FAQ - COVID-19 studies
The European Medicines Agency (EMA), the GCP Inspectors Working Group (GCP IWG), the Clinical Trials Facilitation Group (CTFG), the Clinical Trials Experts Group (CTEG) and the European Commission (EC) have jointly developed a list of recommendations to mitigate the negative impact of the COVID 19 pandemic on the conduct of clinical trials.
Sponsors and investigators must take into account that these recommendations are supplemented by national laws and guidelines that take precedence over these recommendations. However, the present document attempts to adopt most of the practices currently in force in the Member States in order to serve as a harmonised set of recommendations at EU level.
This guidance covers actions that sponsors of ongoing clinical trials affected by the coronavirus disease (COVID-19) pandemic should take to help ensure the integrity of their studies and interpretation of study results while safeguarding the safety of trial participants as a first priority.
This complements the good clinical practice guidance on how sponsors should adjust the management of clinical trials and participants during the COVID-19 pandemic.
Please note that further updates are possible and likely given the rapidly evolving nature of the pandemic.
Also after the update of the recommendations at the European level, Austria is still one of the countries which are critical of remote source data verification (SDV). There is not enough experience with this procedure, and the necessary technical requirements are not yet well established. The primary goal is to ensure quality assurance while respecting data protection and at the same time not placing an additional burden on the trial sites during thepandemic. In addition, access for monitors to trial centres is possible in Austria.
The rules for remote source data comparison are therefore adapted as follows:
Remote SDV is possible for:
- Clinical trials investigating medicinal products for the prevention or treatment of COVID-19 and its sequelae
- Pivotal clinical trials (phase III) investigating medicinal products for treatment or prevention of serious or life-threatening conditions
- Situations where the absence of SDV for critical data may likely pose unacceptable risks to participants’ safety or the reliability/integrity of trial results
The introduction of Remote SDV always requires a substantial amendment to be approved by the BASG. The introduction must already be mentioned in the cover letter.
In addition to the justification for remote SDV and a benefit/risk assessment, the documents mentioned in Annex I of the EU guideline must be submitted in this amendment, including details of the remote SDV process and an agreement by the trial sites. A general reference for introduction as an option is not possible.
Pursuant to Section 11(1) of the COVID 19 Emergency Measures Ordinance, entry into hospitals and nursing homes is limited to the exceptions specified in paragraph 2. In addition to patients, caregivers and visitors, persons who are necessary for the care of patients or the operation of the facility, including auxiliary and administrative staff are allowed.
If clinical studies are in progress at the hospital, visits by monitors are to be regarded as necessary for the operation of the facility, since otherwise the clinical study cannot be monitored and thus the corresponding legal obligation cannot be fulfilled. Access is thus permissible under the COVID-19 Emergency Measures Ordinance.
This applies equally to clinical trials under the Austrian Medicines Act and to clinical investigations and performance evaluations under the Austrian Medical Devices Act.
All urgent measures taken to protect participants or safeguard the trial integrity required by the COVID-19 pandemic should be documented by the sponsor together with a justification and benefit/risk evaluation.
Changes with impact on participant safety or trial integrity ("substantial") should be notified to the Federal Office as an urgent safety notification together with their implementation. A substantial amendment is not required. For a notification only the receipt by the BASG is confirmed. There is not authorisation and no publication on the BASG website.
The notification should be made by e-mail to email@example.com. "COVID-19" and "urgent safety notification" should be included in the subject line. A joint notification for several studies is acceptable as long as they are referenced by EudraCT number in the cover letter.
After the end of the pandemic situation or at the request of the Federal Office, a summary report on all measures taken should be submitted as a single substantial amendment. The only exception are trials for which apart from the halt and restart of recruitment no other safey measures were taken.
As the restrictions imposed by the pandemic are being gradually reduced, the changes reported as an urgent safety measure (Section 37a (4) AMG) (see above) can also be gradually withdrawn by simple notification. No approval or confirmation by the Federal Office is required for such notifications.
After the end of the pandemic situation, before the end of the study or at the request of the Federal Office, a final summary report on all measures taken as aresult of the pandemic situation must be submitted as a one-time substantial amendment. This amendment serves as the formal conclusion of all changes taken as safety measures and their evaluation by the sponsor.
In this report, please describe all amendments, urgent security measures and any other changes (e.g. changes in monitoring). It should be stated whether the measures are maintained or withdrawn. The measures should be evaluated in terms of their success, and the study as a whole should to be evaluated in terms of its integrity.
Only studies for which no measures other than a stop and a restart of recruitment ("recruitment pause") have been taken shall be excluded.
In cases where, for the protection of the trial participants, a continued supply of trial medication needs to be maintained at home and shipment via pharmacies (see BASG FAQ) is not possible, the sponsor may organise for trial medication also to be shipped directly from the trial site to the trial participants via courier. This is only possible provided that the product is suitable for transport and administration at home use. Training on administration at home must have been provided.
The sponsor needs to establish appropriate procedures to ensure the stability and sound condition of the trial medication during transport. The means of transport and transport packages as well as the necessitiy of temperature control must be defined by the sponsor based on quality risk management. The stability of the trial medication, the seasonal environmental temperatures and the duration of transport should be taken into account. Transport and receipt are to be documented accordingly and must be verified by the investigator (e.g. via telephone call or e-mail).
The identities and addresses of the trial participants must not leave the location of the trial site, except with the shipment package to the trial participant (e.g. on the package label, courier slip, shipment letter). Articles 5.14.4, 8.2.15, and 8.3.8 ICH GCP require the sponsor to retain IMP shipping records, but this generally applies only to shipments between the sponsor and trial sites and to shipments between trial sites. It does not apply to direct shipments from trial sites to subjects. Documentation for these direct shipments need only to be maintained at the trial site for traceability. If it is necessary to file copies of such shipping records in the sponsor TMF, e.g., if relevant for protocol deviations or quality issues, the corresponding text passages with personal identifiers (name, address of trial participant) should be redacted before the copies leave the trial site.
Exception: As stated in the current version of the EU Guideline (see above), in exceptional cases where the site is unable to handle the additional burden, the delivery can also be handled by the sponsor via an independent third party. In these cases, a substantial amendment (!) should be submitted to the BASG for each study. In this amendment, the investigator must confirm in writing that all the measures described here, including involvement contract staff by trial site, have been exhausted and shipment from the centre to the participant is still not possible. The other recommendations of the guideline should also be observed.
In case a trial site cannot cope with the additional workload of IMP shipment to trial participants it could be considered to provide additional staff ressources to the trial sites in line with Art. 4.2.5 and 4.2.6 ICH GCP. These could be contracted personnel experienced and skilled in IMP handling which are delegated study medication-related activities (e.g. IMP receipt, stocking the inventory, dispensing, packaging for shipment) by the investigator under his/her responsibility and supervision.
For involvement of contracted staff at trial sites the GCP matters Q&A #11 According to the ICH GCP and applicable EU laws, it is allowed that the sponsor contracts third parties to conduct trial related duties and functions that are clearly the responsibility of the investigator? on the EMA homepage should be considered.
The monitoring strategy should be reassessed by the sponsor if on-site monitoring visits are temporarily not possible or cannot be carried out at investigational sites to the extent planned. Possible changes could include
- Cancellation and/or postponement of already planned on-site monitoring visits
- Extension of the on-site monitoring visit interval
- Conducting telephone and/or video calls instead of on-site monitoring visits
- Centralised monitoring activities via various electronic systems (e.g. eCRF, IXRS, etc.)
Temporary changes in the monitoring strategy should be specified in writing, e.g. in the monitoring plan or an annex to the monitoring plan. Monitoring activities that have been conducted must be documented accordingly and communicated to the sponsor (Article 5.18.6 ICH GCP).
Once the situation has normalised, more on-site monitoring should be conducted to deal with the backlog, the postponed source data verification (SDV) and to address any quality problems.
Audit programs should be reassessed by sponsors with regard to investigational site audits if on-site audits are temporarily not possible or cannot be carried out to the extent planned. Possible changes could include:
- Cancellation and/or postponement of already planned on-site audits
- Carrying out a remote audit (based on telephone and/or video audits and inspection of electronic systems, e.g. eCRF, IVRS and of site-specific documents in the central TMF) if the reduced inspection scope is of sufficient purpose
- Change to investigational sites that are not or less affected by the pandemic, unless these are triggered audits.
Audit activities performed must be documented accordingly (Article 5.19.3 ICH GCP).
Important: For remote source data verification (SDV) the same rules as for monitoring (see section above) apply.