Hypothesis

Sildenafil given during pregnancies complicated by severe early-onset fetal growth restriction would change fetal-placental gene programming related to cardiovascular and renal development.

What failed

Whole-genome RNA sequencing of umbilical vein endothelial cells (12 sildenafil, 8 placebo) and placentas (13 per group) from the Dutch STRIDER trial showed similar expression profiles between groups; sildenafil did not change cardiovascular or renal programming.

Broken assumption

Prenatal sildenafil reprogrammes the cardiovascular and renal development of growth-restricted fetuses.

Why

A few placental gene sets involved in the nitric oxide pathway were altered, which the authors read as reflecting sildenafil's mechanism of action, along with upregulated immune-pathway gene sets — but no reprogramming of cardiorenal health.

From the published paper: Terstappen et al. Journal of Trial and Error, 2023. ↗CC BY

Hypothesis

Two 200 ml transfusions of convalescent plasma would reduce the need for non-invasive or mechanical ventilation in patients with severe COVID-19.

What failed

In an open-label pilot of 20 plasma versus 20 standard-care patients, ventilation was needed by 4 and 6 respectively (risk ratio 0.67, 95% CI 0.22-2.0, p = 0.72); time on ventilation, biochemical measures and 28-day mortality did not differ.

Broken assumption

Passive antibody transfer from recovered patients improves respiratory outcomes once COVID-19 is already severe.

Why

The authors note the pilot was small and that the plasma group was higher risk at baseline; they call for a larger definitive trial.

From the published paper: AlQahtani et al. Scientific Reports, 2021. ↗CC BY

Hypothesis

Mild age-related vestibular loss (presbyvestibulopathy) explains a meaningful share of dizziness in patients aged 60 and over.

What failed

Among 102 consecutive patients aged 60+ in a subspecialty dizziness clinic, 68.6% had normal vestibular function and only 6.9% had mild bilateral hypofunction. Presbyvestibulopathy was the final diagnosis in just 2.9% (3 patients), and all three had treatable comorbidities such as anxiety.

Broken assumption

Age-related vestibular decline is common enough, and explanatory enough, to account for dizziness in the elderly.

Why

Vestibulo-ocular reflex gain did decline with age (0.96 at 60–69 to 0.77 at 80+, p < 0.001), but most older patients still had normal gains, so the authors conclude a more specific vestibular diagnosis is usually more appropriate.

From the published paper: Chang et al. Frontiers in Neurology, 2026. ↗CC BY

Hypothesis

A short subset of odours that Parkinson's patients selectively fail to identify would discriminate patients from controls better than the full 40-item UPSIT or a random set of items.

What failed

Several 12-item subsets beat 12 random items in a discovery cohort of 314 patients and 314 controls, but in two independent validation cohorts (306 patients, 343 controls) they matched the full test without outperforming 12 random items.

Broken assumption

Parkinson's disease impairs identification of specific odours more than others, in a way that is stable across patient groups.

Why

The ranking of which odours discriminate best did not hold across cohorts, which the authors read as evidence against odour-selective smell loss in Parkinson's disease.

From the published paper: Morley et al. npj Parkinson s Disease, 2018. ↗CC BY

Hypothesis

The observed correlation between effective spin and mass ratio is a property of the binary black hole population itself.

What failed

Fitting the two recently identified subpopulations separately, the correlation weakened significantly or disappeared altogether for the low-mass subpopulation once a second effective-spin distribution was allowed for the high-mass one, and Bayesian evidence strongly favoured two separate spin distributions over one mass-ratio-dependent distribution (ln B > 4.2).

Broken assumption

A correlation measured across the whole catalogue reflects a relationship within a single population.

Why

The authors conclude the correlation in the overall population is explained by the superposition of two distinct subpopulations, the high-mass one plausibly from hierarchical mergers.

From the published paper: Li et al. The Astrophysical Journal, 2025. ↗CC BY

Hypothesis

Cobalt phthalocyanine on carbon nanotubes should reduce CO2 to methanol regardless of whether the catalyst is monomeric or aggregated, which would explain why decades of earlier work missed the reaction.

What failed

Density-functional calculations of monomeric and dimeric CoPc found that for the dimer, CO dissociation is always favoured over the extra reduction needed to form the Co–CHO⁻ intermediate, so the methanol path is effectively blocked; only the monomer makes it competitive at more negative potentials.

Broken assumption

The catalyst's aggregation state does not change which CO2-reduction product it makes.

Why

The authors attribute the dimer's harder reduction to repulsive interactions between the CoPc units and weaker solvent stabilisation of charge in the aggregate.

From the published paper: Chen et al. Organometallics, 2021. ↗CC BY

Hypothesis

Adding fenofibrate to statin therapy would lower cardiovascular events in high-risk patients with type 2 diabetes, compared with a statin alone.

What failed

Across 5,518 patients followed for a mean 4.7 years, the primary outcome (nonfatal MI, nonfatal stroke or cardiovascular death) ran at 2.2% a year with fenofibrate vs 2.4% with placebo (HR 0.92, P=0.32), with no difference on any secondary outcome.

Broken assumption

Lowering triglycerides with a fibrate adds cardiovascular protection on top of a statin in type 2 diabetes.

Why

The combination did not reduce events in the trial population as a whole. Prespecified subgroups hinted at benefit in men and in patients with both high triglycerides and low HDL, and possible harm in women — the authors treat these as hypotheses, not findings.

From the published paper: ACCORD Study Group. N Engl J Med, 2010. NCT00000620 ↗

Hypothesis

Individual exploratory behaviour would be consistent across contexts and over time in corvids, as expected if exploration is a personality trait.

What failed

In pinyon jays, Clark's nutcrackers, California scrub jays and black-billed magpies tested on novel-environment and novel-object tasks over repeated trials, individuals' exploration was repeatable neither across tasks nor across time.

Broken assumption

Exploration is a stable individual trait in all birds that show it.

Why

The authors find no evidence that exploration is a personality trait in these species; differences appeared only at the species level, possibly linked to how much each relies on cached food.

From the published paper: Vernouillet et al. Scientific Reports, 2020. ↗CC BY

Hypothesis

The most physically complete equation, Penman-Monteith, gives the best global daily reference potential evaporation for hydrological models.

What failed

Evaluated against Penman-Monteith values derived from CRU data, Penman-Monteith applied to CFSR did not outperform the simpler equations; it returned relatively low values in arid regions such as the Sahara, central Australia and the US deserts, which pushed discharge too high for dry basins including the Orange, Murray and Zambezi. The cell-specific recalibrated Blaney-Criddle fitted best but proved unstable under changing climate and less reliable for daily series, and in many basins the choice of method barely changed simulated river flow at all.

Broken assumption

The most physically complete evaporation equation is the most accurate when driven by reanalysis data.

Why

The authors blame the equation’s heavy data demand and its sensitivity to inaccuracy in the input data, and recommend a recalibrated Hargreaves form instead.

From the published paper: Weiland et al. Hydrology and earth system sciences, 2012. ↗CC BY