Can any meaningful conclusions of efficacy/harm ever be drawn form individual experience/"self experimentation"?
Hi. This post might irritate, but I mean well. It's prompted by a useful article I read this morning...about the nocebo effect with statin's. https://www.nejm.org/doi/full/10.1056/NEJMc2031173
I reflected on other examples of therapy that "everyone" knew were effective... say arthroscopic debridement in patients with degenerative knee disease. In fact hundreds of millions of dollars spent yearly... until this...https://pubmed.ncbi.nlm.nih.gov/12110735/
Note the use of sham surgery...a requirement for surgical RCT's.
In my case I elected to have a thymectomy for my MG, based on a solid, randomized, but not sham-surgery-controlled trial... believe me, a thymectomy is one hell of a placebo...but I remain hopeful that the observed effects (a massive decrease in steroid dose and a huge decrease in time spent on a ventilator in the ICU...were not just because of the impact of belief on immune response.
I am one who takes Rapamycin (in my case to treat autoimmune disease, not to "live longer"). I made the decision to start because of both experimental MG data (in mice) and the magnitude of other mechanistic data as well as limited case-series and small trials in other autoimmune disease. I hope it's a good call... but I do not know its a good call!
I'm doing well... but have no idea whatsoever whether my current status is as a result of the Rapamycin...or in spite of it. This is because I as an individual, I have only taken one path... the one that includes Rapamycin.
I know many on this site believe they can tell whether a given medicine has helped (this includes physicians who prescribe medications to others), and whether their side-effects are due to the medication, whether perceived benefits result from the intervention.
I believe this is a false assumption. The history of medicine should demonstrate to anyone who pays attention, that both open label trials as well as case-control studies cannot effectively determine efficacy. If you disagree, please present your evidence.
I once conducted an n of 1 trial in family practice. A kid was labelled as having ADHD and put on Ritalin by a pediatric neurologist. Nearly everyone was happy... the doc, the school (in particular), and one of the parents. The dad, recalling his happy but active youth... was not. I was open...
With some effort, we elected to do a trial. I got a local pharmacist to make up active and placebo medications. The parents and all teachers agreed to complete daily ADHD scores using a validated tool (so long ago I cannot remember specifics). We cycled (in random order determined by the pharmacist) between active drug and placebo. After repeated cycles (either 7 or 9), the trial was stopped (partly because the school was agitating because of perceptions of problematic behaviour during what they were sure was the placebo weeks). The results were analyzed..and eventually the code was broken.
There was zero impact of the Ritalin and the boys behaviour. Now Ritalin is a perfect drug for this sort of trial, because its effects occur rapidly and diminish equally rapidly. This is not the case with Rapamycin). Of note, even when evidence of lack of efficacy was presented to the school, they refused to accept it...because they knew the Ritalin worked. They went so far to say that the child would not be allowed back... unless he was drugged. So much for the scientific medicine.
So, my rhetorical question is: are the interventions you are engaged in, helping you, hurting you, or neutral? How do you know? Is it based on belief...or knowledge? Could you be making the same attribution errors that have occurred thousands of times in the history of medicine?
As I said earlier, I hope the Rapamycin is helping me... but I do not know this...
Looking forward to a useful discussion...
BTW... another sham controlled RCT but this time for meniscus tear... https://www.nejm.org/doi/full/10.1056/NEJMoa1305189
I can provide hundreds of examples...where the observed benefits held by both doc's and patients..were due to the placebo effect.
Mark, I agree this is the crux of the challenge...quantifying (hard scientific data) anti-aging benefit of our interventions? Forget all the mice studies and theories...what's the actual biological impact on HUMANS? We know from a plethora of studies that superior cardio respiratory fitness is a proven life extender in humans. As pharmacological interventions have become more mainstream, how do we prove efficacy whilst the large scale human RCT studies are missing (and very likely may never get done)?
Can you share your rapamycin regiment and did you do a Horvath epigenetic before and after intervention re your "fairly significant impact on biological age comment"? And did you undertake other epigenetic interventions in the interim that may have also contributed to the reduction, and possibly confounding the sole rapamycin effect?
I have implemented a range of interventions over the last 4 years, and a first (recent) Horvath test came back 52 yrs vs 55 actual. I plan to another in another in say 5 yrs. I am also tracking blood biomarkers, CCAC, volumetric brain MRI, neuropsychological testing to try and "scientifically" track my progression. I am trying to put aside any placebo effect, and rely solely on the data.
I am not certain of anything...sigh. But as an engineer, I have to instinctively go on the data. Am I stronger, fitter, low inflammation, no chronic disease or ailments, stellar biomarkers, clean arteries, large and unshrinking hippocampus, good memory, etc. But...I do not discount the overall "health and well being" effect being actually holistically and biologically mechanistic by some unmeasurable pathways. I can tell you 100% I feel a lot better about myself re health and my aging outlook than I did 4 years ago simply due to actually having mental fortitude to start and MAINTAIN the lifestyle changes. This mental sentiment may be very powerful indeed.
We may NEVER know what is singularly or in combination causal. But one can either be purist process or transactionally end result driven. On the latter, why not embark on implementing everything one thinks is beneficial, knowing full well the interventions not singularly trackable for cause, yet monitor and MEASURE an actual positive biological outcome? I really couldn't care less which of the myriad of interventions, individually or synergistically, makes me live healthier and longer...as long as I do. Yes, I am science and process driven to select the levers, but ultimately, all I care about is outcome.
Mac. Would that extend to a positive outcome if all due to a placebo effect? It is also possible that some interventions are helpful...and others detrimental but there is a net benefit... it really is a problem for which I do not have a solution. I won't either, until RCT's are conducted for each intervention...and they will be done.
Yes, I always discount stories about someone feeling better, claiming better mental acuity or improved mood.
my personal testing regime
life extension comprehension male panel every 6 months
epigenetic testing annually
a daily measure of:
sleep (total, deep, REM)
About 90% of these markers have improved in the last 12 months, the others neutral ( hard to improve BP of 104/64 or RHR of 48)
so I don’t think this is all placebo