Applied Clinical Trials
Europe may not be yet be winning huge praise for its response to the COVID-19 pandemic-but the EMA is coming out of it with flying colors.
Europe may not be yet be winning huge praise for its response to the COVID-19 pandemic-riven as it is by divisions over everything from sharing resources to exit strategies-but the European Medicines Agency is coming out of it with flying colors, particularly for its timely responses to drug developers’ and clinicians’ needs.
The latest is a judicious reminder today of the risk of serious side effects with chloroquine and hydroxychloroquine, in the face of growing advocacy-including from such dubious medical authorities as US President Donald Trump-for its use in treating the novel coronavirus. EMA points out that these products are known to potentially cause heart rhythm problems that could be exacerbated at high dose or if combined with azithromycin or other medicines that have similar effects on the heart, as well as side effects on the liver and kidneys, nerve cell damage that can lead to seizures, and hypoglycemia. “Clinical data are still very limited and inconclusive, and the beneficial effects of these medicines in COVID-19 have not been demonstrated,” EMA says. “A number of large, randomized clinical trials are looking at the benefits and risks of chloroquine and hydroxychloroquine in patients with COVID-19,” it says, but “results from large, well-designed studies are needed to make any conclusions.”
But EMA’s engagement goes way beyond warnings. Already in March it created the COVID-19 pandemic task force, to manage and coordinate discussions on relevant product development, authorization and surveillance, and to conduct post-authorization follow-up of relevant authorized products. In particular, it is helping to meet the new challenges of the current health threat in the complexity of the disease, the variety of potential or repurposed medicinal products for prophylaxis or treatment, and the need for rapid clinical trials across Europe.
In April it has produced updated guidance for medicine developers and pharmaceutical companies to help speed up medicine and vaccine development and approval for COVID-19, advising on how they should address the regulatory challenges arising from the pandemic. This encourages developers of potential vaccines or treatments to contact EMA as soon as possible to discuss their strategy for evidence-generation. Scientific advice is free of charge and can be fast-tracked for potential novel coronavirus treatments or vaccines, it reminds developers. It is urging the EU research community to prioritize large randomized controlled clinical studies as the most likely to generate the conclusive evidence needed to enable rapid development and approval of potential treatments, and to include all EU countries in these trials. And it is encouraging the pooling of EU research resources into large-scale, multi-center, multi-arm clinical trials.
The agency has also produced advice for sponsors of other clinical trials affected by the pandemic, covering how they should adjust trial management during the pandemic – in situations where, for example, protocol deviations are needed for dealing with the need for isolating participants, or for limited access to public spaces or the reallocation of healthcare professionals. It outlines some regulatory flexibilities that can be applied to help pharmaceutical companies cope with the consequences of the pandemic, ranging from marketing authorizations and regulatory procedures to manufacturing and importation of active pharmaceutical ingredients and finished products, and from quality variations to labelling and packaging requirements. “EMA will be flexible and pragmatic during the assessment of affected clinical trial data submitted as part of marketing authorization applications”, it adds, encouragingly.
The agency is taking a leading part in a new series of meetings of the International Coalition of Medicines Regulatory Authorities, being convened bi-weekly to allow medicine regulators worldwide to exchange information and work together in speeding COVID-19 medicine and vaccine development and approval. It has launched, also in April, a fast-track monitoring system to help prevent and supply issues with crucial medicines used for treating COVID-19 patients.
And the agency’s staff-already strained by the shift from London to a temporary home in Amsterdam, and then a further shift into its new custom-built premises, as well as by staff sickness related to COVID-19-not only gave up their Easter break to keep essential work going to combat the pandemic, but they will also work through the upcoming Spring holiday between April 27 and May 1.
As Shakespeare, whose birthday is celebrated today, might have said of the agency,
“By how much unexpected, by so much
We must awake endeavor for defense;
For courage mounteth with occasion.”