Clinical trials in the pandemic age: What is fit for purpose?

It is critical to ensure that COVID-19 studies provide clear and timely answers to the scientific questions that will guide us to scalable solutions for all global regions. Significant challenges in operationalizing trials include public policies for managing the pandemic, public health and clinical capacity, travel and migration, and availability of tests and infrastructure. These factors lead to spikes and troughs in patient count by location, disrupting the ability to predict when or if a trial will reach recruitment goals. The focus must also be on understanding how to provide equitable access to these interventions ensuring that interventions reach those who need them the most, be it patients in low resource settings or vulnerable groups.  We introduce a website to be used by The Bill & Melinda Gates Foundation, Wellcome Trust, and other funders of the COVID Therapeutics Accelerator that accept proposals for future clinical research. The portal enables evaluations of clinical study applications that focus on study qualities most likely to lead to informative outcomes and completed studies.

Younger ages at risk of Covid-19 mortality in communities of color.

More than 85% of Covid-19 mortality in high income countries is among people 65 years of age or older. Recent disaggregated data from the UK and US show that minority communities have increased mortality among younger age groups and in South Africa initial data suggest that the majority of deaths from Covid-19 are under 65 years of age. These observations suggest significant potential for increased Covid-19 mortality among younger populations in Africa and South Asia and may impact age-based selection of high-risk groups eligible for a future vaccine.

Precisely Tracking Childhood Death.

Little is known about the specific causes of neonatal and under-five childhood death in high-mortality geographic regions due to a lack of primary data and dependence on inaccurate tools, such as verbal autopsy. To meet the ambitious new Sustainable Development Goal 3.2 to eliminate preventable child mortality in every country, better approaches are needed to precisely determine specific causes of death so that prevention and treatment interventions can be strengthened and focused. Minimally invasive tissue sampling (MITS) is a technique that uses needle-based postmortem sampling, followed by advanced histopathology and microbiology to definitely determine cause of death. The Bill & Melinda Gates Foundation is supporting a new surveillance system called the Child Health and Mortality Prevention Surveillance network, which will determine cause of death using MITS in combination with other information, and yield cause-specific population-based mortality rates, eventually in up to 12-15 sites in sub-Saharan Africa and south Asia. However, the Gates Foundation funding alone is not enough. We call on governments, other funders, and international stakeholders to expand the use of pathology-based cause of death determination to provide the information needed to end preventable childhood mortality.

Honing the Priorities and Making the Investment Case for Global Health.

In the aftermath of the Ebola crisis, the global health community has a unique opportunity to reflect on the lessons learned and apply them to prepare the world for the next crisis. Part of that preparation will entail knowing, with greater precision, what the scale and scope of our specific global health challenges are and what resources are needed to address them. However, how can we know the magnitude of the challenge, and what resources are needed without knowing the current status of the world through accurate primary data? Once we know the current status, how can we decide on an intervention today with a predicted impact decades out if we cannot project into that future? Making a case for more investments will require not just better data generation and sharing but a whole new level of sophistication in our analytical capability--a fundamental shift in our thinking to set expectations to match the reality. In this current status of a distributed world, being transparent with our assumptions and specific with the case for investing in global health is a powerful approach to finding solutions to the problems that have plagued us for centuries.

Transient inability to distinguish between faces: electrophysiologic studies.

It is not known with certainty at which level of face processing by the cortex the distinction between a familiar and an unfamiliar face is made. Subdural electrodes were implanted under the fusiform gyrus of the right temporal lobe in a patient who developed an unusual inability to distinguish differences between faces as part of the epileptic aura ("all faces looked the same"). A cortical region located posterior to the epileptic focus was identified that exhibited a maximum evoked response to the presentation of facial images (N165), but not to objects, scenes, or character strings. Evoked potentials elicited by a variety of visual images indicated that any perturbation away from novel whole-face stimuli produced submaximal responses from this region of the right temporal lobe. Electrical stimulation of this region resulted in an impairment of face discrimination. It was found that presentation of familiar faces (grandmother, treating physician) produced a different response from that observed for novel faces. These observations demonstrate that within 165 msec of face presentation, and before the conscious precept of face familiarity has formed, this cortical region has already begun to distinguish between a familiar and an unfamiliar face.