Clinical Researcher—August 2020 (Volume 34, Issue 7)

SPECIAL FEATURE

Achenyo Ochuma, MSc

 

The emergence of the COVID-19 pandemic has resulted in a significant impact globally across various sectors and industries leading to a rapid shift in adapting processes and systems. The nature of COVID-19 is an infectious disease characterized as a respiratory illness associated to other severe symptoms affecting individuals in varying degrees. Following a statement by the World Health Organization (WHO) on January 30, 2020 declaring the outbreak as a Public Health Emergency of International Concern, it has become an ongoing global health priority. Undoubtedly, this directly has an impact on the pharmaceutical and healthcare industries. This article provides an overview of this crisis from the perspective of how clinical trials and activities in the research environment are being managed.

Background

Around the world, various organizations, authorities, and agencies are assessing the impact and providing guidance to enable management of clinical trials and research in the midst of the unprecedented healthcare situation presented by COVID-19. The key authorities include the United Kingdom’s Medicines and Healthcare Products Regulatory Agency (MHRA), the European Medicines Agency (EMA), and U.S. Food and Drug Administration (FDA).

Considerations have been taken for ongoing clinical trials around existing policies and procedures that have to be modified. The overall impact on sponsors, contract research organizations (CROs), sites, and participants depend on several factors and the status of trials. Steps which are critical to determining the impact involve processes covering risk assessments, action plans, and revised agreements between the parties involved.

The global crisis has highlighted the importance of a collective effort in the management of clinical trials. As covered in the following sections, this requires looking at the challenges from the perspective of various aspects of the clinical research landscape, ranging from operational to regulatory issues.

Sponsors

The results from a recent analysis conducted by Medidata show how ongoing research has been affected globally by the pandemic in terms of active studies at sites. A significant decline in the entry of new patients into studies in active recruitment was noted, starting in China in February 2020. Similar trends were noticed across the U.S. and European Union (EU)starting around March 2020.{1}

It is crucial for sponsors to have detailed reporting and analytics in real time in order to adequately assess the impact on trials at a patient, site, and country level to effectively mitigate risks. In April 2020, several large pharmaceutical and smaller biotech companies announced modification of their research and development plans in the form of either temporary delay in site activation or patient recruitment in some trials.{2}

Broadly speaking the challenges being addressed by sponsors cover a combination of:

• Overall oversight on trials status, timelines, and risk management
• Action plans for evaluating continuation of studies
• Protocol deviations
• Safety of participants
• Data quality
• Supply, distribution, and logistics of investigational medicinal products
• Monitoring and audits

Sites and CROs

In response to the pandemic, the Association of Clinical Research Organizations (ACRO) released recommendations for oversight and monitoring of trials that cover the activities of sites, sponsors, and other organizations. The aims are for interim emergency measures to be in place during the ongoing health crisis period. The overview consists of considerations for general oversight, interim measures documentation; routine monitoring resumption, and database lock.{3}

From the perspective of sites, impacts relating to the above considerations will be determined by a decline in the recruitment or screening process leading to delayed start-up of studies or ultimately halted studies. Changes to how site visits by patients are handled therefore are necessitating utilization of remote access tools in many cases. Modification of study models will enhance capability for specific diagnostic testing required for each study. This implies an additional administrative burden in order to accommodate these and other changes.

For ongoing studies, the issue of informed consent must be addressed in terms of how it will be captured, based on the format of informed consent forms. Meanwhile, monitoring the storage conditions of the investigational medicinal product (IMP) is essential, and is just one aspect of monitoring research subjects’ safety and the efficacy and credibility of data during a trial. The severity of the impacts on each study will vary depending on the phase of the trial.

On a broader level, the role of CROs in managing the impact depends on proactive decisions made through cross functional working at all levels to control resources internally. Partnerships with vendors externally form part of the dialogue in order to ensure that all areas are efficiently managed, including supply chain and logistics.

The establishment of expert committees or task forces within organizations to focus on implementing action plans for addressing this health crisis and others like it will streamline the necessary activities, and may involve upskilling or repurposing members’ expertise to meet the new demands. The review of objectives, milestones, and goals will be incorporated as a result. In maintaining modified processes, a focus on patient safety as well as on the safety of study teams is essential.

Remote site support services, electronic reporting systems, safety monitoring, and laboratory testing are other areas that also need to be included in the decision-making process.

Supply Chain and Logistics

We can expect a knock on effect and long-term impact from the pandemic on supply chains from manufacturing to distribution, which includes active pharmaceutical ingredients (APIs) and IMPs. Clinical trials have been disrupted due to implications from additional measures such as lockdown, quarantine, and social distancing implemented across the world. Transportation limitations which have arisen increase the demand on other delivery services. The potential issues spinning off from these trends require frequent evaluation as the situation evolves. It is significant to note that regulatory requirements related to these challenges vary in different countries, but are time consuming in any event, and that regulators are setting in place support systems to enhance the stability of the supply chain.

Adaptation of Trials

An article published in the Drug Information Association (DIA) Global Forum in May 2020 examines recent dramatic changes in clinical trial operations as the adoption of virtual trials accelerates. This model is based on decentralised trials, whereby patient safety and data quality are maintained, and the platform is run from a mobile device coordinating all study-related procedures to be accessed by eligible participants. The technology allows the network of doctors, nurses, researchers, and data managers to be combined with the platform.

The adoption of such trials has been gradual in the past five years, and the pandemic has created an opportunity where this model could be embraced as the clinical trial landscape changes. The FDA and EMA have published guidance on the use of virtual visits to ensure the continuity of trials.{4}

Regulatory Guidance

The World Health Organization (WHO) has developed a database of literature for technical guidance and global research regarding the coronavirus. WHO has an important role in setting priorities for research and for coordinating and facilitating trials. A recent article in The Lancet on the global coalition highlights the launch of the SOLIDARITY trial studying potential treatments for COVID-19 by reviewing the evidence used to generate COVID-19 study guidelines.{5}

Regulatory agencies have issued various guidance documents with regular updates, as outlined below, to enable sponsors and sites to manage the conduct of clinical trials during the pandemic:

• UK MHRA developed a guidance to support disrupted clinical trials, including ongoing, resumed, and new studies. The guidance highlights flexibility of requirements for these trials, ensuring that the priority should be the safety of participants. Alongside this, the National Institute for Health Research (NIHR) set out a framework in May 2020 to restart paused research activities.{6} The Health Research Authority in the UK also provided guidance for amendments made to existing studies for research conducted by the National Health Service, covering a range of scenarios with oversight to protect participants.
• FDA guidance provides general considerations to assist sponsors based on ongoing trials, existing policies, and trials impacted by the public health emergency. A question and answer section is featured to address a range of related issues.{7}
• EMA guidance aims to assist implementation of protocol deviations with advice specific to new trials initiated for potential COVID-19 treatments, according to trial methodology suggestions issued by EMA’s Human Medicines Committee.{8}

The lessons derived from the impact of COVID-19 on research activities show that collaboration between pharmaceutical companies, healthcare industries, CROs, patient associations, and regulatory authorities is vital for data integrity and quality of research to be maintained. There are various recommendations to address the considerations taken into account for the broader perspective of the clinical trials landscape. Identifying best practices for trials based on regulatory guidance will shape the future of what research would look like.

References

1. COVID-19 and clinical trials: the Medidata perspective. Medidata Solutions. https://www.medidata.com/wp-content/uploads/2020/03/COVID19-Clinical-Trials_20200324-1.pdf
2. COVID-19 and clinical trials: the Medidata perspective. Medidata Solutions. https://www.medidata.com/wp-content/uploads/2020/04/COVID19-Clinical-Trials_20200408.pdf
3. The Association of Clinical Research Organizations. 2020. ACRO’s considerations on monitoring during COVID-19.https://www.acrohealth.org/acro-considerations-on-monitoring-during-covid-19/
4. Cotliar, J. 2020. How a pandemic accelerated the adoption of virtual trials. DIA Global Forum. https://globalforum.diaglobal.org/issue/may-2020/how-a-pandemic-accelerated-the-adoption-of-virtual-trials/?_ga=2.171696800.1021148269.1590665968-819058252.1586959045
5. COVID-19 Clinical Research Coalition. 2020. Global coalition to accelerate COVID-19 clinical research in resource-limited settings. The Lancet https://doi.org/10.1016/S0140-6736(20)30798-4
6. Medicines and Healthcare Products Regulatory Agency. 2020. Managing clinical trials during Coronavirus (COVID-19). https://www.gov.uk/guidance/managing-clinical-trials-during-coronavirus-covid-19
7. Center for Drug Evaluation and Research. 2020. FDA guidance on conduct of clinical trials of medical products during COVID-19 public health emergency. U.S. Food and Drug Administration. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/fda-guidance-conduct-clinical-trials-medical-products-during-covid-19-public-health-emergency
8. European Medicines Agency. 2020. Guidance on the management of clinical trials during the COVID-19 (coronavirus) pandemic. https://ec.europa.eu/health/sites/health/files/files/eudralex/vol-10/guidanceclinicaltrials_covid19_en.pdf

Achenyo Ochuma, MSc, is a Pharmaceutical and Healthcare Researcher and Independent Consultant in the United Kingdom. She contributed this article through Kolabtree.