
    1. McCoy D., Chand S., Sridhar D. Global health funding: how much, where it comes from and where it goes. Health Policy Plan. 2009;24(6):407–417.
    1. Thorlund K., Dron L., Park J., Hsu G., Forrest J.I., Mills E.J. A real-time dashboard of clinical trials for COVID-19. Lancet Digit Health. 2020;2(6):e286–e287.
    1. Bauchner H., Golub R.M., Zylke J. Editorial concern—possible reporting of the same patients with COVID-19 in different reports. JAMA. 2020;323(13):1256.
    1. Glasziou P.P., Sanders S., Hoffmann T. Waste in covid-19 research. BMJ. 2020;369:m1847.
    1. Bauchner H., Fontanarosa P.B., Golub R.M. Editorial evaluation and peer review during a pandemic: how journals maintain standards. JAMA. 2020;324(5):453–454.
    1. Kwon D. How swamped preprint servers are blocking bad coronavirus research. Nature. 2020;581(7807):130–131.
    1. Dexamethasone in hospitalized patients with Covid-19 — Preliminary reportN. Engl. J. Med. 2020:1–11. Epub ahead of print. NEJMoa2021436.
    1. Majumder M.S., Mandl K.D. Early in the epidemic: impact of preprints on global discourse about COVID-19 transmissibility. Lancet Glob. Health. 2020;8(5):e627–e630.
    1. Arabi Y.M., Murthy S., Webb S. COVID-19: a novel coronavirus and a novel challenge for critical care. Intensive Care Med. 2020:1–4.
    1. Moher D., Liberati A., Tetzlaff J., Altman D.G. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Ann. Intern. Med. 2009;151(4):264–269.
    1. COVID-19 SARS-CoV-2 preprints from medRxiv and bioRxivmedRxiv. 2020 (Accessed 8 July 2020)
    1. Palayew A., Norgaard O., Safreed-Harmon K., Andersen T.H., Rasmussen L.N., Lazarus J.V. Pandemic publishing poses a new COVID-19 challenge. Nat. Hum. Behav. 2020;4(7):666–669.
    1. Bauchner H., Fontanarosa P.B. Randomized clinical trials and COVID-19: managing expectations. JAMA. 2020;04:04.
    1. Higgins J.P., Altman D.G., Gotzsche P.C., et al. The cochrane collaboration’s tool for assessing risk of bias in randomised trials. BMJ. 2011;343:d5928.
    1. Horby P., Lim W.S., Emberson J., et al. Effect of dexamethasone in hospitalized patients with COVID-19: preliminary report. medRxiv. 2020 (2020.2006.2022.20137273)
    1. Beigel J.H., Tomashek K.M., Dodd L.E., et al. Remdesivir for the treatment of Covid-19 - preliminary report. N. Engl. J. Med. 2020;22:22.
    1. Cao B., Wang Y., Wen D., et al. A trial of Lopinavir-ritonavir in adults hospitalized with severe Covid-19. N. Engl. J. Med. 2020;382(19):1787–1799.
    1. Gharbharan A., Jordans C.C.E., GeurtsvanKessel C., et al. Convalescent Plasma for COVID-19. A randomized clinical trial. medRxiv. 2020 (2020.2007.2001.20139857)
    1. Wang Y., Zhang D., Du G., et al. Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial. Lancet. 2020;395(10236):1569–1578.
    1. Wu C.N., Xia L.Z., Li K.H., et al. High-flow nasal-oxygenation-assisted fibreoptic tracheal intubation in critically ill patients with COVID-19 pneumonia: a prospective randomised controlled trial. Br. J. Anaesth. 2020;125(1):e166–e168.
    1. Walport M., Brest P. Sharing research data to improve public health. Lancet. 2011;377(9765):537–539.
    1. Heymann D.L. Data sharing and outbreaks: best practice exemplified. Lancet. 2020;395(10223):469–470.
    1. Cao Y., Wei J., Zou L., et al. Ruxolitinib in treatment of severe coronavirus disease 2019 (COVID-19): a multicenter, single-blind, randomized controlled trial. J. Allergy Clin. Immunol. 2020;26:26.
    1. Li L., Zhang W., Hu Y., et al. Effect of convalescent plasma therapy on time to clinical improvement in patients with severe and life-threatening COVID-19: a randomized clinical trial. Jama. 2020;03:03.
    1. Tang W., Cao Z., Han M., et al. Hydroxychloroquine in patients with mainly mild to moderate coronavirus disease 2019: Open label, randomised controlled trial. BMJ. 2020;369 (no pagination)
    1. Li Y., Xie Z., Lin W., et al. Efficacy and safety of lopinavir/ritonavir or arbidol in adult patients with mild/moderate COVID-19: an exploratory randomized controlled trial. Med. 2020
    1. Hague W.E., Gebski V.J., Keech A.C. Recruitment to randomised studies. Med. J. Aust. 2003;178(11):579–581.
    1. Boulware D.R., Pullen M.F., Bangdiwala A.S., et al. A randomized trial of hydroxychloroquine as Postexposure prophylaxis for Covid-19. N. Engl. J. Med. 2020;03:03.
    1. Bierer B.E., Li R., Barnes M., Sim I. A global, neutral platform for sharing trial data. N. Engl. J. Med. 2016;374(25):2411–2413.
    1. Baker S.R., Bloom N., Davis S.J., Terry S.J. Covid-induced economic uncertainty. Nation. Bureau Econ. Res. 2020:0898–2937.
    1. Fauci A.S., Lane H.C., Redfield R.R. Covid-19—navigating the uncharted. Mass Med. Soc. 2020;382:1268–1269.
    1. Amat-Santos I.J., Santos-Martinez S., Lopez-Otero D., et al. Ramipril in high risk patients with COVID-19. J. Am. Coll. Cardiol. 2020;22:22.
    1. Borba M.G.S., Val F.F.A., Sampaio V.S., et al. Effect of high vs low doses of chloroquine diphosphate as adjunctive therapy for patients hospitalized with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection: a randomized clinical trial. JAMA Netw. Open. 2020;3(4)
    1. Chen J., Liu D., Liu L., et al. A pilot study of hydroxychloroquine in treatment of patients with moderate COVID-19. Zhejiang Da Xue Xue Bao Yi Xue Ban. 2020;49(2):215–219.
    1. Christensen L., Rasmussen C.S., Benfield T., Franc J.M. A randomized trial of instructor-led training versus video lesson in training health care providers in proper donning and doffing of personal protective equipment. Disaster Med. 2020:1–15.
    1. Goldman J.D., Lye D.C.B., Hui D.S., et al. Remdesivir for 5 or 10 days in patients with severe Covid-19. N. Engl. J. Med. 2020;27
    1. Hu K., Guan W.J., Bi Y., et al. Efficacy and safety of Lianhuaqingwen capsules, a repurposed Chinese herb, in patients with coronavirus disease 2019: a multicenter, prospective, randomized controlled trial. Phytomedicine. 2020 Article 153242.
    1. Hung I.F., Lung K.C., Tso E.Y., et al. Triple combination of interferon beta-1b, lopinavir-ritonavir, and ribavirin in the treatment of patients admitted to hospital with COVID-19: an open-label, randomised, phase 2 trial. Lancet. 2020;395(10238):1695–1704.
    1. Li J., Wang X., Huang X., et al. Application of CareDose 4D combined with Karl 3D technology in the low dose computed tomography for the follow-up of COVID-19. BMC Med. Imaging. 2020;20(1):56.
    1. Liu K., Chen Y., Wu D., Lin R., Wang Z., Pan L. Effects of progressive muscle relaxation on anxiety and sleep quality in patients with COVID-19. Complement. Ther. Clin. Pract. 2020;39:101132.
    1. Liu K., Zhang W., Yang Y., Zhang J., Li Y., Chen Y. Respiratory rehabilitation in elderly patients with COVID-19: a randomized controlled study. Complement. Ther. Clin. Pract. 2020;39:101166.
    1. Mitjà O., Corbacho-Monné M., Ubals M., et al. Hydroxychloroquine for early treatment of adults with mild Covid-19: a randomized-controlled trial. Clin. Infect. Dis. 2020 (Article: ciaa1009)
    1. Skipper C.P., Pastick K.A., Engen N.W., et al. Hydroxychloroquine in nonhospitalized adults with early COVID-19. Ann. Intern. Med. 2020;173(8):623–631.
    1. Wei N., Huang B.C., Lu S.J., et al. Efficacy of internet-based integrated intervention on depression and anxiety symptoms in patients with COVID-19. J Zhejiang Univ Sci B. 2020;21(5):400–404.
    1. Wen L., Zhou Z., Jiang D., Huang K. Effect of Xuebijing injection on inflammatory markers and disease outcome of coronavirus disease 2019. [Chinese] Zhonghua Wei Zhong Bing Ji Jiu Yi Xue. 2020;32(4):426–429.
    1. Ye Y.A. Guideline-based Chinese herbal medicine treatment plus standard care for severe coronavirus disease 2019 (G-CHAMPS): evidence from China. Front. Med. 2020;7 (no pagination)
    1. Deftereos S.G., Giannopoulos G., Vrachatis D.A., et al. Effect of colchicine vs standard care on cardiac and inflammatory biomarkers and clinical outcomes in patients hospitalized with coronavirus disease 2019: the GRECCO-19 randomized clinical trial. JAMA Netw. Open. 2020;3(6):e2013136.
    1. Yuan X., Yi W., Liu B., et al. Pulmonary radiological change of COVID-19 patients with 99mTc-MDP treatment. medRxiv. 2020 2020.2004.2007.20054767.
    1. Chen Z., Hu J., Zhang Z., et al. Efficacy of hydroxychloroquine in patients with COVID-19: results of a randomized clinical trial. medRxiv. 2020 2020.2003.2022.20040758.
    1. Chen L., Zhang Z.-Y., Fu J.-G., et al. Efficacy and safety of chloroquine or hydroxychloroquine in moderate type of COVID-19: a prospective open-label randomized controlled study. medRxiv. 2020 2020.2006.2019.20136093.
    1. Chen C., Zhang Y., Huang J., et al. Favipiravir versus arbidol for COVID-19: a randomized clinical trial. medRxiv. 2020 2020.2003.2017.20037432.
    1. Zhong M., Sun A., Xiao T., et al. A Randomized, single-blind, group sequential, active-controlled study to evaluate the clinical efficacy and safety of α-Lipoic acid for critically ill patients with coronavirus disease 2019(COVID-19) medRxiv. 2020 2020.2004.2015.20066266.
    1. Zheng F., Zhou Y., Zhou Z., et al. A novel protein drug, novaferon, as the potential antiviral drug for COVID-19. medRxiv. 2020 2020.2004.2024.20077735.
    1. Lou Y., Liu L., Qiu Y. Clinical outcomes and plasma concentrations of baloxavir marboxil and favipiravir in COVID-19 patients: an exploratory randomized, controlled trial. medRxiv. 2020 2020.2004.2029.20085761.
    1. Davoudi-Monfared E., Rahmani H., Khalili H., et al. Efficacy and safety of interferon beta-1a in treatment of severe COVID-19: A randomized clinical trial. medRxiv. 2020 2020.2005.2028.20116467.

Source: PubMed

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