COVID-19: Guidance on conducting clinical trials

Within the life sciences sector, the impact of the novel coronavirus known as COVID-19, has the potential to disrupt new and ongoing clinical trials of various medical products.  To help combat these complications, the European Commission, the European Medicines Agency (EMA) and national Head of Medicines Agencies (HMA) published, on 20 March 2020, new recommendations for clinical trial sponsors on how to manage the conduct of clinical trials in light of the new challenges created by the COVID-19 pandemic.  The Guidance is available here.

The Guidance aims to assist sponsors of clinical studies in the implementation of changes and protocol deviations in conducting research, and in ensuring the rights, safety and wellbeing of subjects. In addition, the Guidance provides specific advice on the initiation of new clinical trials for potential COVID-19 treatments, and in particular on the need for large, multination trial protocols.  This is in line with the call for robust trial methodology in clinical trials for potential COVID-19 treatments or vaccines issued by the EMA’s human medicines committee (CHMP) on 19 March 2020, which can be viewed here.

Due to the urgency, the Guidance is issued without prior public consultation and clinical trial sponsors should note that due to the rapidly evolving situation further updates to the Guidance are possible and likely.  Sponsors and investigators also need to take into account that there might be specific national legislation and guidance in place, which they should consult and which can be used to complement the Guidance, or, with respect to particular matters may take priority over these recommendations.  In that regard, on 23 March 2020 in Ireland, the Health Products Regulatory Authority (HPRA) published national guidelines, which can be viewed here.

The Guidance provides an EU-level harmonised set of specific recommendations to ensure the safety of trial participants as well as the integrity of clinical trials during the COVID-19 pandemic.  Sponsors should consider:

• Conducting a critical assessment as to the feasibility of starting a new clinical trial, or including new trial participants in an ongoing trial.  The ability to confirm eligibility (including written informed consent according to national laws and regulations) and to conduct key safety assessments and trial evaluation is of particular importance; and
• The most appropriate measures during COVID-19, which should generally be agreed with investigators, and could include:
  • Conversion of physical visits into phone or video visits;
  • Postponement or complete cancellation of visits to ensure that only strictly necessary visits are performed at sites; 
    
  • A temporary halt of the trial at some or all trial sites; 
    
  • Suspension or slowing down of recruitment of new trial participants; 
    
  • Extension of the duration of the trial; 
    
  • Postponement of trials or activation of sites that have not yet been initiated;
    
  • Closing of sites; 
  • If unavoidable (it should be justified that this is a truly exceptional situation based on the personal risk-benefit ratio for the individual trial participant), transfer of participants to investigational sites away from risk zones, or closer to their home, to sites already participating in the trial, or new ones could occur; and/or
  • A need for critical laboratory tests, imaging or other diagnostic test to be performed for patient safety.
    

In order to mitigate the negative effects of the COVID-19 pandemic on the conduct of clinical trials, the Guidance stresses that when changes in ongoing trials are considered, the overall well-being and best interests of the participant should also be considered.  Actions should be proportionate, taking into account in particular the legitimate interest of trial sites in avoiding further burden in terms of time and staffing during the COVID-19 pandemic.

The Guidance goes on to address additional areas of concern, such as:

• Risk assessment(s) to be carried out by sponsors of each individual ongoing trial and the investigator of each individual participant, and implement measures which prioritise subject safety and data validity.  The Guidance reaffirms that in the event of conflict, subject safety must always prevail;
  
• Communication with authorities.  Priority will be given to any (new) clinical trial applications for the treatment or prevention of COVID-19 infection and/or substantial amendment applications to existing clinical trials necessary as a result of COVID-19;
  
• Agreement with and communication to sites.  The Guidance emphasises that it is important that changes and local implications are made clear;
  
• Changes to informed consent/necessity of re-consents – bearing in mind the current pressure on the medical profession.  The Guidance emphasises that alternative ways of obtaining informed consent should be considered during the pandemic e.g. contacting the trial participants via phone or video-calls and obtaining oral consents supplemented with email confirmation;
  
• Changes in the distribution of the investigational medicinal product (IMP).  Sponsors must assess the risks relating to the product and consider alternative shipping and storage arrangements to remove avoidable visits to sites and to provide patients with needed treatments.  The Guidance sets out in detail various practical considerations.
  
• Changes to certain sponsor oversight responsibilities such as monitoring and quality assurance activities.  The burden of the introduction of any alternative measures for the site staff and facilities should also be considered in order to strike an acceptable balance between oversight and capacity at the site.
  
• Protocol deviations including the requirement for sponsors to escalate and manage protocol deviations in accordance with standard their procedures and bearing in mind the best interests of participants; and
  
• Reimbursement of exceptional expenses incurred in connection with urgent measures implemented for the protection of participants.  

As the COVID-19 pandemic continues to gain force and have far ranging consequences, it will certainly impact on the operations of research development & innovation institutes, pharmaceutical, biotechnology, and medical device companies, particularly in the context of clinical development activities.  We will continue to monitor the landscape and  provide further updates as the situation evolves.

For further information or advice, please contact Colin Sainsbury or Catherine Dowling in the ByrneWallace Life Sciences Team.  

Please note that the content of this summary does not amount to professional advice. Legal and tax advice should be sought in respect of specific queries. The COVID-19 situation is evolving rapidly and this update is provided on the basis of information available as at 27 March 2020.