Enhancing Alzheimer’s research with insights from COVID-19 trials

These COVID times have proved an immense challenge to clinical trials. At times of course clinical activity has had to pause entirely in some sites in some countries or regions. But overall trials teams have worked hard to keep trials running with more success than failure. This has required huge efforts from all parts of the team and I take my hat off to those research teams that have strived hard to keep research teams and clinical colleagues engaged and have managed to assess patients safely. We all look forward to when trials activity can resume at full strength.

Of course there is another medical challenge of near equal size (now is not the time, but sadly this is true however so measured; by patient numbers, by mortality, even by economic cost and impact on families). That medical challenge is Alzheimer’s disease and related disorders causing dementia. How then can we learn from the COVID19 experience and can we get faster to therapies? We could break this down into the challenge for preclinical science (‘the labs’), the challenge for clinical science and clinical trials and challenge for public policy. But what of clinical trials? What are the lessons from COVID19 for dementia research? There are many but three in particular stand out for me. First, speeding development, second, the importance of tests and third, the importance of trials in the community.

The normal process of clinical development is to test one therapeutic compound at a time in sequential phases. But COVID trials haven’t been constrained by this. The Oxford RECOVERY trial tests many compounds at the same time on a rolling platform for example, some of the clinical trials merge concept and efficacy phases and all of the trials have proceeded at warp speed in close conjunction with regulatory authorities. We could use some of that speed in dementia research. The IMI-EPAD programme was an important exploratory approach to such trial acceleration and I predict that we will see a growth of similar initiatives as the number of promising therapeutics grows. Second, the importance of tests. We have all become pretty familiar with the language of PCR and lateral flow tests, of antigen and antibody testing and, at least on my twitter feed, on the virtues of positive and negative predictive values as accuracy measures. Astonishing! A year ago, lots of scientists working in this very field struggled with some of this and now it’s on the news most days. But the important point is that tests matter. Tests, or biomarkers, for disease activity are what have enabled all of the research for COVID vaccines and without them we would still be at square one. Luckily, biomarkers for Alzheimer’s have also hit the big-time and we now have very specific imaging (PET) markers as well as spinal fluid CSF markers and even blood markers that are just as good in final stages of development. I guarantee that this will change the way we do clinical trials; making them faster to recruit, faster to read-out and most importantly, more effective in giving an answer to whether any particular drug works.

We do need to implement these biomarkers as widely and rapidly as we can and that’s why initiatives such as the Oxford Brain Health Clinic set up by Clare Mackay and colleagues are so very important. We will also need other biomarkers, to predict likely Alzheimer’s pathology as well as to stratify or group people into sub-categories in order to measure change even before symptoms have started. The work that Ivan Koychev and Alejo Nevado-Holgado are important here and the Deep and Frequent Phenotyping study headed by Vanessa Raymont with Jen Lawson is to my mind the study most likely anywhere in the world, to give us a test we can use to speed up clinical trials in that all-important phase 2, proof of concept stage.

Finally, everything about the COVID experience has taught us we can do a lot from home (even if some of us are a little fed-up of it). That is true also for clinical trials and, more specifically, those in dementia research. When we want to measure memory then why do it with a pencil and paper test every three months in the clinic? Could we not use a remote assessment on the smartphone, tablet or some other device, just as well and if we did this more often than every three months might we not get better data? If we want to assess long term outcomes could we not do this from the patient’s electronic medical record? Might we perhaps do some of the data-collection by video or phone and thereby stay in even closer contact to our trials participants by having more frequent interactions than we can do if we only have them in the clinic? Of course the clinical trials unit space will always be necessary and not least because many of the therapies in development for Alzheimer’s are infusions or other complex interventions. But if we could implement at least some of the trials-at-home technologies we might be able to do much larger trials, more quickly. And we might find that participants welcome such innovations.

So although this past year has been devastating beyond belief for so many people and as all of us have suffered to a greater or lesser degree, and despite the fact that we are far from out of it as I write, I do see much to be thankful for. More than anything else I see some of the best science humankind has ever produced and at a speed that is breathtaking. I think we can learn from that and if we can bring even a small amount of that learning to dementia research then I think we can speed our path to an effective therapy for what will remain one of the world’s most devastating disorders long after we have got COVID under control.