Development of a direct ADR reporting tool for patients to address under-reporting of ADRs to the National Pharmacovigilance Unit in South Africa

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dc.contributor.advisorPage, Carineen_ZA
dc.contributor.advisorAllen, Elizabethen_ZA
dc.contributor.advisorReuter, Helmuthen_ZA
dc.contributor.authorMaluleke, Tirhani Linethen_ZA
dc.contributor.otherFaculty of Medicine and Health Sciences. Dept. of Medicine. Division of Clinical Pharmacology.en_ZA
dc.date.accessioned2022-11-23T06:33:17Zen_ZA
dc.date.accessioned2023-01-16T12:41:28Zen_ZA
dc.date.available2022-11-23T06:33:17Zen_ZA
dc.date.available2023-01-16T12:41:28Zen_ZA
dc.date.issued2022-12en_ZA
dc.descriptionThesis (PhD) -- Stellenbosch University, 2022.en_ZA
dc.description.abstractENGLISH ABSTRACT: High standards of public health can be achieved through efficient and safe utilisation of healthcare products and the continuous monitoring thereof. Pharmacovigilance (PV), defined as the science and activities relating to the monitoring of adverse reactions associated with all medicines, is however hampered by the global under-reporting of adverse drug reactions (ADRs) by healthcare professionals. Several countries have successfully incorporated direct patient reporting into their PV system as a means of addressing the under-reporting challenge. Innovative ADR reporting tools have the potential to enable PV systems through increasing signal detection, assessment, understanding and prevention of adverse effects. Whilst the proof-of-concept of such tools have been promising, the use thereof by patients and consumers with access to the South African healthcare system has not been tested. The aim of the current study is to develop an ADR reporting tool for use by consumers in reporting ADRs to address under-reporting in South Africa. The design of the current study and the development of a patient/consumer ADR reporting tool precedes the adoption and implementation of the Med Safety Mobile Application as an online Adverse Event Following Immunisation (AEFI) reporting tool by the South African Health Products Regulatory Authority (SAHPRA) in 2021. If it had not been for the outbreak of the COVID-19 pandemic in 2020 and the immediate need for AEFI reporting tools following the global roll-out of immunisation programmes shortly thereafter by the World Health Organisation (WHO), National Health Departments and Regulators around the globe, this study would have been one of the first to have investigated direct consumer reporting on a larger scale in South Africa. The standard South African Health Products Regulatory Authority (SAHPRA) Yellow Form was used as a frame reference for designing an online-based consumer ADR reporting tool, which is compatible with a mobile application and a paper-based version. Validation and reliability testing of the tool was carried out in two stages: A content validation by healthcare professionals determined whether the content of the tool is appropriate and relevant for the designed purpose of ADR reporting by consumers/patients and face validation by consumers evaluated the usability of the tool in terms of readability, how clear/easy to follow the instructions and/or provide the required information. The developed and tested ADR reporting tool consists of five main elements: consumer’s details, consumer’s medical history, ADR details, suspected medicine(s), and reporter details. All items included received a majority inter-agreement rating of over 80% each as relevant to include in the tool, except for the reporter initials, the batch number and expiry date of the suspected medicine. Using the McNemar Chi-square test, the test and re-test responses of face validation showed no significant difference in responses across all items in the ADR reporting tool. Feasibility testing to assess the ease with which the ADR reporting tool could be used, how practical it is to access the tool and submit the report through it was carried out over a period of 1 year and 3 months. Participants were recruited from twelve healthcare centres and through social media, and they have completed and submitted ADR reports via online tool. A total of 348 reports were received with female consumers contributing 58.3% most of which were from those aged 31- 40 years (22.5%). These were associated with birth control medicines, the fourth highest suspected medicines reported (13.5%) with all reported ADRs listed as expected in the respective package inserts. Hydrochlorothiazide (52.17%) and enalapril (27.54%) were the most frequently suspected medicines within the antihypertensive class. All suspected medicines had well-established safety profiles, except for a lamivudine, tenofovir disoproxil fumarate and dolutegravir fixed-dose combination, nine reports related to investigational medicinal products and twenty-three suspected medicines which could not be identified. Expectedness of reported ADRs was confirmed in 73.9% of the suspected medicines, with dose reduction in 3.4%, treatment changed in 1.8% and treatment stopped in 6.9% of the consumers. A total of 5.3% of suspected medicines could not be verified as the names could not be recognised. Only two reports were received from healthcare professionals with the completeness and terminology used being similar to those of non-healthcare professionals. Reported terms produced 63.4% ‘exact matches’ from the MedDRA search, 8.7% were from ‘contains search’ results and terms used from ‘lexicant variant’ results amounted to 2.5%. Over 25% of the reported terms could not be found in the MedDRA database and therefore an alternative term was used. The high response rate in this study as well as the manner in which the consumers completed the ADR reports demonstrates their understanding and feasibility of using the tool to consistently submit ADR reports whose information would enable causality assessment over time, which will also boost the local PV system. However, the use of English only in the study limited participation of consumers who cannot use and/or understand the language. There was also no measure on the readability index conducted and causality assessment was not carried out. With consumer reporting being relatively new in South Africa, this study can be used as a basis to assess and improve on the newly introduced SAHPRA ADR reporting tools. Further studies are needed to assess the interest, understanding and factors influencing consumers to report ADRs.en_ZA
dc.description.abstractAFRIKAANS OPSOMMING: ‘n Publieke gesondheidstelsel van hoë standaard is haalbaar deur die effektiewe en veilige gebruik van gesondheidsprodukte, asook die voortdurende monitering daarvan. Farmakowaaksaamheid (FW), wat gedefinieer word as die wetenskap van aktiwiteite wat veband hou met die monitering van nadelige medisyne reaksies (NMRs), geassosieer met alle medisyne, word egter belemmer deur die wêreldwye tekort aan verslagdoening van dié reaksies, deur gesondheidsdeskundiges. Baie lande het reeds, as ‘n poging tot die aanspreking van die uitdagings ten opsigte van ‘n tekort aan verslagdoening, die direkte rapportering van NMRs deur pasiënte tot hul FW sisteme, in plek gestel. Innoverende hulpmiddelle en toepassings vir NMR verslagdoening het die potensiaal om FW sisteme te versterk deur verhoogde sein waarneming, assessering, en kennis en voorkoming van nadelige medisyne reaksies. Terwyl die bewys-van-konsep van hierdie hulpmiddelle en toepassings belowend blyk te wees, is die gebruik daarvan deur pasiënte en verbruikers met toegang tot die Suid-Afrikaanse gesondheidstelsel, nog nie getoets nie. Die doel van hierdie studie is om ‘n NMR rapporterings-toepassing te ontwikkel wat deur verbruikers ingespan kan word om die tekort aan verslagdoening in Suid-Afrika aan te spreek. Die ontwerp van die huidige studie en die ontwikkeling van ‘n pasiënt/verbruiker NMR-aanmeldingshulpmiddel gaan die aanvaarding en implementering van die Med Safety Mobile Application vooras as ‘n aanlyn Adverse Event Following Immunisation (AEFI)-verslagdoeningsinstrument deur die Suid-Afrikaanse Gesondheidsprodukte Regulatoriese Agentskap (SAGPRA) in 2021. As dit nie was vir die uitbreek van die COVID-19 pandemie in 2020 en die onmiddellike behoefte aan AEFI-verslagdoeningsinstrumente na die wêreldwye uitrol van immuniseringsprogramme kort daarna dear die Wêreldgesondheidorganisasie (WGO), Nasionale Gesondheid Departemente en Reguleerders regoor die wereld, sou hierdie studie een van die eerstes gewees het wat direkte verbruikerverslaggewing op ‘n groter skaal in Suid-Afrika ondersoek het. Die standaard Geel Vorm van die Suid-Afrikaanse Gesondheidsprodukte Regulatoriese Agentskap (SAGPRA) is gebruik as ’n raamverwysing vir die ontwerp van ’n aanlyn-gebasseerde rapporterings-toepassing vir verbruikers, wat verenigbaar is met ’n selfoontoep en ’n papiergebasseerde weergawe van die toepassing. Validasie- en betroubaarheidstoetsing van die toepassing is in twee fases uitgevoer: ‘n inhoudvalidasie deur gesondheidsdeskundiges het bepaal of die inhoud van die toepassing toepaslik en relevant is vir die ontwerpte doel van NMR verslagdoening deur verbruikers/pasiënte; aangesigsvalidasie deur verbruikers het die bruikbaarheid van die toepassing, ten opsigte van leesbaarheid en die duidelikheid en verstaanbaarheid van die instruksies en/of die weergee van die verwagte inligting, geëvalueer. Die ontwikkelde en getoetsde toepassing vir NMR aanmelding bestaan uit vyf hoofelemente: verbruiker se inligting, verbruiker se mediese geskiedenis, NMR inligting, vermoedelike verwante medisyne(s) en die aanmelder se inligting. Alle items wat ingesluit is, het elk ‘n meerderheids-inter-ooreenkoms-gradeing van meer as 80% ontvang, as relevant tot die insluiting daarvan in die toepassing, behalwe vir die aanmelder se voorletters, en die lotnommer en vervaldatum van die verdagte medisyne. Deur die McNemar Chi-square toets te gebruik, het die toets en hertoets response van die aangesigsvalidasie geen betekenisvolle verskil in die response oor alle items heen in die NMR toepassing gewys nie. Die lewensvatbaarheidstoetsing om die gemak waarmee die rapporterings-toepassing gebruik kan word, hoe prakties dit is om toegang daartoe te verkry en om ‘n verslag daarop in te dien, is oor ‘n tydperk van ‘n jaar en 3 maande uitgevoer. Deelnemers wat van twaalf gesondheidsentra en deur sosiale media gewerf is, het NMR verslae voltooi en via die aanlyn toepassing ingedien. ‘n Totaal van 348 verslae is ontvang met vroulike verbruikers wat 58.3% van die verslae ingedien het, die meeste van hulle was tussen 31- 40 jaar oud (22.5%). Hierdie verslae is geassosieer met geboortebeperkingsmiddels, die vierde hoogste verdagte medisyne wat gerapporteer is (13.5%), met al die gerapporteerde NMRs in die produkte se onderskeie voubiljette, gelys as verwagte newe-effekte. Hidrochloriedtiasied (52.17%) en enalapriel (27.54%) was die mees gereelde verdagte medisynes binne die hipertensiewe-middelklas, wat aangemeld is. Alle verdagte medisynes het goed gevestigde veiligheidsprofiele gehad, behalwe lamivudine, tenofovir disoproxil en dolutegravir vaste-dosis kombinasie, nege verslae wat geassosieer was met medisinale produkte wat nog ondersoek word en drie-en-twintig verdagte medisynes wat nie geidentifiseer kon word nie. Verwagtheid van aangemelde NMRs is bevestig in 73.9% van die verdagte medisynes, met ‘n dosisvermindering in 3.4%, verandering in behandeling (1.8%) of staking van behandeling (6.9%). ‘n Totaal van 5.3% van verdagte medisynes kon nie geverifieer word nie, aangesien die name daarvan nie herken kon word nie. Slegs twee verslae is van gesondheidsdeskundiges ontvang met inligting, soortgelyk aan dit wat deur nie- gesondheidsdeskundiges verskaf is. Van die aangemelde NMR-terme het 63.4% presiese ooreenkomste met die soekterme in MedDRA getoon, 8.7% het soekterme bevat en 2.5% was van “leksikante variante”. Meer as 25% van die aangemelde terme kon nie in die MedDRA databasis opgespoor word nie. ’n Alternatiewe term is in sulke gevalle gebruik. Die hoë responstempo in hierdie studie asook die manier waarop die verbruikers die NMR verslae voltooi het, demonstreer hulle begrip ten opsigte van die gebruik van die toepassing, asook die lewensvatbaarheid van die toepassing ten einde dit gereeld te gebruik om NMR verslae in te dien. Dit sal oor tyd oorsaaklikheidsbepaling toelaat en ook die plaaslik PV sisteem verbeter. Met Engels egter as die enigste voertaal in die studie, was die deelname van verbruikers wat nie Engels magtig is nie, beperk. Daar is ook geen maatstaf op die leesbaarheidsindeks uitgevoer nie en oorsaaklikheidsbepaling is nie uitgevoer nie. Met verslagdoening deur verbruikers as ‘n betreklike nuwe metode in Suid-Afrika, kan hierdie studie aangewend word as ‘n platform om die Suid-Afrikaanse Gesondheidsprodukte Regulatoriese Agentskap (SAGPRA) se nuwe bekendstelling NMR aanmeldings-toepassing te assesseer en te verbeter.af_ZA
dc.description.versionDoctoralen_ZA
dc.format.extentxxiv, 152 pages : illustrationsen_ZA
dc.identifier.urihttp://hdl.handle.net/10019.1/125923en_ZA
dc.language.isoen_ZAen_ZA
dc.publisherStellenbosch : Stellenbosch Universityen_ZA
dc.rights.holderStellenbosch Universityen_ZA
dc.subjectPharmacovigilance -- South Africaen_ZA
dc.subjectDrugs -- Side effects -- South Africaen_ZA
dc.subjectPublic health administration -- South Africaen_ZA
dc.subjectHealth services administration -- South Africaen_ZA
dc.subjectMedical technology -- South Africaen_ZA
dc.subjectUCTDen_ZA
dc.titleDevelopment of a direct ADR reporting tool for patients to address under-reporting of ADRs to the National Pharmacovigilance Unit in South Africaen_ZA
dc.typeThesisen_ZA
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