Trial reportBMC medical research methodology2023
The heterogeneity of symptom reporting across study sites: a secondary analysis of a randomised placebo-controlled multicentre antimalarial trial.
Trial report in BMC medical research methodology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01814683 (Improving the Radical Cure of Vivax Malaria), which is not on this map. Cited by 3 papers, 3 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Improving the Radical Cure of Vivax Malaria: A Multicentre Randomised Comparison of Short and Long Course Primaquine Regimens
Who cites it
3 citing papers in PubMed, 3 syntheses or guidelines pooled it.
- Analysis of the effect of primaquine dose on efficacy, safety, and tolerability in patients with Plasmodium vivax malaria in Ethiopia: a systematic review and individual patient data meta-analysis.Malaria journal · 2026Pooled it
- Automated reporting of primaquine dose efficacy, tolerability and safety for Plasmodium vivax malaria using a systematic review and individual patient data meta-analysis.Malaria journal · 2025Pooled it
- Primaquine for uncomplicated Plasmodium vivax malaria in children younger than 15 years: a systematic review and individual patient data meta-analysis.The Lancet. Child & adolescent health · 2024Pooled it
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
27 authors.
Funding
Abstract
introductionSymptoms reported following the administration of investigational drugs play an important role in decisions for registration and treatment guidelines. However, symptoms are subjective, and interview methods to quantify them are difficult to standardise. We explored differences in symptom reporting across study sites of a multicentre antimalarial trial, with the aim of informing trial design and the interpretation of safety and tolerability data.
methodsData were derived from the IMPROV trial, a randomised, placebo-controlled double blinded trial of high dose primaquine to prevent Plasmodium vivax recurrence conducted in eight study sites in Afghanistan, Ethiopia, Indonesia and Vietnam. At each follow up visit a 13-point symptom questionnaire was completed. The number and percentage of patients with clinically relevant symptoms following the administration of primaquine or placebo, were reported by study site including vomiting, diarrhoea, anorexia, nausea, abdominal pain and dizziness. Multivariable logistic regression was used to estimate the confounder-adjusted site-specific proportion of each symptom.
resultsA total of 2,336 patients were included. The greatest variation between sites in the proportion of patients reporting symptoms was for anorexia between day 0 and day 13: 97.3% (361/371) of patients in Arba Minch, Ethiopia, reported the symptom compared with 4.7% (5/106) of patients in Krong Pa, Vietnam. Differences attenuated slightly after adjusting for treatment arm, age, sex, day 0 parasite density and fever; with the adjusted proportion for anorexia ranging from 4.8% to 97.0%. Differences between sites were greater for symptoms graded as mild or moderate compared to those rated as severe. Differences in symptom reporting were greater between study sites than between treatment arms within the same study site.
conclusionDespite standardised training, there was large variation in symptom reporting across trial sites. The reporting of severe symptoms was less skewed compared to mild and moderate symptoms, which are likely to be more subjective. Trialists should clearly distinguish between safety and tolerability outcomes. Differences between trial arms were much less variable across sites, suggesting that the relative difference in reported symptoms between intervention and control group is more relevant than absolute numbers and should be reported when possible.
trial registrationClinicaltrials.gov: NCT01814683; March 20
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