Clinical Trial Disruption: Getting Back on Track, Part 2

Prior to the pandemic, the Mexican Health System had already been affected due to political/administrative decisions and there were already fewer human and material resources available for patients. At the start of the health crisis, efforts were fundamentally focused on attacking the COVID-19 problem, while the distribution and availability of treatments for other diseases were placed on hold.

As for health personnel, whether physicians, nurses, or assistants, a great number requested temporary leave due to the pandemic, while others were reassigned to areas where patients with COVID-19 were being treated. This distracted a critical mass of personnel from assisting on clinical trials.

It is also important to mention that the personnel at health institutions have suffered from physical and/or mental exhaustion, or burnout, which implies long working hours that are not carried out under the best conditions. It should be noted that Mexico has been one of the countries where the greatest number of health personnel have suffered from COVID-19 and even more have died. All of this has led to insufficient human resources for the development of trials. Therefore, there is a lack of investigators, sub-investigators and study coordinators to continue clinical trials, let alone starting new trials.

Continuing with the analysis of each of the factors and parts of a clinical study, patients participating in studies are now limited to being enrolled since the vast majority of the hospitals where the protocols are carried out were “converted" to sites where patients with COVID-19 are being treated. On the other hand, the Mexican population in general does not feel safe going to hospitals at the present time, regardless of whether it has been classified as a COVID or non-COVID care center. There is great fear of being infected. It should be noted that, in the development of clinical protocols, the interaction of health professionals with patients is relevant and currently, due to the rules of social distancing, now limited. This has also hindered, among other things, patients from going to their appointments.

‘Infodemia’

No less important is what is called "infodemia," or the "overabundance of information (some truthful and others false) on a subject." Media has been both a deterrent and an asset through the pandemic. Misinformation and fake news have cluttered people’s minds, leading crowds of people to wrong assumptions and to act inadequately when faced with this contagion. Other information has provided precise and exact explanations for people to stay safe and remain as far as possible from possible sources of contamination and infection.

A very valuable tool, but at the same time with certain limitations, has been the use of telemedicine, as well as the remote care of patients. It is important to mention that these tools are not yet in the domain of many sectors of the population nor are they available to all patients or at research sites.

Regarding the facilities where patients are regularly enrolled and treated when partaking in specific clinical trials, these have also been limited. Most hospitals have been changed to COVID-19 facilities and are no longer conducting trials. Likewise, the availability of medical equipment that most often is necessary for the implementation/development of research protocols is now limited due to delayed regulatory processing. It is important to mention that the federal budget cut for the health sector has also had an impact on the supply/availability/storage of medicines, as well as supplies of all kinds.

It is worth highlighting the role played by all those participating in clinical monitoring. At the moment, much of the work has been limited to teleworking, which limits the access to the actual source of the information.

Starting from the fact that all the information in a research protocol must be documented and all the evidence of the evolution of a clinical study should be protected, the situation of the pandemic has created a challenge to carry out essential additional steps for adequately recording and saving information on patients.

Most of the available resources have been focused on treating COVID-19, as well as developing vaccines to combat this disease. We know that the creation of vaccines against COVID-19 has broken the paradigm of the time required for development, since the whole process was accelerated; otherwise, it would have taken up to 15 years to create a vaccine against the new coronavirus. Even drug development has been altered. New drugs are now being tested to treat COVID-19.

It is also worth noting that both the importation of supplies and medicines, as well as travel restrictions have had an impact on the development of clinical studies.

On Aug. 27, 2020, the US National Library of Medicine through Clinical Trials.gov reported 2,757 clinical studies related to COVID-19, 59 of them in Mexico. Today, Clinicaltrials.gov reports there are 6,884 trials related to COVID worldwide, 172 in Mexico. This highlights the importance this topic has had on clinical research and how it has overturned trials on a specific topic.

On a positive note, major pharmaceutical companies are working together with the Mexican government for the production of a vaccine against COVID-19. This vaccine expects to receive the endorsement of the US regulatory authority, the FDA, to later be endorsed by COFEPRIS and to be able to start administering it to the population very soon.

Having said the above, we must not forget a relevant point in this whole context, which is the patient protection, since the safety and well-being of the participants in the clinical trial must be guaranteed and preserved.

Here we will highlight the following: the Declaration of Helsinki and the Oviedo Convention state that “the well-being of the human being must prevail over the interest of society and science, haste cannot justify a decline in methodological rigor, it is better to have the uncertainty of ignorance than to have poor quality conclusions,” indicated Dr. Rosa María Wong Chew during her conference transmitted by Facebook Live at the Faculty of Medicine on May 22, 2020, as head of the Clinical Branch of the Research Division of the UNAM School of Medicine.

In terms of obtaining results, one must consider the implications of this situation, which includes the lack of the collection of real treatment effects for studies with little statistical power, or the misstatement of an effective treatment based on a surrogate endpoint.

It should not be forgotten that investigative protocols not related to COVID-19 have been somewhat delayed or suspended, or have had to be adjusted to the current circumstances. No less important, has been the pharmacovigilance that has been limited on other treatments.

Most of the investment in COVID-19 to date has been new funding, that is, not at the expense of the current healthcare budget, although possibly at the expense of the national economy or specific expenditure undertaken by the pharmaceutical firms.

Venture capital financing can be difficult to secure, adding challenges for the life sciences sector in bringing new innovations to market.

Conclusions

The new implementation/development of clinical studies worldwide should contemplate a redesign in the interaction of the research team and an update of plans.

It must be considered that this pandemic is here to stay for an uncertain period of time, so we will most likely not return to the way we used to work/interact in the near future. From now on, we must consider remote communication and the use of technological tools that will allow us to maintain strict control of the studies without putting the health of both the patient and personnel who interact with them at risk.

Corporate resilience will be a fundamental factor for overcoming and surviving the pandemic in the best way possible.