the south african medical research council AWS
Sharing of Investigational Drug Among Participants in the VOICE Trial Jeeva Moodley1, Leanne Vallabhjee1, Sarita Naidoo1, Jayajothi Moodley1, Gita Ramjee1,2 1. HIV Prevention Research Unit, Medical Research Council, Westville, Durban, South Africa 2. Department of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, UK
Background
Results
Discussion/Conclusions
• In randomized placebo controlled trials effective preservation of the random allocation of treatment interventions is important for effective outcomes. A major challenge impacting the outcome of PrEP trials is adherence to study product. Adherence depends on participants using products consistently as instructed. • In MTN-003 (VOICE), a multi-site, randomized, placebo-controlled clinical trial studying the safety and efficacy of oral and topical PrEP for HIV prevention, adherence to study products was low. • Product sharing has been identified as a factor affecting adherence in clinical trials. Currently there is limited data on product sharing incidents in clinical trials. More data around product sharing is required to better understand its impact in clinical trials. • In the VOICE trial conducted at the MRC sites in Durban (7 sites: Tongaat, Verulam, Botha’s Hill, Chatsworth, Overport, Isipingo and Umkomaas), product sharing was identified by site pharmacists.
Product Discrepancies • Amongst 2750 women enrolled at the Durban sites, a total of 32 incidents of product sharing were identified by pharmacists: • Eighteen incidents (56%) involved participants returning products not assigned to them. • Fourteen incidents (44%) of possible product sharing were identified based on product count discrepancies and discussions with participants. Sources of Product Sharing • From participant reports, the main source of product sharing identified involved women residing in the same household with participants, 20/32 incidents (63%) (Figure 1). • Participants also reported that visitors (4 incidents) had access to their study products. • Other sources identified included co-workers who had access to study product (1 incident), participants travelling together (1 incident) and altruistic reasons (2 incidents). • In 4 cases, the source of product sharing could not be identified. • Product sharing occurred across all 7 MRC Durban sites (Figure 2). • Topical gels were more commonly shared than oral tablets (72% vs. 28%, respectively). • Strategies implemented included tailored messaging and unique identifiers to assist participants with easierFigure identification of their study products. 1. Sources of product sharing
• Interviews conducted with participants provided valuable insight into their living conditions, which people had access to their product and product use challenges. • From these interviews, it was established that participants most commonly shared product with sisters, cousins and friends living in the same house. • In some cases participants reported living together with women also enrolled in the VOICE trial. • Study gels were more commonly shared than oral tablets possibly due to gel applicators being used topically and easier to use compared to ingesting oral tablets. • The labelling of individual applicators with a unique sticker together with product identification messages was an innovation by pharmacists which helped prevent recurrences of product sharing from the same participant. • Pill and applicator counts play an important role in identifying possible product sharing incidents in PrEP trials. To minimize the impact of product sharing in clinical trials, early identification is critical and strategies need to be developed to address product use challenges. • Clear messaging on the correct use and return of study products needs to be consistently provided to participants. Thus pharmacist counselling will play an important role in the future roll out of PrEP trials.
Objectives • To describe incidents of product sharing across 7 MRC clinical research sites in Durban (Tongaat, Verulam, Botha’s Hill, Chatsworth, Overport, Isipingo, Umkomaas) and the strategies implemented to avert such occurrences.
3% 3%
Methods
6%
We would like to thank all the women who participated in the VOICE Trial and VOICE study teams at the South African Medical Research Council, HIV Prevention Research Unit (Durban). The Microbicide Trials Network is funded by the National Institute of Allergy and Infectious Diseases (UM1AI068633, UM1AI068615, UM1AI106707), with co-funding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Institute of Mental Health, all components of the U.S. National Institutes of Health.
12%
63%
13%
Co-workers Altruistic reasons Unknown
Travelling together Friends visiting Living together (friends and family)
Figure 1. Sources of product sharing Figure 2. Number of product sharing incidents by site 8 7
7
6 No. of incidents
Randomization • The Durban sites enrolled a total of 2750 women; 1647 and 1103 participants were randomized to the oral and gel arms, respectively. • Women were randomly assigned to tenofovir 1% gel or placebo gel, oral tenofovir (TDF), oral Truvada (TDF/FTC) or oral placebo. Dispensing of Study Product • At enrolment, participants on the oral arm were dispensed 30 tablets each of TDF and TDF/FTC to be taken orally once daily. Participants on the gel arm were dispensed 30 tenofovir gel applicators to be inserted intravaginally once daily. • Participants were counselled to return unused study product to Pharmacy at every visit. • For follow up visits, participants were provided with a 30-day supply to last until their next visit. If participants could not attend their next visit, they were dispensed more than their monthly allocation. Study Product Assessments • Product use assessments, pill and applicator counts were conducted by pharmacists at each monthly visit. A reconciliation of all product dispensed to and returned by participants was done. Unique participant identifiers and product specific codes were also checked to verify that the correct product was returned by participants. • Participant interviews were conducted by pharmacists when discrepancies were found with product assessments. • Counselling with product sharing messaging was provided to all participants who were eligible for product use.
Acknowledgements
6
5 4
5
Tongaat
Umkomaas
VOICE study products
4
3 2
5
3 2
1 0 Overport
Chatsworth
Verulam
Isipingo
Botha's Hill
Figure 2. Number of product sharing incidents by site
THE SOUTH AFRICAN MEDICAL RESEARCH COUNCIL Jeeva HPRU Poster R5.indd 1
2014/10/22 11:53 AM
Background
Results
Discussion/Conclusions
• In randomized placebo controlled trials effective preservation of the random allocation of treatment interventions is important for effective outcomes. A major challenge impacting the outcome of PrEP trials is adherence to study product. Adherence depends on participants using products consistently as instructed. • In MTN-003 (VOICE), a multi-site, randomized, placebo-controlled clinical trial studying the safety and efficacy of oral and topical PrEP for HIV prevention, adherence to study products was low. • Product sharing has been identified as a factor affecting adherence in clinical trials. Currently there is limited data on product sharing incidents in clinical trials. More data around product sharing is required to better understand its impact in clinical trials. • In the VOICE trial conducted at the MRC sites in Durban (7 sites: Tongaat, Verulam, Botha’s Hill, Chatsworth, Overport, Isipingo and Umkomaas), product sharing was identified by site pharmacists.
Product Discrepancies • Amongst 2750 women enrolled at the Durban sites, a total of 32 incidents of product sharing were identified by pharmacists: • Eighteen incidents (56%) involved participants returning products not assigned to them. • Fourteen incidents (44%) of possible product sharing were identified based on product count discrepancies and discussions with participants. Sources of Product Sharing • From participant reports, the main source of product sharing identified involved women residing in the same household with participants, 20/32 incidents (63%) (Figure 1). • Participants also reported that visitors (4 incidents) had access to their study products. • Other sources identified included co-workers who had access to study product (1 incident), participants travelling together (1 incident) and altruistic reasons (2 incidents). • In 4 cases, the source of product sharing could not be identified. • Product sharing occurred across all 7 MRC Durban sites (Figure 2). • Topical gels were more commonly shared than oral tablets (72% vs. 28%, respectively). • Strategies implemented included tailored messaging and unique identifiers to assist participants with easierFigure identification of their study products. 1. Sources of product sharing
• Interviews conducted with participants provided valuable insight into their living conditions, which people had access to their product and product use challenges. • From these interviews, it was established that participants most commonly shared product with sisters, cousins and friends living in the same house. • In some cases participants reported living together with women also enrolled in the VOICE trial. • Study gels were more commonly shared than oral tablets possibly due to gel applicators being used topically and easier to use compared to ingesting oral tablets. • The labelling of individual applicators with a unique sticker together with product identification messages was an innovation by pharmacists which helped prevent recurrences of product sharing from the same participant. • Pill and applicator counts play an important role in identifying possible product sharing incidents in PrEP trials. To minimize the impact of product sharing in clinical trials, early identification is critical and strategies need to be developed to address product use challenges. • Clear messaging on the correct use and return of study products needs to be consistently provided to participants. Thus pharmacist counselling will play an important role in the future roll out of PrEP trials.
Objectives • To describe incidents of product sharing across 7 MRC clinical research sites in Durban (Tongaat, Verulam, Botha’s Hill, Chatsworth, Overport, Isipingo, Umkomaas) and the strategies implemented to avert such occurrences.
3% 3%
Methods
6%
We would like to thank all the women who participated in the VOICE Trial and VOICE study teams at the South African Medical Research Council, HIV Prevention Research Unit (Durban). The Microbicide Trials Network is funded by the National Institute of Allergy and Infectious Diseases (UM1AI068633, UM1AI068615, UM1AI106707), with co-funding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Institute of Mental Health, all components of the U.S. National Institutes of Health.
12%
63%
13%
Co-workers Altruistic reasons Unknown
Travelling together Friends visiting Living together (friends and family)
Figure 1. Sources of product sharing Figure 2. Number of product sharing incidents by site 8 7
7
6 No. of incidents
Randomization • The Durban sites enrolled a total of 2750 women; 1647 and 1103 participants were randomized to the oral and gel arms, respectively. • Women were randomly assigned to tenofovir 1% gel or placebo gel, oral tenofovir (TDF), oral Truvada (TDF/FTC) or oral placebo. Dispensing of Study Product • At enrolment, participants on the oral arm were dispensed 30 tablets each of TDF and TDF/FTC to be taken orally once daily. Participants on the gel arm were dispensed 30 tenofovir gel applicators to be inserted intravaginally once daily. • Participants were counselled to return unused study product to Pharmacy at every visit. • For follow up visits, participants were provided with a 30-day supply to last until their next visit. If participants could not attend their next visit, they were dispensed more than their monthly allocation. Study Product Assessments • Product use assessments, pill and applicator counts were conducted by pharmacists at each monthly visit. A reconciliation of all product dispensed to and returned by participants was done. Unique participant identifiers and product specific codes were also checked to verify that the correct product was returned by participants. • Participant interviews were conducted by pharmacists when discrepancies were found with product assessments. • Counselling with product sharing messaging was provided to all participants who were eligible for product use.
Acknowledgements
6
5 4
5
Tongaat
Umkomaas
VOICE study products
4
3 2
5
3 2
1 0 Overport
Chatsworth
Verulam
Isipingo
Botha's Hill
Figure 2. Number of product sharing incidents by site
THE SOUTH AFRICAN MEDICAL RESEARCH COUNCIL Jeeva HPRU Poster R5.indd 1
2014/10/22 11:53 AM
