The n-of-1 Clinical Trial: For Longevity Drugs?

The ultimate goal of an n-of-1 trial is to determine the optimal or best intervention for an individual patient using objective data-driven criteria. Such trials can leverage study design and statistical techniques associated with standard population-based clinical trials, including randomization, washout and crossover periods, as well as placebo controls. Despite their obvious appeal and wide use in educational settings, n-of-1 trials have been used sparingly in medical and general clinical settings. We briefly review the history, motivation and design of n-of-1 trials and emphasize the great utility of modern wireless medical monitoring devices in their execution. We ultimately argue that n-of-1 trials demand serious attention among the health research and clinical care communities given the contemporary focus on individualized medicine.

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Great post - I completely agree that this is likely the best way forward in the short term (and perhaps medium term also (decades) for longevity medicine. There will be an ongoing flow of research on drugs (old and new) that seem to provide healthy longevity benefits… but clinical trials are expensive and take a long time, so until those RCTs are completed, people will do their own “n-of-1 clinical trial”. If we can then gather that data from the early adopters, potentially working with academic groups who want to publish papers on them, we’ll all be making better decisions based on some good preliminary data.

I think we need to work with some researchers to help define in significant granularity what these “n-of-1” personal clinical trials should look like - so that we can all benefit from the more precise (compared to just anecdotal) knowledge that can be gained from these mini-clinical trials.

It seems like for any compound that is starting to show good evidence (e.g. success in the NIA ITP program for longevity outcomes in mice) that we should pull together a well designed “n-of-1 clinical trial” definition / outline that people can follow, then report back to everyone with positive or negative results. This would seem to help move the science forward as quickly as possible, and may also help spur the RCT clinical trials with larger populations that we all want also.

For example, I’d love to see some people with clinical trial design expertise (and n-of-1 clinical trial experience) design a program for people who want to test / try out:

  • Rapamycin
  • Canagliflozin/SLGT2 inhibitors
  • Acarbose
  • 17-alpha estradiol
  • Astaxanthin
  • Meclizine

Anyone here have any contacts in the industry / pharma / CROs , etc. want to take a stab at a generic n-of-1 clinical trial overview? Maybe we can crowdsource something like this - we have lots of doctors and pharmacists here, and medical researchers we can call on from time to time… I know we have visitors here from the Buck Institute, and other research universities focused on geroscience… this seems like a project we might be able to get some PostDocs interested in as a side project when they have some spare time…

Or maybe we could get some academics / PHD students to take this on as an individual project and we could try to get some funding for it from the Impetus grants or an individual donor.

I imagine we’d start with a generic outline for the Longevity n-of-1 clinical trial, then customize it for each drug, given the know background of the drug (for example some variables that we might want to test for - e.g. blood sirolimus levels - are unique to rapamycin, while other blood markers that we use in the Levine Phenotypic tests would be tracked in all the Compound-specific n-of-1 clinical trials.

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Between Dr Greens extensive patient pool, combined with this forum members, perhaps a good researcher could tease out a “statistical” signal so far? Distilling the n’s with those with tracking biomarkers, might render the pool pretty much underpowered and too many confounders to the point of meaningless to even start.

But a good suggestion balloon to float. We are grasping into the ether.

Obviously, part of the goal would be efficacy, but I’m also thinking more on the perspective of safety (i.e. phase 2 clinical trial) in healthy people. With enough people we start to see the true risk profile in healthy populations. I think most people here are more likely to adopt a potential longevity drug if the safety profile is good and known with some confidence. The better handle we have on the risk/reward tradeoff for any drug, the better we an all make decisions on whether to try it.

Everyone has a different risk/reward profile, and knowledge of pharma (and different health profiles and age) so people will try drugs at different points as we learn about new longevity drugs.

By making the individual “trials” of these longevity drugs more scientific, we can all learn from each other faster, with a better knowledge base. Even if its something like the Rapamycin Survey Study that Matt Kaeberlein/Jonathan An are doing at University of Washington… but based on more structured data gathered in an organized fashion with specific goals in mind.

Basically, I’m trying to make it so we are effectively crowd-sourcing the type of clinical trial that Joan Mannick did in the 2014 Everolimus study that really kicked off rapamycin use. We knew the upside from the mouse studies, but we needed the downside risk in healthy populations before people would start adopting the drug. Now we need the same sort of data on all the other longevity drug candidates as they come down the pipe, and we need to know about how the combinations work and impact our biology.

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One attempt at an n-of-1 clinical trial definition, for senolytic drug Dasatinib.

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