Whilst pandemics are thankfully not common; COVID-19 has brought with it a profound global impact. By June 2020, global deaths had reached 420,000 whilst over 7.5 million people had been infected.
As increased optimism surrounded the control of the virus, the impact on life is still to be fully understood. Some forecasts predict grim long-term societal and financial consequences, across several countries.
Whilst the tragic loss of life and the impact on the quality of life should not be overlooked, there are positives to come out of this crisis.
This article will outline the impact on clinical trials and drug and diagnostic development. However, many parallels with everyday life can be taken into consideration.
Strength through adversity is a commonly used aphorism and one which is true of people and industries alike. When confronted with challenges, human inventiveness knows no limits and COVID-19 has been both the mother of innovation but also the catalyst for the widespread adoption of current technologies.
Thus, it is of little surprise that the clinical trial market has swiftly adjusted to the new paradigm circumscribed by restrictions on social interaction, by looking to leverage technological solutions.
Before proceeding, it is necessary to understand that clinical trials were far from perfect. This has been understood for a long time and the financial imperatives of this inefficiency motivated the industry when reevaluating the approach.
This has come into practice over the last decade, with a key emphasis on the patient as the center of the trial. Whilst a platitude that a clinical trial is not possible without the patients, the approach that research should be developed around the patients, often as individuals, is now being routinely incorporated into studies.
Participation in clinical trials remains low, with the US leading the way, with 5.4% as of 2016 (Statista); yet, beyond the borders of the UK, Germany, France, Spain and Italy, only South Korea has a rate of more than 2% worldwide.
There are many complex reasons behind this, often culturally defined or idiosyncratic; however, they typically originate from the burden of participation, awareness and social/moral compulsions.
The first point is the key and bringing the studies to patients will form the cornerstone of research in the future; by merging digital health technologies with point-of-care testing and progressive supply chains.
With the world needing heroes, frontline workers across the world rose to the challenge, with a large number directly placing themselves in clear and present danger. Simultaneously, the situation presented a degree of redemption for the pharmaceutical industry which is usually vilified.
For those working within the industry at large, their key roles in developing new vaccines, therapeutics and diagnostics now held the greatest prominence, urgency and clarity of need. This brought about unprecedented collaboration between competitors, regulators and academia to help unravel the crisis.
These new partnerships have the potential to revolutionize the way that medicine is developed in the future. The hope is that the present situation leads to a greater emphasis and commitment to human health.
Recent events have only reinforced the frailty of our existence as well as a collective responsibility to help one another.
On top of vaccine delivery, antiviral medication to alleviate the impact of infection is also in development and repurposing existing treatments means that this is within reach. Like the global economy, clinical trials continually face significant disruption as research professionals seek to deal with unknown challenges.
Previous processes had to be quickly revisited as worldwide governments instigated the necessary measures to ‘flatten the curve’ and restrict the number and rise of COVID-19 cases.
Besides restrictions due to strained supply chains, regional limitations and even company restrictions, hundreds of clinical trials were considerably affected with the global average of patients entering studies year-on-year seeing a -79% reduction (Medidata COVID-19 Report v.5).
Whilst expected, there is no guarantee when another pandemic will hit again or what the impact would look like.
Taking what has been learned from COVID-19, it is believed that we can build on this opportunity to identify pioneering alternatives when setting new standards that enable quick, dynamic responses with flexibility and pragmatism.
The industry has been previously slow to embrace new technology, with EDC taking decades to become established. The adoption curve for virtual and digital trials will hopefully be greatly accelerated by the pandemic.
Pre-COVID-19 vs post-COVID-19 – clinical trial challenges revealed
Whilst the industry continues to focus on the development of vaccines and therapies in response to COVID-19, the crisis has had a considerable impact on clinical trials in other therapy areas, particularly on cardiovascular, dermatology and metabolic.
Even though significant regulatory agencies, such as the FDA and EMEA, have promoted guidelines and measures for maintaining the integrity of the trials that attempt to guarantee the rights, safety and wellbeing of patients and healthcare staff during this COVID-19 pandemic, maintaining clinical trials and keeping them on track has been severely challenging.
The COVID-19 pandemic has clearly changed the world and the consequences on the conduct of clinical trials are manifold, including, but not limited to:
Concerns about the safety of patients as well as with the reallocation and hence lack of staff or resources to house these patients have resulted in a reduction and/or delayed enrollment of patients.
Disrupted supply chain due to closed borders, also affecting shipment of clinical trial samples to be tested by a central laboratory
Extension of the duration of the trial, as the study was either slowed down or interrupted during recruitment
New study initiations were placed on hold by either the industry itself or forced by regional lockdowns, which prevented patients from entering trials and visiting hospitals.
Overstretched hospitals, resources and systems
Conversion of physical visits into virtual visits
Recruited patients having to leave the trial
Reprioritization of new test applications to only those that treat, diagnose or prevent COVID-19; clinics allowing only these essential or critical visits and refusing to take part in trials
Risks of compromised data integrity if new procedures are deviating from the original plan
Vendors and contractors unable to meet distribution obligations, such as delivering drugs to sites
There is a clear need to limit patient risks and to support their inclusion into clinical studies. Innovation, flexibility and appropriate use of existing, available technology will be of considerable importance to adjust to this new paradigm.
Beyond COVID-19, sponsors will be looking to greatly expedite patient recruitment and enrollment to catch up with lost time. Looking to the future, overcoming the following challenges are crucial for turning future clinical trials into a success:
Be flexible and accelerate study start-up
Have a clear view and understanding of the evolving situation
Reconsider standard trial design and setup to facilitate data capture
Above all, maintain quality and supply chain.
Cerba Research understands the sensitivity of a highly dynamic and region-dependent situation. Cerba integrates solutions to address each of the challenges, from offering insights into metrics and trends to virtual and agile solutions and centralized data.
While a remote workforce and disjointed operations have become the new normal, Cerba has taken the first steps to get business back to normal and is building beyond standard to remain agile and resilient.
Labs are overwhelmed with a multitude of assays for identifying COVID-19
When encountering the clinical trial space, it is imperative to ensure that inclusion/exclusion criteria are well defined as they establish the framework for patient enrollment.
Given the current worldwide prevalence, sponsors must consider routine inclusion of COVID-19 testing throughout the screening process to eliminate positive patients during the trial.
Since the pandemic began, several tests have appeared on the market, which either detects the presence of the virus or the antibodies against the virus. Both PCR and serology tests are now increasingly available as labs continue to scale up their capacities.
With a wide range of assays available, a large number approved by FDA and other regulatory bodies, the question remains; which test will be the best to include in a study?
The sensitivity, reliability and specificity of tests are not always clearly marked, readily determinable or well-documented. For this reason, Cerba’s scientists have conducted a comparative study for various assays and technologies and have generated a list of tests which meet a certain set of minimum criteria.
Observing the differences in the respective Sars-CoV-2 gene and the present mutations on different continents, it is necessary to devise a sequencing approach.
It is crucial to note that the categorization of cases is a surveillance tool that can be utilized to better understand the burden of the disease, in addition to finding the optimal treatment for a specific individual.
As the current understanding of the virus increases, the use of current tests will evolve and newer tests will become available.
Technology and decentralization as an alternative
The outlook of clinical trials continues to evolve, and next to scientific discoveries, the COVID-19 pandemic has exposed an urgent need for clinical trials driven by next-generation technology.
Departing from protocols highlights the risks of missing or delaying data acquisition from ongoing studies. This underscores the rising value of digital medicine, supported by developments in cloud, mobile and IoT technologies.
Virtual trials are revealing a remarkable opportunity for pharma and healthcare, taking clinical trial management to another level. It is anticipated that digital healthcare and virtual trials will become more common as part of the new ‘normal’ beyond COVID-19.
There are many benefits to virtual trials, both in the short- and long-term, although both also present limitations.
Remote patient monitoring affords participants the freedom and the peace of mind they won’t be exposed to unnecessary risks. Virtual visits enable the inclusion of a larger population of patients and will enhance patient recruitment, engagement and retention.
With the clinical trial ecosystem flipped on its heads, the embrace of virtual technology has offered the best hope for success in transforming the shape of how to perform appropriate clinical trials in the future.
In addition to the move towards digital technology, another solution to the challenges faced today includes employing decentralized clinical trials, protecting both patients and medical staff.
The FDA released guidance back in March 2020 recommending alternative methods when traveling to sites is severely restricted, thus supporting the implementation of decentralization.
For a few years, some CROs as well as technology and software companies have been evaluating this avenue of patient-centric options. The COVID-19 pandemic has now set the stage for virtual and hybrid trials to become more widely accepted and perhaps eventually become the new normal.
Post-COVID-19: the future is now
We are witnessing a very real change in the clinical trial process and at an unprecedented rate. For the last ten years, whilst some solutions were considered to be too risky, the risk of not incorporating them as soon as possible has become greater.
Evolution in this industry is a matter of survival, and many of the modifications that took place during the COVID-19 pandemic will last and be for the better.
Case study – speed and efficiency were of the essence
Cerba Research was approached by the Belgian government to contribute to a government-led consortium.
Collaborating with a large team of pharmaceutical companies, laboratories, software providers, CROs and research institutes, Cerba Research developed an approach for the acquisition and integration of data, aggregating and correlating it into concentrated dashboards, and establishing a framework to make appropriate operational decisions.
After establishing the initial framework and dashboard within just one week, Cerba continually supported the task force’s operational and scientific teams daily.
Led by the Federal Minister, the members of the task force worked (and are still working) to enhance testing against COVID-19, a crucial factor in helping flatten the curve and tackle any further spread of the virus.
Cerba Research, the clinical trial & research division, with its headquarters in Ghent, Belgium, is supplying the logistical support and organization for this project, playing a key role in the delivery of patient samples to academia and pharma for COVID-19 testing.
Ability to adapt quickly to daily changes made and source new supplies as necessary
Successful set up within one week, including the production of a new database
Sourcing materials in-house for shipments on time despite ongoing logistical challenges
Contingency planning and Cerba Research’s flexibility to execute and communicate quickly and effectively allowed the company to meet all timelines.
Risk identification and challenge mitigations proved profitable as the team was well prepared and demonstrated a nimble and committed mindset towards this project.
About Cerba Research
For over 35 years, Cerba Research has been setting the industry standard for exemplary clinical trial conduct. Today, across five continents, with a focus on precision medicine, we are changing the paradigm of the central lab’s role in complex clinical research.
From protocol inception through development and to market, our passionate experts deliver the highest quality specialized and personalized laboratory and diagnostic solutions. Partner with us for the most efficient strategy to actualize your biotech and pharmaceutical products sooner and improve the lives of patients worldwide.
Trial resumptions slowing due to new Covid-19 strains
Since early March 2020, more than 500 companies have publicly announced disruptions to their planned and ongoing clinical trials due to the COVID-19 pandemic. Many companies have delayed the initiation of planned trials or withdrawn them completely, and others have suspended enrollment in their ongoing trials or terminated the trials altogether.
The majority of trial disruptions can be attributed to patient safety measures, strict lockdown requirements, social distancing procedures, and the high demand on medical professionals to treat COVID-19 patients. As the initial peak of the virus started declining, many trials were set to resume activity. However, the number of confirmed COVID-19 cases is increasing again globally, especially in Western areas such as the US and Europe. The news of two more infectious variants of COVID-19 has led to increased restrictive measures globally. The COVID-19 Dashboard on GlobalData’s Pharma Intelligence Center dynamically tracks both disrupted and resumed trials. As of January 25, 2021, 929 disrupted trials have resumed. Out of these trials, 71.9% are currently recruiting participants, 12.8% have completed recruitment but are still ongoing, and 0.5% of trials have yet to start recruiting subjects. The figure below shows that there is a very slight, steady increase of trials resuming activity. Initially, the general trend showed a gradual increase in the overall percentage of trials for each trial status, the biggest of which has been seen in ongoing, recruiting trials and ongoing, not recruiting trials. However, between December 23 and January 25, ongoing, recruiting trials decreased from 74.6% to 71.9%, and completed trials increased from 10.6% to 12.8%. The US has the highest number of resumed trials at 87.5%, followed by the UK at 10.8%, Spain at 9.0 %, France at 8.8%, and Germany at 8.1%. Both new variants of the COVID-19 strain from the UK and South Africa have been shown to be more infectious, causing widespread worry and thus extra precautionary measures such as restricted travel and local lockdown measures. With the global rollout of three main COVID-19 vaccines from Pfizer/BioNTech, Oxford/AstraZeneca, and Moderna, it is expected that global figures for COVID-19 cases could decrease in upcoming months. If this occurs, then the potential of disrupted trials resuming could be likely.