Open access Original research Ethical frameworks in clinical research processes during COVID-19: a scoping review Lawrence Kasherman ‍ ‍,1,2,3 Ainhoa Madariaga,1,4 Qin Liu,1,5 Luisa Bonilla,1 Michelle McMullen,1,6 Shiru (Lucy) Liu,1,7 Lisa Wang,8 Rouhi Fazelzad,1 Katherine Karakasis,1 Ann M Heesters,8,9 Amit M Oza1 To cite: Kasherman L, ABSTRACT Madariaga A, Liu Q, et al. Strengths and limitations of this study Objectives In response to the COVID-19 pandemic Ethical frameworks in there have been significant developments in research, clinical research processes ►► Systematic review of existing literature for referenc- its conduct and the supporting ethical framework. While during COVID-19: a es to ethical frameworks and consent processes in many protocols have been delayed, halted or modified, scoping review. BMJ Open the context of COVID-19 pandemic. 2021;11:e047076. doi:10.1136/ other research efforts have been accelerated, generating ►► Statistical analyses of variables relevant to ethical bmjopen-2020-047076 controversy. The goal of this paper is to determine the frameworks can potentially account for variations rates of references surrounding the ethical oversight of ►► Prepublication history and including region and study type. research as reported in current COVID-19-­related research additional supplemental material ►► Documentation processes related to research eth- publications. for this paper are available ical oversight vary between countries, health sys- Design Scoping review. online. To view these files, tems and institutions. please visit the journal online Setting Population-­based observational or interventional (http://​dx.​doi.​org/​10.​1136/​ studies from December 2019 to May 2020 with sample bmjopen-​2020-​047076). size of two or more. Studies were searched through electronic databases including Medline, EMBASE, and crises. The rapid rise in worldwide incidence LK and AM contributed equally. Cochrane CENTRAL Register of Controlled Trials. of COVID-19 has created an unprecedented, Participants Eligibility criteria included participants within urgent need to learn, understand and bridge Received 18 November 2020 Accepted 14 June 2021 published studies who tested positive for COVID-19. the therapeutic gap.1 2 The international Main outcomes and measures Data were extracted scientific community has responded swiftly and charting methods included taking note of references by initiating hundreds of clinical trials, to ethical frameworks, institutional review board (IRB), evidenced on ​clinicaltrials.​gov and the WHO ethics committee (EC) or research ethics board (REB) COVID-19 databases.3 4 However, balancing involvement, consent processes, and other variables. research quality, integrity and protection of Results 11 556 articles were screened, with 656 included in the final analysis. References to ethics were present in vulnerable subjects with the apparent need 530 (80.8%) studies, with 491 (74.8%) involving IRB/ECs/ for speed on research processes are important REBs and 126 (19.2%) not referencing ethics. Consent facets which deserve attention. It is essential processes were outlined in 201 (30.6%) studies, with 198 to maintain acceptable ethical standards and (30.2%) reporting that they obtained consent waivers, scientific rigour at all times, including during however, 257 (39.2%) did not mention consent at all. global pandemics, where various aspects of Differences (p<0.001) in ethics-­related references were trial design and conduct may be modified apparent when analysed by continent, publication type, to meet shortened development timelines. sample size and IF. Vigorous debate continues with respect to the Conclusions The majority of published articles ethical standards appropriate to the protec- pertaining to COVID-19 research made mention of ethical tion of participants in times of global crisis.5 considerations, however, national and regional variations in research ethics review requirements introduce Despite well-­established existing norma- © Author(s) (or their tive guidance from national and interna- heterogeneity between studies and raise important employer(s)) 2021. Re-­use questions about the conduct of scientific research during tional bodies which set out general principles permitted under CC BY-­NC. No commercial re-­use. See rights global public emergencies. pertaining to the ethical conduct of human and permissions. Published by Trial registration number Open Science Framework: subjects research during emergency circum- BMJ. https://osfio/z67wb. stances, ultimately, the decision to approve For numbered affiliations see clinical research remains the responsibility end of article. of local or regional research review bodies.6 Correspondence to INTRODUCTION In Canada, these are known as research Dr Amit M Oza; The pandemic of COVID-19 has created ethics boards (REB). The USA has simi- ​amit.​oza@​uhn.​ca evolving healthcare, economic and social larly constituted review processes provided Kasherman L, et al. BMJ Open 2021;11:e047076. doi:10.1136/bmjopen-2020-047076 1 Open access by committees called institutional review boards (IRB). procedures and requirements of published sources Other countries may rely on ethics committees (EC).7 outside of non-­indexed journal databases. The search was Recognising the high stakes associated with ongoing restricted to original research involving human partici- exceptional circumstances affecting the global commu- pant. The search strategy for MEDLINE is presented in nity, we performed a scoping review of current literature the supplementary appendix (online supplemental file related to COVID-19 in order to identify references to 2). Additional search strategies are available from the ethical frameworks and consent processes, and correlated corresponding author on request. these with various study and publication characteristics. Study selection Search results were imported into EndNote V.X9 citation software, following which results were uploaded onto METHODS Covidence for duplicate removal, two-­ tiered screening We developed a protocol using the scoping review and data extraction. Reviewers were familiarised with the methods proposed by Arksey and O’Malley,8 and refined review protocol and eligibility criteria prior to abstract by the Joanna Briggs Institute.9 This review was registered screening and full-­text review. through the Open Science Framework (https://​osf.​io/​ A series of calibration exercises prior to each stage z67wb/). The Preferred Reporting Items for Systematic of screening to ensure reliability across reviewers was Reviews and Meta-­Analyses extension for scoping reviews10 completed. Inter-­rater agreement for study inclusion was was used to guide reporting (online supplemental file 1). calculated using per cent agreement and when it reached >75% across the research team, we proceeded to the next Eligibility criteria stage. If the per cent agreement was <75%, the inclusion Our eligibility criteria were defined using ‘Population, criteria were clarified, and another pilot test occurred. Intervention, Comparison, Outcomes, Study designs, For abstract screening, one pilot test of 50 citations was Timeframe’ components. The population of interest was conducted with all team members and we achieved 90% patients with history of active or past COVID-19 infection. agreement. Subsequently, two reviewers (LK and AM) Studies with a mixed population of COVID-19 infected independently reviewed all titles and abstracts for inclu- and non-­ infected patients were also included. Inter- sion. For full-­text screening, one pilot test of 10 full-­text ventions of interest included were studies referencing articles was conducted, and we achieved 80% agreement. drugs, devices or other interventions. Studies including Following this calibration exercise, two reviewers (LK and diagnostic laboratory or radiological procedures were AM) screened full-­text articles for inclusion. All discrep- also eligible. Outcomes of any measure were eligible for ancies between reviewers were resolved by a third reviewer inclusion. Studies included were clinical trials, observa- consistently (QL). tional studies and case series. We excluded case reports describing a single patient; trials still in progress; studies Data collection analysing population-­ based database-­ driven, aggregate For each study, data were abstracted on ethical frame- or pooled data; non-­COVID-19 infected subjects; studies works referenced (defined as any reference to any ethics, described only in social media; and surveys surrounding participant consent or institutional or ethics committee medical workforce, health services or staff attitudes. We review), including whether an IRB, REB or EC was involved restricted the timeframe from 1 December 2019 to 8 May in approving the study, as well as description of consent 2020, at which time the literature search was performed. processes (including alterations of consent processes such We excluded studies without full-­text available, and due as waivers of the requirement to obtain consent). Other to the rapid nature of the review those not available in the variables extracted included type of publication (brief English language were excluded. communication vs letter vs original research vs case report); month of first availability online; countries involved; single Information sources and search strategy site versus multicentre study; sample size; study population The protocol for the comprehensive literature search was (COVID-19 positive or both positive and negative); and developed by an experienced information specialist (RF) longitudinal nature (prospective vs retrospective vs cross-­ in consultation with the research team and was completed sectional). A pilot test of 12 articles was conducted with by the information specialist. Due to the rapid nature of inter-­rater agreement of 82%. The data abstraction form the review, the search was limited to publications in the was developed and modified as required based on feed- English language from December 2019 to May 2020. A back from the team. Studies were distributed among six comprehensive search was conducted in Medline ALL reviewers (LK, AM, QL, MM, LB and SLL), and data were (Medline and Epub Print Ahead of Print and In-­ Pro- cross-­checked by two reviewers (LK and AM). Any discrep- cess and Other Non-­Indexed Citations), EMBASE and ancies were resolved through consensus. The information Cochrane CENTRAL Register of Controlled Trials all specialist (RF) extracted impact factor (IF) for each journal. from the OvidSP platform. Where provided, controlled vocabulary terms and text words were compromised. Methodological quality appraisal Grey literature was not searched as the reviewers felt it Quality appraisal and risk of bias of studies were not was beyond the scope of this review to analyse the ethical assessed as this was a scoping review. 2 Kasherman L, et al. BMJ Open 2021;11:e047076. doi:10.1136/bmjopen-2020-047076 Open access studies were eligible for full-­text review, following which 656 were included in the qualitative synthesis. The full reference list is included in online supplemental file 4. Ethical frameworks referenced A reference to ethics or consent was made in 530 (80.8%) studies, with 491 (74.8%) involving IRB/EC/REB. One hundred and twenty-­six (19.2%) records did not refer- ence ethics in any way. Consent processes were referenced in 201 (30.6%) studies, 198 (30.2%) described a consent waiver and 257 (39.2%) made no mention of consent. Correlation with other variables There were no interactions between rates of reference to ethics, REB/IRB/EC or consent processes when comparing study populations or centres (figure 2, addi- tional data in online supplemental file 5). Most (n=595, 91%) were first available or published from March to May 2020, however further analyses were not performed. Continent In terms of where studies were done, the majority were from Asia (n=488, 74.4%), Europe (n=92, 14%) and North America (n=62, 9.5%), with largest contribu- tions from China (n=438, 66.8%), USA (62, 9.5%) and Italy (n=51, 7.8%) and studies with largest sample sizes coming from the former two regions (see figure 3). Figure 1 Preferred Reporting Items for Systematic Reviews and Meta-­Analyses (2009) diagram of literature search. Studies from Asia were more likely to reference ethical frameworks (86.3%, p<0.001) and REB/IRB/EC (81.6%, p<0.001) compared with Europe (64.1%, 53.3%) and Data synthesis and charting North America (64.5%, 56.5%). The mention of consent Extracted data points were compiled into an Excel spread- processes was also more common among studies from sheet, from which descriptive statistical analyses were Asia, with 33.2% (p<0.001) obtaining consent and 33.6% generated. Due to heterogeneity, types of publication were (p<0.001) obtaining a waiver of consent, compared with condensed into four categories (online supplemental file Europe (30.4%, 11.96% waiver) and North America 3). Study countries were condensed into continents for (8.1%, 32.3% waiver). Subgroup analyses by continent analysis, with subgroup analyses of countries with high are presented in the supplementary appendix (online frequencies. For those without ethics referenced within supplemental figures 1 and 2). each continent, analyses were performed broken down by sample size and type of publication. The association Publication type between a continuous variable and a categorical vari- With respect to type of publication (figure 2A–C), the able was determined by using Wilcoxon and Kruskal-­ majority were original research pieces (n=485, 73.9%), Willis tests, respectively, to compare continuous variables followed by brief communications (n=91, 13.9%), letters between two and more than three groups, whereas the χ2 (n=54, 8.2%) and case reports (n=26, 4%). Studies test was used to compare categorical variables, unless the described as case reports had a sample size of at least two underlying assumptions were not satisfied. In that case, (range: 2– 191, median 3). Original research was more we used a Fisher’s exact test. Sample size was analysed as likely (p<0.001) to reference ethics (87%) compared with a continuous variable, as well as dichotomous variables brief communications (62.6%), case reports (53.9%) or with cut-­offs of 3 and 10 participants. Analyses on IF were letters (68.5%). REB/IRB/EC approval/waiver was performed as continuous and dichotomous variables, also mentioned more frequently (p<0.001) in orig- focusing on those within Scientific Journal Ranking Quar- inal research (83.1%), and likewise in terms of consent tile 1 (lower cut-­off 2.32) in ‘Medicine (miscellaneous)’ processes (32%) or waivers (33.4%, p<0.001). compared with the remainder.11 Study type In terms of study design (figure 2G–I), most studies were RESULTS observational (n=545, 83.1%). Only 13 (2%) were inter- The electronic database search obtained 11 556 results ventional drug studies and 14 (2%) were described as (figure 1). A total of 3527 duplicates were removed and interventional ‘other’ studies. Reference to ethics was 8029 records underwent abstract screening. A total of 836 not significantly different (p=0.16) between study types Kasherman L, et al. BMJ Open 2021;11:e047076. doi:10.1136/bmjopen-2020-047076 3 Open access Figure 2 Ethics referenced, researchethics board/institutionalreview board/ethicscommittee involved and consent process described by publication type (A–B), centre (D–F), type of study (G–I), longitudinal nature (J–L), proportion of sample size greater than three, or three or less (M–O), proportion of sample size greater than 10, or 10 or less (P–R), study population (S–U) and impact factor (V–X). P values provided reflect statistical significance of interaction using Fisher’s exact test. 4 Kasherman L, et al. BMJ Open 2021;11:e047076. doi:10.1136/bmjopen-2020-047076 Open access Figure 3 Graphical distribution by country of (A) sample size of included studies and (B) study density. and REB/IRB/EC reference was borderline significant Sample size (p=0.04). Consent processes were statistically significantly The median study sample size was 59 (range: 2–257 353). different (p<0.001), with 3 (23.1%) out of 13 interven- Of the 530 studies referencing ethics, the median sample tional drug studies and 5 (35.7%) out of 14 interventional size was 72 (range: 2–257 353) compared with 126 in those ‘other’ studies not referencing consent. No consent that did not reference ethics (range: 2–7425, p<0.001). processes were described in 37 (44.1%) diagnostic and The differences in median sample size were also signifi- 212 (38.9%) observational studies. cantly different when comparing rates of REB/IRB/EC (p<0.001) and consent process (p<0.001) references. Longitudinal nature When dichotomising sample size comparisons using In terms of longitudinal nature (figure 2J–L), the majority a cut-­off of 3 (figure 2M–O) or 10 (figure 2P–R), all of studies were retrospective (n=520, 79.3%), followed by interactions were significantly different (p<0.001) across prospective (n=102, 15.5%), cross-­sectional (n=25, 3.8%) ethics, REB/IRB/EC references and consent processes. and not reported (n=9, 1.4%). There were no differ- Of the 599 studies with sample size greater than 3, 84.1% ences in rates of references to ethics (p=0.28) or refer- (n=504) referenced ethics compared with 45.6% (n=26) ences to REB/IRB/EC (p=0.27). Consent was more often of 57 articles with sample size of 3 or less. When the cut-­ described in non-­ retrospective studies (p<0.001), with off was increased to 10, 61.2% (n=93) of 152 studies with nearly twice the rates of waivers (n=174, 33.46%) being sample size of 10 or less referenced ethics as compared granted in retrospective studies compared with the rest. with 86.7% (n=437) of 504 studies with more than Consent processes were not described in 33 (32.35%) 10 patients. Similar trends were observed with lower rates prospective studies. of studies that did not mention REB/IRB/EC references Kasherman L, et al. BMJ Open 2021;11:e047076. doi:10.1136/bmjopen-2020-047076 5 Open access or consent processes when analysis cut-­off was increased International ethical guidelines for health-­related research involving humans https://cioms.ch/publications/product/international- National ethical guidelines for biomedical and health research involving humans https://ethics.ncdirindia.org//asset/pdf/ICMR_ from sample size of 3 to 10. CFR, Code of Federal Regulations; CIOMS, Council for International Organizations of Medical Sciences; GCP, Good Clinical Practice; ICH, International Conference Harmonization; ICMR, Impact factor IF was available for 631 (96.2%) studies, with a median retrieveECFR?gp=&SID=83cd09e1c0f5c6937cd9d7513160fc3f&pitd=20180719&n=pt45.1.46&r=PART&ty=HTML of 4.62 (range: 0.86–74.7). The median IF of articles with ethics referenced (n=530) was 4.83 (range: 0.86–74.7) 50: Protection of Human Subjects https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm compared with a median of 4.16 (range: 1.11–74.7, 56: Institutional Review Boards https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm Ethical conduct for research involving humans http://publications.gc.ca/site/eng/381622/publication.html p=0.06) in those with no ethics referenced (n=126). For Quartile 1 (median: 5.6, range: 2.327–74.699), 428 (82.6%) of 518 articles referenced ethics compared International ethical and scientific quality standard https://www.fda.gov/media/93884/download with 102 (73.9%) of 138 articles within non-­Quartile 1 journals (median: 1.911, range: 0.86–2.286, p=0.03; see figure 2V–X). The interactions were not statistically signif- icant when analysed by REB/IRB/EC reference (p=0.27) or consent process (p=0.19). DISCUSSION The main objective of this scoping review was to assess the prevalence of references to ethical concerns in original ethical-guidelines-for-health-related-research-involving-humans/ research involving patients with COVID-19 . We detected that 19.2% of published studies reported no mention of ethical framework or oversight process, with an additional 6% of studies not referring to review board approval or waiver. The obligation of researchers to attend to the welfare, rights and interests of human participants is not dimin- ished in Public Health Emergencies such as the COVID-19 pandemic. During times when public goals may be in tension with the interests of individual research partici- 46: Protection of human subjects. pants, there is heightened need for attention to ethical National_Ethical_Guidelines.pdf https://www.ecfr.gov/cgi-bin/ principles and for oversight bodies and review mecha- nisms attuned to specific vulnerabilities of those who may Research standard examples for human research protection be subject to the attention of researchers. Indian Council of Medical Research; TCPS, Tri-­Council Policy Statement. Historically, three main ethical codes have shaped contemporary research principles. The first well-­ recognised ethical code that established international research standards was the Nuremberg Code,12 which was Summary created in response to the Nuremberg trials at the end of the Second World War. In 1964, the Declaration of Helsinki (now in its seventh iteration) established ethical prin- ciples for medical research involving human subjects.13 Lastly, the Belmont Report, written in 1978, articulated three main ethical principles applicable to the conduct International International of human subject’s research: respect for persons, benef- Country Canada icence and justice.14 Current normative standards and India USA USA research regulations show variation across different coun- tries, but most express respect for these fundamental principles (table 1). Research standards At the institutional level, research review commit- CIOMS and WHO tees (REB/IRB/EC) assess the ethical acceptability of human research conducted within their jurisdictions. ICH GCP E6 CFR Title 21 CFR Title 45 The committee model is designed to protect participants TCPS 2 Table 1 from harm by ensuring that physical and non-­physical ICMR risks of study participation are not overlooked in the rush to achieve scientific breakthroughs. 6 Kasherman L, et al. BMJ Open 2021;11:e047076. doi:10.1136/bmjopen-2020-047076 Open access The gold standard for ethical research is the voluntary explained by variable journal requirements with respect and ongoing informed consent from legally competent to statements on ethics in studies involving human partic- individuals or authorised third parties prior to the initia- ipation. Differing publication types may also explain this tion of research-­related procedures. Even access to iden- variation; our analysis supports the interpretation that tifiable patient data generally requires consent; although original research articles are more likely to reference departures from usual consent processes may be justified ethical approval and consent processes as compared if requisite institutional or other approvals are secured.15 with other types of publications. Increased emphasis and Under exceptional circumstances, permission to deviate transparency is needed about how research participants from usual processes may be granted provided partici- and their rights were protected and this should be rein- pants’ rights are protected and appropriate institutional forced in published scientific research. Organisations authorisations are obtained.15 In this review, we detected such as the Committee on Publication Ethics (COPE),18 a large proportion of studies without consent processes which aims to promote integrity in scholarly research mentioned (39.2%), while 30.2% described a consent and publication, may view our findings with concern. waiver and 30.6% obtained informed consent. The COPE Core Practices suggest that all journals should Although informed consent to research ordinarily is have robust, well-­described and documented procedures, obtained in the form of signed documents, other means, including policies pertaining to consent, vulnerably situ- including verbal and electronic,16 may be appropriate ated populations, research conducted on human subjects when paper records may be vectors for disease transmis- and confidential handling of data.18 Following this guid- sion. In order to maintain the research quality standards ance, reviewers might, for example request copies of study and to ensure protection of vulnerable research partici- protocols or evidence of ethics review board approvals, pants, journals should request information about consent which could assist in inhibiting the publication of ethi- processes at the time of article submission and ensure cally problematic research. appropriate declarations within submitted manuscripts. This study has several limitations. The majority of Additionally, where applicable, the scientific commu- included studies were observational, contributing to nity should consider incorporating written or electronic lower rates of references to ethics. This was likely due consent process documentation as supplementary mate- to the timing of study conceptualisation and database rial related to all original research involving interventions, searching, which preceded the publication of many inter- participant data or biological samples. Ethical principles ventional studies. While the authors attempted to iden- and requirements should not be compromised during a tify subcategories of types of publication included for pandemic, and any changes in processes must ensure the analysis, there is heterogeneity with respect to journal rights and safety of subjects are not emasculated. requirement. Furthermore, study assessment for prospec- Our review excluded single case reports. Arguably, they tive or retrospective nature was unclear for a number of do not meet the definition of research as they do not consti- records, which may reflect on publication clarity. Finally, tute systematic investigations and are not undertaken the authors acknowledge that results generated from this with prior research intent.17 Approaches to the review review rely on studies across the globe, and documenta- and reporting of case reports vary between institutions tion processes related to research ethical oversight vary and jurisdictions, but frequently medical record reviews between countries, health systems and institutions. of three or fewer individuals do not require oversight by institutional review committees. However, ethical consid- erations should be mentioned in all studies regardless of CONCLUSION the sample size. We detected that the median sample size The ethical conduct of scientific research requires atten- in studies with ethics referenced was lower than in those tion to timeliness, innovation, feasibility and quality, without ethics referenced (72 vs 126, p<0.001). while preserving the safety, well-­being and rights of partic- Journal IF can sometimes positively correlate with ipants. Flexibility may be required during extenuating number of citations; interestingly we detected that the circumstances, however, processes must retain respect for manuscripts published in Quartile 1 journals were more the principles of ethical research. Trying times present likely to include references to ethics compared with important opportunities to ensure oversight and processes others (82.6% vs 73.9%, p=0.03). It is worth noting that are in place to maintain research and ethical rigour, and there were no significant differences in REB/IRB/EC identify permissible variations in practice. Priority should review or consent processes between these two groups. be given to developing novel strategies which accelerate We also demonstrate that while the rates of REB/IRB/ research in a safe, meaningful manner in concert with EC approval or waiver mentioned are similar to rates of relevant ethical, regulatory and funding bodies. Adap- whether ethics was referenced at all, a small proportion of tive trial designs represent larger-­scale studies which can studies with ethics referenced did not mention whether adhere to regulatory requirements while also permitting REBs/IRBs/ECs were involved (table 1 and figure 2). shorter development timelines. The current pandemic Instead, a clause on consent only, or a general statement has created opportunities to rethink efficiency in clinical not specifying what approval was sought was included. research conduct, but also highlights the importance of The disparity between these two proportions could be defining and maintaining ethical oversight. Kasherman L, et al. BMJ Open 2021;11:e047076. doi:10.1136/bmjopen-2020-047076 7 Open access This scoping review found that although the majority includes any translated material, BMJ does not warrant the accuracy and reliability of research published during this time of global stress of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error was conducted in the context of some form of ethical and/or omissions arising from translation and adaptation or otherwise. review, there is considerable variability and may reflect Open access This is an open access article distributed in accordance with the important gaps in process or reporting. An important Creative Commons Attribution Non Commercial (CC BY-­NC 4.0) license, which lesson from the current outbreak is that existing ethical permits others to distribute, remix, adapt, build upon this work non-­commercially, norms cannot be overlooked and should continuously be and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use revisited. While it is a truism that poor science can never is non-­commercial. See: http://​creativecommons.​org/​licenses/​by-​nc/​4.​0/. be ethical, poor ethics cannot be redeemed or justified by valid science or good intentions. Research participants ORCID iD have a right to expect their sacrifices will be honoured Lawrence Kasherman http://​orcid.​org/​0000-​0001-​7576-​8565 by devoting appropriate attention to both aspects of the scientific enterprise. REFERENCES Author affiliations 1 Bindra RS, Gibson SL, Meng A, et al. Hypoxia-­Induced 1 down-­regulation of BRCA1 expression by E2Fs. Cancer Res Division of Medical Oncology and Hematology, Princess Margaret Hospital Cancer Centre, Toronto, Ontario, Canada 2005;65:11597–604. 2 2 Remuzzi A, Remuzzi G. COVID-19 and Italy: what next? The Lancet Department of Medical Oncology, St George Hospital, Kogarah, New South Wales, 2020;395:1225–8. Australia 3 Tentori L, Lacal PM, Muzi A, et al. Poly(ADP-­ribose) polymerase 3 St George and Sutherland Clinical Schools, University of New South Wales, (PARP) inhibition or PARP-1 gene deletion reduces angiogenesis. Eur Kogarah, New South Wales, Australia J Cancer 2007;43:2124–33. 4 Autonomous University of Barcelona, Barcelona, Spain 4 Madariaga A, Kasherman L, Karakasis K, et al. Optimizing clinical 5 Department of Haematology, St George Hospital, Kogarah, New South Wales, research procedures in public health emergencies. Med Res Rev 2021;41:725–38. Australia 5 Blumenthal-­Barby J. COVID-19 current controversies. J Med Ethics 6 Department of Medical Oncology, Sir Charles Gairdner Hospital, Nedlands, Western 2020;46:419–20. Australia, Australia 6 World Health Organization. Guidance for managing ethical issues in 7 British Columbia Cancer Agency, Surrey, British Columbia, Canada infectious disease outbreaks. Geneva: World Health Organization, 8 University of Toronto, Toronto, Ontario, Canada 2016. https://​apps.​who.​int/​iris/​handle/​10665/​250580 9 University Health Network, Toronto, Ontario, Canada 7 Emanuel EJG, Crouch Robert A, Reidar K, et al, eds. The Oxford textbook of clinical research ethic. Oxford; New York: Oxford University Press, 2008. Twitter Lawrence Kasherman @LKasherman and Ainhoa Madariaga @ainhoamada 8 Arksey H, O'Malley L. Scoping studies: towards a methodological framework. Int J Soc Res Methodol 2005;8:19–32. Contributors LK and AM were involved in study conceptualisation, methodology, 9 Peters MDJ, Godfrey C, McInerney P. Chapter 11: scoping abstract and full-­text screening, data extraction and crosschecking, draft writing, reviews (2020 version). In: Aromataris E, Munn Z, eds. JBI manual review and final editing, creation of figures and tables. QL, LB, MM and SLL helped for evidence synthesis. Adelaide, Australia: JBI, 2020. https://​ in data extraction, writing review and final editing. LW was responsible for data synthesismanual.​jbi.​global analysis, creation of figures, writing review and final editing. RF was involved in 10 Tricco AC, Lillie E, Zarin W, et al. PRISMA extension for scoping methodology, writing review and final editing. KK helped in study conceptualisation, reviews (PRISMA-­ScR): checklist and explanation. Ann Intern Med methodology, writing review and final editing. AMH and AMO were involved in study 2018;169:467–73. 11 SJR. Scimago Journal & Country Rank, 2020. Available: https://www.​ conceptualisation, supervision, methodology, writing review and final editing. scimagojr.​com/​journalrank.​php?​area=​2700&​category=​2701 Funding The authors have not declared a specific grant for this research from any 12 The Nuremberg Code (1947). BMJ 1996;313:1448. funding agency in the public, commercial or not-­for-­profit sectors. 13 World Medical Association. World Medical association Declaration of Helsinki: ethical principles for medical research involving human Map disclaimer The depiction of boundaries on the map(s) in this article does not subjects. JAMA 2013;310:2191–4. imply the expression of any opinion whatsoever on the part of BMJ (or any member 14 United States. The Belmont report: ethical principles and guidelines of its group) concerning the legal status of any country, territory, jurisdiction or for the protection of human subjects of research. Bethesda, Md.: The area or of its authorities. The map(s) are provided without any warranty of any kind, Commission, 1978. either express or implied. 15 Canadian Institutes of Health Research. Natural sciences and engineering Research Council of Canada, and social sciences Competing interests None declared. and humanities Research Council of Canada, Tri-­Council policy statement: ethical conduct for research involving humans, December Patient consent for publication Not required. 2018, 2020. Available: https://​ethics.​gc.​ca/​eng/​documents/​tcps2-​ Provenance and peer review Not commissioned; externally peer reviewed. 2018-​en-​interactive-​final.​pdf 16 Welch BM, Marshall E, Qanungo S, et al. Teleconsent: a novel Data availability statement Data are available upon reasonable request. All data approach to obtain informed consent for research. Contemp Clin utilised for this study are available from the corresponding author upon request. Trials Commun 2016;3:74–9. 17 University Health Network Research Ethics Board. UHN REB Supplemental material This content has been supplied by the author(s). It has guidance on case reports, 2020. Available: https://www.​uhnresearch.​ not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been ca/​documents_​and_​forms/​send_​doc/​15106 peer-­reviewed. Any opinions or recommendations discussed are solely those 18 Committee on Publication Ethics. Promoting integrity in of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and scholarly research and its publication, 2020. Available: https://​ responsibility arising from any reliance placed on the content. Where the content publicationethics.​org/ 8 Kasherman L, et al. BMJ Open 2021;11:e047076. doi:10.1136/bmjopen-2020-047076