A systematic review of safety data reporting in clinical trials of vaccines against malaria, tuberculosis, and human immunodeficiency virus

Tamminga, Cindy; Kavanaugh, Michael; Fedders, Charlotte; Maiolatesi, Santina; Abraham, Neethu; Bonhoeffer, Jan; Heininger, Ulrich; Vásquez, Carlos; Moorthy, Vasee; Epstein, Judith E.; Richie, Thomas L.

doi:10.1016/j.vaccine.2013.01.045

Cited by 7 publications

(9 citation statements)

References 9 publications

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“…Standardisation of safety reporting across multiple sites in developing countries was borne out in a systematic review of safety data reporting in vaccine trials for malaria, tuberculosis and HIV, which focused partly on methods used to collect and report side effects. [6] This review noted imprecision and inconsistency of body temperature reporting, which is a key objective safety parameter. [6] While both the hardcopy and Unstructured Supplementary Services Data (USSD) tools are subject to transcription errors for temperature assessments by participants, only the latter allows for a contemporaneous alert to the research site of overtly incorrect readings.…”

Section: Vaccine Uptake and Efficacymentioning

confidence: 99%

“…[6] This review noted imprecision and inconsistency of body temperature reporting, which is a key objective safety parameter. [6] While both the hardcopy and Unstructured Supplementary Services Data (USSD) tools are subject to transcription errors for temperature assessments by participants, only the latter allows for a contemporaneous alert to the research site of overtly incorrect readings. The proper collection and documentation of unexpected side effects also allows regulators and sponsors alike, to link uncommon side effects across trials and sites, enabling the identification of sporadic, serious side effects.…”

Section: Vaccine Uptake and Efficacymentioning

confidence: 99%

“…The proper collection and documentation of unexpected side effects also allows regulators and sponsors alike, to link uncommon side effects across trials and sites, enabling the identification of sporadic, serious side effects. [6] The USSD also facilitates contemporaneous alerts to the site of other unexpected events, facilitating real time follow-up.…”

Section: Vaccine Uptake and Efficacymentioning

confidence: 99%

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(pMOTAR): A Pilot Study of Mobile Technology to Assess Reactogenicity (Preprint)

Mngadi¹,

Maharaj²,

Duki³

et al. 2017

Preprint

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BACKGROUND Accurate safety monitoring in HIV vaccine trials is vital to eventual licensure and consequent uptake of products. Current practice is to capture related side effects in a hardcopy tool, reconciled post vaccination, which is time-consuming, laborious and fraught with error. Unstructured Supplementary Service Data (USSD), commonly used to purchase airtime, has been suggested for collection of safety data in vaccine trials. With saturated access to mobile phones in South Africa, this cheap, accessible tool, may improve accuracy and completeness of collected data, and prove feasible and acceptable over the hardcopy tool. OBJECTIVE To develop and implement an USSD tool for real time safety data collection, that is feasible and acceptable to participants and staff, allowing for a completeness and accuracy comparison with the hardcopy tool. METHODS This pilot study of Mobile Technology to Assess Reactogenicity (pMOTAR) is being conducted at a single study site in South Africa enrolling participants in a phase 1/2a preventive HIV vaccine trial, as an open-label, randomised controlled trial, to all consenting HVTN 108 participants who continue to receive vaccinations. Participants are randomised 1: 1 to the hardcopy or USSD tool, with data collection targeted to the 3rd and 4th injections in the parent trial. Online feasibility and acceptability surveys will be completed by staff and participants at the post-vaccination visit. Error rates between the hardcopy tool and the USSD print-out and associated documentation will be itemised and compared. We hypothesize that the USSD tool will be shown to be feasible and acceptable to staff and participants and to have superior quality and completion rates to the hardcopy tool. RESULTS The study has received regulatory approval. The USSD tool has been designed and developed to include all the data fields required for reactogenicity reporting. Online feasibility and accessibility surveys in both languages have been successfully installed on a tablet. The study has been initiated. CONCLUSIONS Several HIV preventive vaccine trials are currently active in Southern Africa, making tools to improve efficiencies and minimise error necessary. Our results will help to determine if the USSD tool can be used in future vaccine studies and eventual roll out.

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Section: Vaccine Uptake and Efficacymentioning

confidence: 99%

Section: Vaccine Uptake and Efficacymentioning

confidence: 99%

Section: Vaccine Uptake and Efficacymentioning

confidence: 99%

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(pMOTAR): A Pilot Study of Mobile Technology to Assess Reactogenicity (Preprint)

Mngadi¹,

Maharaj²,

Duki³

et al. 2017

Preprint

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“…Drug safety assessment in randomized controlled trials (RCTs) is integral in development of comprehensive drug safety profile. Recently, there is enhanced quality on clinical trial reporting of safety outcomes through adherence to the Consolidated Standards of Reporting Trials (CONSORT) guideline (1,2). However, there is scant literature on standardized way to statistically analyse the safety outcomes in clinical trials.…”

Section: Introductionmentioning

confidence: 99%

Systematic review of statistical methods for safety data in malaria chemoprevention in pregnancy trials

Patson

Mukaka²,

Otwombe

et al. 2020

Preprint

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Background Drug safety assessments in clinical trials present unique analytical challenges. Some of these include adjusting for individual follow-up time, repeated measurements of multiple outcomes and missing data among others. Furthermore, pre-specifying appropriate analysis becomes difficult as some safety endpoints are unexpected. Although existing guidelines such as CONSORT encourage thorough reporting of adverse events (AEs) in clinical trials, they provide limited details for safety data analysis. The limited guidelines may influence suboptimal analysis by failing to account for some analysis challenges above. A typical example where such challenges exist are trials of antimalarial drugs for malaria prevention during pregnancy. Lack of proper standardized evaluation of the safety of antimalarial drugs has limited the ability to draw conclusions about safety. We have therefore conducted a systematic review to establish the current practice in statistical analysis for antimalarial drug safety in pregnancy. Methods We searched PubMed, Embase, Scopus, Malaria in Pregnancy Library and Cochrane Central Register of Controlled Trials for original English articles reporting Phase III (randomized controlled trials) RCTs on antimalarial drugs for malaria prevention in pregnancy published from January 2010 to July 2019. Results Eighteen trials were included in this review that collected multiple longitudinal safety outcomes including AEs. Statistical analysis and reporting of the safety outcomes in all the trials used descriptive statistics; proportions/counts (n=18, 100%) and mean/median (n=2, 11.1%). Results presentation included tabular (n=16, 88.9%) and text description (n=2, 11.1%). Univariate inferential methods were reported in most trials (n=16, 88.9%); including Chi-square/Fisher`s exact test (n=12, 66.7%), t-test (n=2, 11.1%) and Mann-Whitney/Wilcoxon test (n=1, 5.6%). Multivariable methods, including Poisson and negative binomial were reported in few trials (n=4, 22.2%). Assessment of a potential link between missing efficacy data and safety outcomes was not reported in any of the trials that reported efficacy missing data (n=7, 38.9%). Conclusion The review demonstrated that statistical analysis of safety data in antimalarial drugs for malarial chemoprevention in pregnancy RCTs are inadequate. The analysis insufficiently account for multiple safety outcomes potential dependence, follow-up time and informative missing data which can compromise antimalarial drug safety evidence development, based on the available data.

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“…guidance on clinical trial reporting of safety outcomes through adherence to the Consolidated Standards of Reporting Trials (CONSORT) guidelines [1,2]. However, there is scant literature on standardized ways to statistically analyse the safety outcomes in clinical trials.…”

mentioning

confidence: 99%

Systematic review of statistical methods for safety data in malaria chemoprevention in pregnancy trials

Patson

Mukaka

Otwombe

et al. 2020

Malar J

View full text Add to dashboard Cite

Background: Drug safety assessments in clinical trials present unique analytical challenges. Some of these include adjusting for individual follow-up time, repeated measurements of multiple outcomes and missing data among others. Furthermore, pre-specifying appropriate analysis becomes difficult as some safety endpoints are unexpected. Although existing guidelines such as CONSORT encourage thorough reporting of adverse events (AEs) in clinical trials, they provide limited details for safety data analysis. The limited guidelines may influence suboptimal analysis by failing to account for some analysis challenges above. A typical example where such challenges exist are trials of anti-malarial drugs for malaria prevention during pregnancy. Lack of proper standardized evaluation of the safety of antimalarial drugs has limited the ability to draw conclusions about safety. Therefore, a systematic review was conducted to establish the current practice in statistical analysis for preventive antimalarial drug safety in pregnancy.Results: Eighteen trials were included in this review that collected multiple longitudinal safety outcomes including AEs. Statistical analysis and reporting of the safety outcomes in all the trials used descriptive statistics; proportions/ counts (n = 18, 100%) and mean/median (n = 2, 11.1%). Results presentation included tabular (n = 16, 88.9%) and text description (n = 2, 11.1%). Univariate inferential methods were reported in most trials (n = 16, 88.9%); including Chi square/Fisher's exact test (n = 12, 66.7%), t test (n = 2, 11.1%) and Mann-Whitney/Wilcoxon test (n = 1, 5.6%). Multivariable methods, including Poisson and negative binomial were reported in few trials (n = 3, 16.7%). Assessment of a potential link between missing efficacy data and safety outcomes was not reported in any of the trials that reported efficacy missing data (n = 7, 38.9%). Conclusion:The review demonstrated that statistical analysis of safety data in anti-malarial drugs for malarial chemoprevention in pregnancy RCTs is inadequate. The analyses insufficiently account for multiple safety outcomes potential dependence, follow-up time and informative missing data which can compromise anti-malarial drug safety evidence development, based on the available data.

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A systematic review of safety data reporting in clinical trials of vaccines against malaria, tuberculosis, and human immunodeficiency virus

Cited by 7 publications

References 9 publications

(pMOTAR): A Pilot Study of Mobile Technology to Assess Reactogenicity (Preprint)

(pMOTAR): A Pilot Study of Mobile Technology to Assess Reactogenicity (Preprint)

Systematic review of statistical methods for safety data in malaria chemoprevention in pregnancy trials

Systematic review of statistical methods for safety data in malaria chemoprevention in pregnancy trials

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