Trustworthiness and Transparency Features Were Less Frequent in Randomized Trials Presenting Large Effects in Abstracts

OBJECTIVESLarge effect sizes (ESs), especially when prominently presented in trial abstracts, draw large attention, but it is important to understand whether they are trustworthy. We aimed to assess indicators of transparency and trustworthiness in randomized controlled trials (RCTs) reporting some large ES in their abstract, in comparison with RCTs presenting only non-large ESs in their abstract. STUDY DESIGN AND SETTINGWe included RCTs indexed in MEDLINE between January 1, 2024 and March 18, 2025, presenting at least one standardized mean differences of absolute value 0.8 or higher (large ES) versus those presenting only smaller absolute standardized mean differences in their abstract. Trial characteristics and methodological features were extracted systematically in large ES and non-large ES trials. Primary outcome was pre-specified protocol registration, secondary outcomes were having no protocol and public availability or repository placement of raw data. RESULTSWe evaluated 152 trials with large ESs in their abstract and 175 trials with only non-large ESs in their abstract. Large ES trials had suggestively lower rates of pre-registered protocols (45% versus 61%, p=0.0054) and significantly higher rates of no protocol registration (26% versus 13%, p=0.0028) than non-large ES trials. There was no difference in raw data public availability or repository placement (6% versus 7%). Large ES trials were also less likely to be multicenter (p=0.0042), to have high-income country of corresponding author (p=0.0001), to be conducted in high-income country site(s) (p=0.0003), to have a published statistical analysis plan (p=0.0216), and to result from between-group comparisons (p<0.0001). Large effects were significantly more likely to involve non-drug/non-psychological interventions (p=0.0001). CONCLUSIONSRCTs presenting large ESs in their abstracts are more likely to lack transparency and trustworthiness features and may operate with higher risk of lack of credibility. HighlightsO_LIThis meta-research study assessed the association of effect sizes with features of transparency and trustworthiness of RCTs C_LIO_LILarge effect trials have fewer registered and available protocols C_LIO_LIStudies with large effects sizes are more likely to have a smaller sample size, single center recruitment and provenance from countries without strong clinical research tradition C_LIO_LIData sharing is poor across all trials regardless of effect size C_LI What is new?O_ST_ABSKey findingsC_ST_ABSO_LIThis meta-research study indicated that RCTs presenting large effect sizes in their abstracts are more likely to lack features of transparency and trustworthiness. C_LI What this adds to what is known?O_LILarge effect sizes in abstracts of trials draw attention and may seem as compelling evidence for a studys claim. Yet there have been divergent findings concerning the association between effect size and credibility of a trial. Our study showed that large effect sizes are consistently associated with a range of methodological shortcomings. C_LI What is the implication and what should change now?O_LIRCTs presenting large effect sizes may operate with higher risk of lack of credibility. C_LIO_LIRather than indicating a convincing finding, extreme results should be met with increased attention and careful scrutiny. C_LI