Significant significance?

Modern medicine is a game of reason. The times harmonizing bodily fluids and quackery seem long gone. We no longer believe in phlebotomy or burning women to free our communities from bewitched spirits, even though bloodletting had occasionally worked based on chance for some medical practitioners during the Middle Ages. Individual experience still an invaluable skill any clinician, albeit more realm visual diagnosis than sensing imbalanced spirits. Ultimately, it was 18th century's period Enlightenment subsequent ~250 years scientific, rational, objective, most importantly evidence-based research that has paved way current state rapidly evolving continuously improving comprehension. So much theory. As with modern scientific theories, this not bad one. Hence, life expectancies have been growing since advent are now projected outgrow barriers by 2030 which commonly deemed unconquerable at beginning century.1, 2 These splendid results, facilitated plethora advances individual fields: HIV treatment only allows patient survival but may enable disease eradication plans.3 New kinds cancer treatments substantially changed lives millions patients around world.4, 5 countless phenomenal developments allowed make headway ridding world scourges humanity. What happens when desire advancement outruns healthy scepticism? It turns out, all glitters gold. infamous “Meta-Analysis Multiple Primary Prevention Trials Cardiovascular Events Using Aspirin” Bartolucci et al impressively highlighted pitfalls associated uncritical unchallenged quest evidence.6 indisputably well-written study examined acetylsalicylic acid (ASS) capability preventing myocardial infarction (MI) comprising data over 22.000 timespan average five years. authors reported P-value P < .00001, led recommendation ASS general population. indicated positive effect MI risk reduction beyond measure reasonable doubt. Another victory medicine, highly significant statistical analysis: Sounds great, doesn't it? Not so second sight: There simple very important insight missing while recommending basically everybody. While shown taking rate MIs, nobody cared what actually was. This where statistics get tricky: turned out be barely anything. Even smaller tenth percent there 0.77% correlation coefficient between intake reduced r2 = .001. actual single seemed clinically negligible furthermore did certainly up ASS’s adverse side effects. Subsequently, correct question ask is: How could happen? worth time take step back think about happened study. researchers P-value, indicating effect, case events under treatment. critical misinterpretation link low relevant effect. P-values indicate certainty hypothesis can claimed true tested against alpha-level. Less technical, tells us how likely observed truly rather chance, just like rolling six straight fair die. A would tell event thought backwards, sure we product chance. alpha-level decision boundary – below chosen alpha considered significant, greater generally interpreted as difference. Notably, value arbitrary set 0.05 due nothing else convention. Quite intuitively, after 10 rolled sixes heavily suspect die loaded tests suggest well alpha-levels. Measures play role science: Nobody want drug "proven" work if 40% "prove" being fallacious. Then again, something you know before drug: does help? Frustratingly, do anything size. Coming die, three ten suspicious 3.000 10.000 rolls leave convinced loaded. Markedly, both cases, same When playing games people care cheated little all, completely equal (such manufactured infinite precision). rightfully lot whether they badly. Translated into terms: Most P-values. They sizes. learned example layers interpretation calculation sizes discovered effects often add understanding Luckily, cases easily intuitively calculated. straight-up options 95% confidence intervals regression coefficients. Gail Sullivan Richard Feinn authored impactful editorial recommended short handbook reporting.7 Equally reporting interpret them correctly comprehensibly. At point asked look their readers perspective. intellectual paternalism enhancing papers readability interpretability readers. increasingly important, given fact overall output skyrocketed created specialized fields research.8 Of course, reading your own field might limit problem mostly things different one's everyday workflow spark creation original ideas. Unsurprisingly, limited clinical sciences, pronounced basic contexts. Fundamental myriad elaborate methods spans across vast domains. Scanning through recent physiological presents reader multitude tests, differently. forget, fundamental limitation biomedical sciences: Every experiment, every result, manmade therefore flawed model reality. allow estimate probability model's results choice appropriate feat pursuit. Staggeringly promise false-positive conclusions generalize adequately real-world scenarios while, vice versa, unsound selection lead large dependency found. No clear-cut exists determine best use too diverse, good rule thumb focus predictive scope. Biochemical models suited describe biological dependencies cellular level.9-11 Deeper down, capable characterizing specific intracellular pathways, broadening levels.12-14 examination complex systems depends focussing tissue organ-related, functional models, microscopical15, 16 macroscopical17, 18 levels. Research organ system interactions multifocal deep-down analysis must rely systemic mechanistic understanding.19-21 Then, questions require investigation whole body morphological behavioural traits living animals22 lastly, depend human subjects heaps related humans.23, 24 hard task choose many combination multiple insightful results. Interpreting those will described false negative interpretations. Physiologically comprehensible, well-described ideally dose-response relationship crucial first measures integrity offer complete synopsis crude sounds difficult, situation dire. Researchers should try address concern declining interprofessional readability, tools right easy administer. Explaining interpreting go emphasizing ideas helps guide reader's attention pivotal degree muscles fibres were expected grow protein levels rise key elements excellent papers, hunting down another decimal place. Our understanding, able trust works foundation medicine's wonders. community available accessible prevent Emphasizing plain contribution distance foregone maladministration. So, next writing paper present significance. conflict interest declare.