While sponsors of clinical trials frequently face legal and practical challenges, the current situation is unparalleled in its global reach, potentially affecting the majority of, or all, trial sites. As mentioned in our previous Update, regulatory authorities issued guidance to help sponsors manage their ongoing trials during the COVID-19 pandemic. Based on these guidelines, below are some practical issues that most sponsors will face and some considerations on how to address them.
As mentioned in our previous Update, most regulatory authorities highlight that sponsors’ risk assessment is critical.
The guidance issued jointly by the European Commission, the European Medicines Agency (EMA) and Heads of Medicines Agencies (HMA) for sponsors on how to manage the conduct of clinical trials in the context of COVID-19 (EMA Guidance) provides, inter alia, that the “risks of involvement in the trial, in particular with added challenges due to COVID-19, should be weighed against anticipated benefit for the participant and society.”
Further, Guidance to Industry from the U.S. Food and Drug Administration (FDA) emphasizes that sponsors deciding whether to continue administration of an investigational product during the pandemic should “carefully consider context-dependent issues.” These issues include whether a trial participant appears to benefit from the treatment, the seriousness of the disease or condition treated with the investigational product, whether there are reasonable alternative treatments and the risks involved in switching to an alternative treatments if necessary. It is advised that the risk-benefit section of the protocol address any additional risks caused to participants by the COVID 19 circumstances along with risk mitigation measures.
When conducting their risk assessment, sponsors should, further, anticipate as many issues as possible before they materialize, in particular shortages or trial sites’ becoming unavailable, so as to consider relevant potential issues and possible mitigating measures.
At the time of writing, many sponsors will likely already have assessed their studies and carried out changes that are immediately required (see our previous Update on changes to your trial). Sponsors will need to continue reassessing their studies in light of changes in local conditions that will arise in the days, weeks and potentially months ahead. In addition, sponsors will need to work closely with regulatory authorities and Ethics Committees (ECs)/Institutional Review Boards (IRBs) if possible.
Patient Visits to Sites
As highlighted by the various guidelines, access to sites can be challenging — or even impossible — because patients may be in quarantine, the sites may not have enough capacity to take care of them or patients are advised not to come to the site. Providing trial patients with study drugs, supporting patients who experience adverse events and collecting information about these events may become very challenging in these circumstances.
Delivery of Study Drugs to Patients
Sponsors may consider various options to continue providing the study drug to patients who have difficulties accessing their trial site. These alternative options, and their applicability depending on the specific trial and circumstances, may include
- sending the study drug directly to patients from the sponsor or the site if permissible in the relevant country; for example, the UK’s Medicines and Healthcare products Regulatory Agency (MHRA Guidance) explained in its guidance in which circumstances it may be appropriate to post study drugs to trial subjects (see Sidley Update)
- providing patients with additional quantities of the study drug to reduce their visits to the site as much as possible
- transferring patients to alternative sites where possible and feasible
- temporarily halting the trial
The suitability of each option for a specific trial or patient will depend on a case-by-case assessment taking into account, among other things, the study drug, including route of administration; the patient; and other drugs provided as part of the study. Sponsors may need to consider alternative methods of monitoring trial participants who no longer have access to the investigational product or to the investigational site.
The delivery of the study drug may furthermore come into jeopardy because the COVID-19 pandemic is causing problems in almost all links in the supply chain, including the manufacture of active pharmaceutical ingredients as well as distribution channels. Sponsors should assess the risk of urgent shortages of the study drug at some sites and whether sites are still able to handle and control the delivery of the study drug to patients’ sponsors.
Sponsor should also ensure that any redistribution follows established procedures and may require the involvement of a qualified person or the person responsible for distribution of the study drug.
Patient Safety and Adverse Event Reporting
Adverse event reporting is key to ensuring the safety of patients during the trial. However, the additional workload and strain on existing resources caused by COVID-19 will in many circumstances result in investigators’ not being available at the same rate as originally anticipated to address adverse events or to collect and forward adverse event information to the sponsor. Sponsors should therefore consider whether alternative methods for safety assessments could be implemented and would be sufficient to ensure the safety of participants. For example, FDA guidance allows sponsors to consider virtual clinical trial visits or assessments rather than on-site visits.
For clinical trials subject to FDA regulation, those changes to the study protocol can be immediately implemented but must be subsequently reviewed and approved by the IRB, and notification must be provided to FDA.
Sponsors’ monitoring of outsourced activities is typically an area of scrutiny by regulators. However, most regulatory authorities recognize in their respective COVID-19 guidelines that certain changes to the usual oversight are permissible. For example, temporary and alternative proportionate-to-risk mechanisms of oversight might be required.
Sponsors should, however, consider planning for robust follow-up measures when the situation is normalized, for example, increased on-site monitoring for a period that is sufficient to ensure that the effect of the altered monitoring has been established and mitigated.
From a data privacy perspective, there has been a large volume of guidance published by the European Data Protection Board, the European Data Protection Supervisor and various U.S. regulators and national data protection authorities in the EU and the UK.
One key concern is in relation to information security by virtue of increased remote working, scams and phishing attacks and weakened information governance controls. This is particularly relevant for sponsors given the sensitivity of the personal data being processed on their behalf by contract research organizations, laboratories and other processors. To counteract these increased risks, EU and U.S. regulators and law enforcement agencies are recommending that organizations adopt additional measures to ensure sufficient cybersecurity protections. These include conducting a cybersecurity vulnerability review to consider the organization’s exposure to specific COVID-19 related cyber risks.
Separately, in relation to ongoing communications with clinical trial stakeholders in the EU, sponsors will need to determine whether the communications being sent would fall within the scope of the e-Privacy Directive’s requirements as constituting unsolicited electronic direct marketing and, in turn, require consent. Likewise, for U.S. purposes, sponsors will need to determine whether email or text communications may raise concerns with the Controlling the Assault of Nonsolicited Pornographic and Marketing Act, the Telephone Consumer Protection Act or other applicable requirements.
Sponsors may also need to consider the adequacy of existing privacy notices where, for example, additional personal data are being collected and/or new means of collection are being implemented. We would recommend developing a COVID-19 privacy protocol that adequately addresses what personal data can and cannot be collected, how and when this data should and should not be collected, used or shared, the enterprisewide security measures in place to protect the data in transit and at rest and how long such data should be retained.
Sidley Austin LLP provides this information as a service to clients and other friends for educational purposes only. It should not be construed or relied on as legal advice or to create a lawyer-client relationship.
Attorney Advertising - For purposes of compliance with New York State Bar rules, our headquarters are Sidley Austin LLP, 787 Seventh Avenue, New York, NY 10019, 212.839.5300; One South Dearborn, Chicago, IL 60603, 312.853.7000; and 1501 K Street, N.W., Washington, D.C. 20005, 202.736.8000.