RCT and Evidence-informed Medicine

From Weekly I/O#77

Because randomized controlled trials have limitations in studying longevity, we should shift from evidence-based to evidence-informed medicine and adopt probabilistic strategies to live longer.

Book: Outlive

Randomized controlled trial(RCT) is a scientific method commonly used to determine cause and effect in simple, short-term studies. These trials form the basis of evidence-based medicine and advanced treatments like vaccines and cholesterol-lowering drugs, where studies involve relatively simple interventions and can be observed within a shorter period.

However, RCTs are of limited use in longevity research. Short-term studies can't reveal the full picture of diseases that take decades to unfold. Worse, beyond pharmacology, interventions involving exercise, nutrition, and sleep are very complex.

For example, an RCT can never map out a heart disease prevention plan using exercise for a healthy 40-year-old. It's simply unfeasible to monitor 10,000 people over their entire lifetimes with varying lifestyle interventions. Studying longevity itself in this way is almost impossible.

Therefore, a more practical option is to synthesize various existing data sources to form a strategy triangulating between them. Though these data sources aren't strong enough to be definitive when viewed separately, they can point us in a promising direction when taken together. The five data sources mentioned in the book are:

  1. Studies of centenarians, people who have lived to the age of one hundred and beyond
  2. Lifespan data from animals such as laboratory mice
  3. Human studies of the major diseases
  4. Molecular study of aging in both humans and animal
  5. Mendelian randomization

Without long-term RCTs to answer our questions with certainty, we must navigate health based on probabilities and risks. We shift from exclusively evidence-based to evidence-informed, risk-adjusted medicine.

Due to the uncertain nature, evidence-informed medicine is like charting an investment strategy. Based on what we know and our individual tolerance for risk at a given time, we adopt tactics to earn a better-than-average return of longevity. In other words, we utilize information to pursue a higher expected value of healthspan (aka longevity alpha).

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