The heterogeneity of symptom reporting across study sites: a secondary analysis of a randomised placebo-controlled multicentre antimalarial trial
<p><strong>Introduction</strong> Symptoms 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 standard...
| Asıl Yazarlar: | , , , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Materyal Türü: | Journal article |
| Dil: | English |
| Baskı/Yayın Bilgisi: |
BioMed Central
2023
|
| _version_ | 1826311201184808960 |
|---|---|
| author | Thriemer, K Commons, RJ Rajasekhar, M Degaga, TS Chand, K Chau, NH Assefa, A Naddim, MN Pasaribu, AP Rahim, AG Sutanto, I Hien, TT Hailu, A Hasanzai, MA Ekawati, LL Woyessa, A Teferi, T Waithira, N Taylor, WRJ Ley, B Dondorp, A Baird, JK White, NJ Day, NP Price, RN Simpson, JA von Seidlein, L |
| author_facet | Thriemer, K Commons, RJ Rajasekhar, M Degaga, TS Chand, K Chau, NH Assefa, A Naddim, MN Pasaribu, AP Rahim, AG Sutanto, I Hien, TT Hailu, A Hasanzai, MA Ekawati, LL Woyessa, A Teferi, T Waithira, N Taylor, WRJ Ley, B Dondorp, A Baird, JK White, NJ Day, NP Price, RN Simpson, JA von Seidlein, L |
| author_sort | Thriemer, K |
| collection | OXFORD |
| description | <p><strong>Introduction</strong> Symptoms 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.</p>
<p><strong>Methods</strong> Data 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.</p>
<p><strong>Results</strong> A 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.</p>
<p><strong>Conclusion</strong> Despite 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.</p>
<p><strong>Trial registration</strong> Clinicaltrials.gov: NCT01814683; March 20th, 2013.</p> |
| first_indexed | 2024-03-07T08:04:50Z |
| format | Journal article |
| id | oxford-uuid:3bebe451-05e6-453e-b6bc-aec694f0e3b9 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T08:04:50Z |
| publishDate | 2023 |
| publisher | BioMed Central |
| record_format | dspace |
| spelling | oxford-uuid:3bebe451-05e6-453e-b6bc-aec694f0e3b92023-10-30T14:58:43ZThe heterogeneity of symptom reporting across study sites: a secondary analysis of a randomised placebo-controlled multicentre antimalarial trialJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:3bebe451-05e6-453e-b6bc-aec694f0e3b9EnglishSymplectic ElementsBioMed Central2023Thriemer, KCommons, RJRajasekhar, MDegaga, TSChand, KChau, NHAssefa, ANaddim, MNPasaribu, APRahim, AGSutanto, IHien, TTHailu, AHasanzai, MAEkawati, LLWoyessa, ATeferi, TWaithira, NTaylor, WRJLey, BDondorp, ABaird, JKWhite, NJDay, NPPrice, RNSimpson, JAvon Seidlein, L<p><strong>Introduction</strong> Symptoms 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.</p> <p><strong>Methods</strong> Data 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.</p> <p><strong>Results</strong> A 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.</p> <p><strong>Conclusion</strong> Despite 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.</p> <p><strong>Trial registration</strong> Clinicaltrials.gov: NCT01814683; March 20th, 2013.</p> |
| spellingShingle | Thriemer, K Commons, RJ Rajasekhar, M Degaga, TS Chand, K Chau, NH Assefa, A Naddim, MN Pasaribu, AP Rahim, AG Sutanto, I Hien, TT Hailu, A Hasanzai, MA Ekawati, LL Woyessa, A Teferi, T Waithira, N Taylor, WRJ Ley, B Dondorp, A Baird, JK White, NJ Day, NP Price, RN Simpson, JA von Seidlein, L The heterogeneity of symptom reporting across study sites: a secondary analysis of a randomised placebo-controlled multicentre antimalarial trial |
| title | The heterogeneity of symptom reporting across study sites: a secondary analysis of a randomised placebo-controlled multicentre antimalarial trial |
| title_full | The heterogeneity of symptom reporting across study sites: a secondary analysis of a randomised placebo-controlled multicentre antimalarial trial |
| title_fullStr | The heterogeneity of symptom reporting across study sites: a secondary analysis of a randomised placebo-controlled multicentre antimalarial trial |
| title_full_unstemmed | The heterogeneity of symptom reporting across study sites: a secondary analysis of a randomised placebo-controlled multicentre antimalarial trial |
| title_short | The heterogeneity of symptom reporting across study sites: a secondary analysis of a randomised placebo-controlled multicentre antimalarial trial |
| title_sort | heterogeneity of symptom reporting across study sites a secondary analysis of a randomised placebo controlled multicentre antimalarial trial |
| work_keys_str_mv | AT thriemerk theheterogeneityofsymptomreportingacrossstudysitesasecondaryanalysisofarandomisedplacebocontrolledmulticentreantimalarialtrial AT commonsrj theheterogeneityofsymptomreportingacrossstudysitesasecondaryanalysisofarandomisedplacebocontrolledmulticentreantimalarialtrial AT rajasekharm theheterogeneityofsymptomreportingacrossstudysitesasecondaryanalysisofarandomisedplacebocontrolledmulticentreantimalarialtrial AT degagats theheterogeneityofsymptomreportingacrossstudysitesasecondaryanalysisofarandomisedplacebocontrolledmulticentreantimalarialtrial AT chandk theheterogeneityofsymptomreportingacrossstudysitesasecondaryanalysisofarandomisedplacebocontrolledmulticentreantimalarialtrial AT chaunh theheterogeneityofsymptomreportingacrossstudysitesasecondaryanalysisofarandomisedplacebocontrolledmulticentreantimalarialtrial AT assefaa theheterogeneityofsymptomreportingacrossstudysitesasecondaryanalysisofarandomisedplacebocontrolledmulticentreantimalarialtrial AT naddimmn theheterogeneityofsymptomreportingacrossstudysitesasecondaryanalysisofarandomisedplacebocontrolledmulticentreantimalarialtrial AT pasaribuap theheterogeneityofsymptomreportingacrossstudysitesasecondaryanalysisofarandomisedplacebocontrolledmulticentreantimalarialtrial AT rahimag theheterogeneityofsymptomreportingacrossstudysitesasecondaryanalysisofarandomisedplacebocontrolledmulticentreantimalarialtrial AT sutantoi theheterogeneityofsymptomreportingacrossstudysitesasecondaryanalysisofarandomisedplacebocontrolledmulticentreantimalarialtrial AT hientt theheterogeneityofsymptomreportingacrossstudysitesasecondaryanalysisofarandomisedplacebocontrolledmulticentreantimalarialtrial AT hailua theheterogeneityofsymptomreportingacrossstudysitesasecondaryanalysisofarandomisedplacebocontrolledmulticentreantimalarialtrial AT hasanzaima theheterogeneityofsymptomreportingacrossstudysitesasecondaryanalysisofarandomisedplacebocontrolledmulticentreantimalarialtrial AT ekawatill theheterogeneityofsymptomreportingacrossstudysitesasecondaryanalysisofarandomisedplacebocontrolledmulticentreantimalarialtrial AT woyessaa theheterogeneityofsymptomreportingacrossstudysitesasecondaryanalysisofarandomisedplacebocontrolledmulticentreantimalarialtrial AT teferit theheterogeneityofsymptomreportingacrossstudysitesasecondaryanalysisofarandomisedplacebocontrolledmulticentreantimalarialtrial AT waithiran theheterogeneityofsymptomreportingacrossstudysitesasecondaryanalysisofarandomisedplacebocontrolledmulticentreantimalarialtrial AT taylorwrj theheterogeneityofsymptomreportingacrossstudysitesasecondaryanalysisofarandomisedplacebocontrolledmulticentreantimalarialtrial AT leyb theheterogeneityofsymptomreportingacrossstudysitesasecondaryanalysisofarandomisedplacebocontrolledmulticentreantimalarialtrial AT dondorpa theheterogeneityofsymptomreportingacrossstudysitesasecondaryanalysisofarandomisedplacebocontrolledmulticentreantimalarialtrial AT bairdjk theheterogeneityofsymptomreportingacrossstudysitesasecondaryanalysisofarandomisedplacebocontrolledmulticentreantimalarialtrial AT whitenj theheterogeneityofsymptomreportingacrossstudysitesasecondaryanalysisofarandomisedplacebocontrolledmulticentreantimalarialtrial AT daynp theheterogeneityofsymptomreportingacrossstudysitesasecondaryanalysisofarandomisedplacebocontrolledmulticentreantimalarialtrial AT pricern theheterogeneityofsymptomreportingacrossstudysitesasecondaryanalysisofarandomisedplacebocontrolledmulticentreantimalarialtrial AT simpsonja theheterogeneityofsymptomreportingacrossstudysitesasecondaryanalysisofarandomisedplacebocontrolledmulticentreantimalarialtrial AT vonseidleinl theheterogeneityofsymptomreportingacrossstudysitesasecondaryanalysisofarandomisedplacebocontrolledmulticentreantimalarialtrial AT thriemerk heterogeneityofsymptomreportingacrossstudysitesasecondaryanalysisofarandomisedplacebocontrolledmulticentreantimalarialtrial AT commonsrj heterogeneityofsymptomreportingacrossstudysitesasecondaryanalysisofarandomisedplacebocontrolledmulticentreantimalarialtrial AT rajasekharm heterogeneityofsymptomreportingacrossstudysitesasecondaryanalysisofarandomisedplacebocontrolledmulticentreantimalarialtrial AT degagats heterogeneityofsymptomreportingacrossstudysitesasecondaryanalysisofarandomisedplacebocontrolledmulticentreantimalarialtrial AT chandk heterogeneityofsymptomreportingacrossstudysitesasecondaryanalysisofarandomisedplacebocontrolledmulticentreantimalarialtrial AT chaunh heterogeneityofsymptomreportingacrossstudysitesasecondaryanalysisofarandomisedplacebocontrolledmulticentreantimalarialtrial AT assefaa heterogeneityofsymptomreportingacrossstudysitesasecondaryanalysisofarandomisedplacebocontrolledmulticentreantimalarialtrial AT naddimmn heterogeneityofsymptomreportingacrossstudysitesasecondaryanalysisofarandomisedplacebocontrolledmulticentreantimalarialtrial AT pasaribuap heterogeneityofsymptomreportingacrossstudysitesasecondaryanalysisofarandomisedplacebocontrolledmulticentreantimalarialtrial AT rahimag heterogeneityofsymptomreportingacrossstudysitesasecondaryanalysisofarandomisedplacebocontrolledmulticentreantimalarialtrial AT sutantoi heterogeneityofsymptomreportingacrossstudysitesasecondaryanalysisofarandomisedplacebocontrolledmulticentreantimalarialtrial AT hientt heterogeneityofsymptomreportingacrossstudysitesasecondaryanalysisofarandomisedplacebocontrolledmulticentreantimalarialtrial AT hailua heterogeneityofsymptomreportingacrossstudysitesasecondaryanalysisofarandomisedplacebocontrolledmulticentreantimalarialtrial AT hasanzaima heterogeneityofsymptomreportingacrossstudysitesasecondaryanalysisofarandomisedplacebocontrolledmulticentreantimalarialtrial AT ekawatill heterogeneityofsymptomreportingacrossstudysitesasecondaryanalysisofarandomisedplacebocontrolledmulticentreantimalarialtrial AT woyessaa heterogeneityofsymptomreportingacrossstudysitesasecondaryanalysisofarandomisedplacebocontrolledmulticentreantimalarialtrial AT teferit heterogeneityofsymptomreportingacrossstudysitesasecondaryanalysisofarandomisedplacebocontrolledmulticentreantimalarialtrial AT waithiran heterogeneityofsymptomreportingacrossstudysitesasecondaryanalysisofarandomisedplacebocontrolledmulticentreantimalarialtrial AT taylorwrj heterogeneityofsymptomreportingacrossstudysitesasecondaryanalysisofarandomisedplacebocontrolledmulticentreantimalarialtrial AT leyb heterogeneityofsymptomreportingacrossstudysitesasecondaryanalysisofarandomisedplacebocontrolledmulticentreantimalarialtrial AT dondorpa heterogeneityofsymptomreportingacrossstudysitesasecondaryanalysisofarandomisedplacebocontrolledmulticentreantimalarialtrial AT bairdjk heterogeneityofsymptomreportingacrossstudysitesasecondaryanalysisofarandomisedplacebocontrolledmulticentreantimalarialtrial AT whitenj heterogeneityofsymptomreportingacrossstudysitesasecondaryanalysisofarandomisedplacebocontrolledmulticentreantimalarialtrial AT daynp heterogeneityofsymptomreportingacrossstudysitesasecondaryanalysisofarandomisedplacebocontrolledmulticentreantimalarialtrial AT pricern heterogeneityofsymptomreportingacrossstudysitesasecondaryanalysisofarandomisedplacebocontrolledmulticentreantimalarialtrial AT simpsonja heterogeneityofsymptomreportingacrossstudysitesasecondaryanalysisofarandomisedplacebocontrolledmulticentreantimalarialtrial AT vonseidleinl heterogeneityofsymptomreportingacrossstudysitesasecondaryanalysisofarandomisedplacebocontrolledmulticentreantimalarialtrial |