Table 1 Qualitative spectrum of challenges and potential solutions in the review of COVID-19 trial proposals by research ethics committees (RECs)
Ethical principles | Challenges (sub-categories with examples of original responses) | Potential solutions (sub-categories with examples of original responses) |
|---|---|---|
Social value | Lack of coordination/structures in study planning Frequent simultaneous planning of several COVID-19 studies within an individual hospital and uncoordinated submission of studies to the local REC Large number of small studies that partly overlap thematically and are often poorly structured Lack of concrete objectives | Coordination A multitude of studies could be coordinated at the institutional level Priority setting The urgency of studies in the current pandemic situation should be balanced. Several projects could be carried out retrospectively. More detailed assessment of the expected knowledge gains should be performed |
Scientific validity | Insufficient information for RECs Scarce or incomplete proposals or study protocols Frequent lack of biometrics Insufficient disclosure of the funding Lack of detailed description of data management or the consent process (for non-AMG/MPG* studies) Difficulty evaluating valid/relevant endpoints when the knowledge of the disease is still uncertain, leading to difficulties in calculating sample sizes Poor, provisional study planning/lack of clear objectives/insufficient statistics Study protocols with the character of a rough sketch Lack of clear rationale Lack of documentation of independent factors influencing the outcome of the study Insufficient number of planned study participants Questionable study design selected for proof of efficacy Poorly prepared and elaborated surveys/registry studies Unclear length of the study (e.g. patients should be included as long as the pandemic lasts) Frequent requirement of revisions/changes to primary and secondary endpoints Lack of clarity regarding whether the proposal reflects a clinical study or experimental treatment according to national law (“individueller Heilversuch “) Provision of statistical advice in advance rarely possible In interventional studies, frequent inadequacy of sample size calculations (e.g. initially only small sample sizes, which are then continuously increased) Lack of applicant knowledge of which guidelines they should follow | Better information Requests from experts (e.g. for suggested biometrics) and additional REC meetings to discuss proposals in detail could be adopted Studies could be subdivided into one main study with the possibility of submitting (ethically more problematic) sub-studies via amendments If the essential aspects of the trial are evident from the proposal documents and there are no fundamental concerns, a positive vote with comments is given, indicating which aspects still must be supplemented in the study protocol Pragmatic assessment of initial proposal could be tolerated if an interim evaluation were planned Improvement of study planning and advisory process Documents could be prepared with the help of institutional core facilities for clinical studies Telephone/online advice could be offered In REC counselling, a focus could be placed on scientific aspects, and (if possible) proposal formalities could be reduced A statistician could be involved; an analysis plan and clear research objectives could be required Additionally, the REC chair could contact principal investigator/sponsor for quick clarification of questions/problems COVID-19-specific assistance with the application process could be offered The REC should contact statistician before voting If there are too few COVID-19 patients locally, multicentre studies with a sufficient number of patients could be required |
Informed consent | Informed consent for patients unable to give consent For intensive care patients, a lack of an informed consent process, with the reasoning that these patients for the study are unable to give consent (according to national law: § 9 para. 2 GDPR) Lack of clarity regarding how patients can be included in clinical studies when no patient-representative is appointed or available Acceptance of verbal consent by some studies Inability to give consent, even among non-intubated patients, due to the severity of the disease Unclear whether additional, explicit consent for taking biospecimens should be required Processing of consent via telephone without a description of documentation and verifiability Problems obtaining consent from caregivers if they are not allowed to come to the hospital Restricted possibility of consulting/informing relatives due infection control measures Lack of permission for consent document to leave the patient’s room due to infection control measures Formal problems with consent Partial unavailability of patient information Lack of comprehensibility, unclear wording, Lack of information about data protection Too many AMG/MPG* amendments; difficulties ensuring that the content is checked | Alternative forms of consent Patients unable to give informed consent may be presented with the documents after they have gained the ability to give consent Consent can be given by legal representatives; additionally, subsequent signatures of the legal representatives by post or fax should be considered More detailed description in the study protocol of the process of including patients who are unable to give consent could be provided For pure data collection where only clinical routine data are to be collected for secondary use, there is no time pressure. In this case, it is possible to wait until the patient is either able to give consent again or a legal representative who can give consent has been identified. The data can then be entered retrospectively as soon as consent has been obtained. If the patient were to die in the meantime, the data could be recorded anonymously In the case of deceased persons, samples could be required to be anonymous, and no identifying research (whole or partial genome sequencing) would be carried out A photo of the signed consent form can be archived outside the patient room Formal improvement Comprehensibility could be improved, and information about data protection should be added REC should provide support and advice on all consent-related points In addition to individual REC advice, European and national recommendations are given to sponsor/applicant The necessary clarification documents could be archived Sometimes, re-submission should also be required The collection of data, samples, images, etc., could be enabled in crisis situations without consent according to national Infection Protection Law |
Respect for participants | Improved data management Secondary use of only anonymized data at the end of the usually relatively short course of the disease would also make informed consent unnecessary Regarding biobanks, the proposed project could be restricted to COVID-19 and infectious diseases. Additionally, consent to anonymization after the end of the study/use for non-specified research projects should be obtained | |
Independent review | Lack of time/time pressure Co-counselling of the locally responsible REC in case of significantly shortened deadlines for COVID-19 studies Applicants' expectation of rapid feedback Intensive workload Lack of courses/training for PIs due to infection protection measures Frequent emergency staffing of RECs | Better time management Those reviews of proposals on non-COVID-19 topics could be postponed that are required by the National code for physicians In multicentre studies, after several unsuccessful attempts to contact other responsible RECs, assessment should be performed without their involvement In multicentre-studies, additional claims from RECs responsible for secondary research sites are formulated as a suspensive condition Consultation outside the usual deadlines and additional meetings could be conducted while maintaining the usual quality of consultation Prioritization of proposals could be adopted With regard to the investigators’ courses, more tolerance might be necessary, with at least temporary acceptance of online courses Communication with the REC members could be performed via a web-based cloud instead of regular physical jour fixes Communication with applicants could be performed via e-mail and short-term review by chairperson Non-interventional clinical studies could be reviewed with secondary importance. Most of their questions can also be approached slightly later |
Favourable risk–benefit ratio | Uncertainty about the disease In the case of interventional trials, difficulty regarding uncertainty about the disease because there is little preliminary data available or the situation is constantly changing, leading to a necessity for a certain degree of extrapolation Difficulty of assessment due to the heterogeneous clinical picture Limited benefit assessment due to the currently insufficient knowledge about the "natural course" of the disease Amount/frequency of blood samples insufficiently justified | Reduction in the amount/frequency of blood samples For blood tests, consent to use residual blood from routine examination could be obtained (after the patient regains the ability to give consent) |
Fair participant selection | Inclusion and allocation criteria Unclear rationales for the exclusion of certain COVID-19 patient groups Planning of several clinical studies despite the limited availability of hospitalized COVID-19 patients: How to allocate patients? Based on what criteria? Vulnerable populations Increasing number of studies exclusively with clinical and nursing staff | Protection of vulnerable populations Statements on the careful handling of particularly vulnerable occupational groups in this critical situation could be made |