The pandemic lockdown and quarantine has slowed down or in some cases paused most of our everyday lives. With daily routines affected, there is a butterfly the effect that ended up affecting most professions in some or the other way- including the clinical research industry.
With the whole world focusing on COVID19 research, much of non-COVID19 related ongoing and upcoming projects have taken a backseat – especially, in-person operations. This doesn’t necessarily mean a complete halt in the research process, regulatory bodies like USFDA have issued guidelines on conduct of clinical trials during COVID-19 pandemic. Although these guidelines are designed to tackle current pandemic, these changes are bound to have short term implications that could potentially shift the way in which the industry functions in the long term.
Effects on research operations/procedures/ trial progress:
Trial sites that have been transformed or dedicated for COVID-19 treatment may not be capable of recruiting or conducting future trials. At the same time, the recruitment and conduct of ongoing trials have taken a significant hit with most of the investigators and healthcare personnel catering to COVID patients and pandemic. Especially in our country where the patient to doctor ratio is high enough in general circumstances, doctors involved in trials might have to shift their focus on providing COVID related services and their availability at trial site might be irregular.
Transport restrictions during lockdown have disrupted supply chain of investigational products since the investigational products cannot reach the trial site, products under manufacture are on hold due to non-functional or dysfunctional manufacturing units and unavailable labor. Moreover, global trials might face delays in product delivery since most countries have closed their borders for international travel, import and export.
In the early stages of the pandemic, the question was of taking critical decisions on withholding or postponing trials in the recruitment or pre-recruitment stage for trial sponsors. A significant impact of lockdown can be observed on global trials with respect to difference in trial conduct due to varied pandemic related restrictions like some countries are able to conduct trials as per schedule, while others are not able to.
So far, the regulatory bodies including CDSCO have issued guidelines with respect to the challenges in trial conduct for continuity and progress of ongoing trials. These guidelines mandate sponsors and CROs to take necessary actions such as protocol deviations while prioritizing patient safety and data integrity.
However, several ethics committees or review boards might be temporarily non-operational due to lockdown restrictions which could pose as a considerable hurdle for obtaining regulatory clearances and approving the mandated amendments for ongoing or upcoming trials. This is a major challenge since a protocol deviation would require the sponsor/CRO, regulatory authorities and ethics committees to coordinate. As companies learn to adapt and consider implementing new strategies to keep clinical trials on track, in many cases the only option is to temporarily pause or delay development programs.
Effects on trial participants:
Trials with the following population would face most of the challenges because of the pandemic: –
- enrolled populations, including the elderly, the immunocompromised, and patients with pulmonary conditions (e.g., COPD)
- Have primary or secondary endpoints that require in-person visits or hospital infrastructure and equipment (e.g., CT and PET scans) for assessment.
- Trials that require in-person screening.
- Involve indications with minor safety or quality of life implications for patients (e.g., “lifestyle drugs”) and indications where a patient’s environment has a significant impact on therapeutic success (e.g., psychiatric and neurological indications)
- Are currently in the patient recruitment stage or are in Phase 1 with healthy participants
- An infection in the participants may affect the outcomes of the study and in some cases, some participants may need to be withdrawn from the trial.
These consequences could be especially devastating for trials in rare diseases, where available patient population is very small.
Effect on companies /research organizations:
Delays in projected launch timelines could occur as a result of delayed clinicaltrials. This may in turn lead to shorter time period of patent validity and lower near-term revenue forecasts. Changes in launch timelines have the potential to alter competitive scenarios in many therapeutic areas and other facets of the industry, where in the opportunities are up for grabs for whoever adapts and responds to pandemic related changes exceptionally.
Companies, especially small scale, have to adapt to renewed guidelines and switch to operating remotely, or re-evaluate efficiency of current mode of operations, while following the prescribed regulatory measures. This in turn could be a significant problem for those who weren’t adept with appropriate resources in order to make necessary transitions in their mode of operations. The impending economic crisis would only weigh into this un-resourcefulness. This is particularly challenging for countries (like in Europe) where legalities such as General Data Protection Regulation (GDPR) could obstruct the remote functioning of trials.
Pricing negotiations also could be impacted by the pandemic, especially for some non-COVID-19 therapies (e.g., the third or later drug to market in a class) which are perceived to be of low unmet need. New recruitments into companies be on hold due to postponed graduations and current workforce might take a hit because of economical setbacks that could ultimately effect company productivity.
Like any other industry Clinical research industry should come up with some solutions to fix the problems associated with COVID-19 pandemic. The obvious solutions recommended are decentralizing and partnering. For example, home visits, shipping investigational products to participant’s residence, sample collection from home or nearby pharmacies can help performing a clinical trial even in lockdown. Instead of halting, it is time to resume the clinical operations but close monitoring of situations and safety of research staff should remain a priority.