Evaluating Science: Clinical Trials, Epidemiology, Preclinical Studies & Mendelian Randomization | George Davey Smith | 265

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Methods & challenges of establishing causal relationships in health research, emphasizing epidemiology, randomized trials, and genetic approaches.

Topics:

• Epidemiology: Studies disease influences using observational designs like case-control and prospective cohorts, plus trials, to identify patterns and test hypotheses.
• Hierarchy of evidence critique: Rejects rigid pyramids favoring RCTs, as all studies can be biased; advocates triangulation integrating varied data types for robust conclusions.
• RCT strengths & weaknesses: Randomization balances confounders, but issues like poor blinding, attrition, or subversion can undermine results; large samples may yield spurious precision if biased.
• Confounding & reverse causation: Examples include yellow fingers and lung cancer (both from smoking) or early atherosclerosis inflating CRP-disease links; hard to fully control statistically.
• Nutrition epidemiology: Observational studies often overstate benefits (e.g., vitamin E for heart disease), leading to failed trials; incentives favor new findings over revisiting errors.
• Mendelian randomization: Uses genetic variants as proxies for exposures (e.g., ALDH2 for alcohol metabolism) to mimic randomization; reveals no heart benefits from alcohol, unlike observational data.
• Negative controls: Tests implausible outcomes (e.g., smoking and murder) or exposures (e.g., paternal smoking in pregnancy) to check for confounding artifacts.
• Evidence triangulation: Combines diverse studies with different biases (e.g., cross-cultural comparisons) for causality; applied to dismiss HDL-raising drugs despite initial promise.

Practical Takeaways:

• Scrutinize health claims by checking for negative controls or variety in evidence sources to avoid mistaking correlation for causation.
• For personal decisions like alcohol intake, consider genetic studies showing risks at all levels, and aim for moderation or abstinence based on overall evidence.
• When evaluating supplements or diets, prioritize trials over observational data, and question media hype that ignores confounding factors.

About the guest: Dr. George Davey Smith, MD, DSc is a professor of clinical epidemiology at the University of Bristol and director of the MRC Integrative Epidemiology Unit.

*Not medical advice.

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