Decision making in a clinical trial for a life-threatening illness: Therapeutic expectation, not misconception

Lawrence, David; Ssali, Agnes; Moshashane, Neo; Nabaggala, Georgina; Maphane, Lebogang; Harrison, Thomas S.; Meya, David B.; Jarvis, Joseph N; Seeley, Janet

doi:10.1016/j.socscimed.2022.115082

Cited by 6 publications

(4 citation statements)

References 40 publications

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“…Increasingly more persons with HIV-CM are ART-experienced globally, suggesting that ART alone is not sufficient to eliminate the incidence of HIV-CM 12,13,23,26,34 . Lack of knowledge about cryptococcal meningitis among the general population results in lumbar puncture refusal, and a low index of suspicion among healthcare providers leads to delays in cryptococcal diagnosis, with a negative impact on outcomes 214 . A study in rural Uganda showed that 70% of patients who died following a HIV-CM diagnosis had sought care >3 times before the diagnosis was made.…”

Section: [H1] Outlookmentioning

confidence: 99%

Cryptococcal meningitis

Tugume,

Ssebambulidde,

Kasibante

et al. 2023

Nat Rev Dis Primers

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Cryptococcus neoformans and Cryptococcus gattii species complexes cause meningoencephalitis with high fatality rates and considerable morbidity, particularly in persons with deficient T cell mediated immunity, most commonly affecting people living with HIV. Whereas the global incidence of HIV-associated cryptococcal meningitis (HIV-CM) has decreased over the past decade, cryptococcosis still accounts for one in five AIDSrelated deaths globally due to the persistent burden of advanced HIV disease. Moreover, mortality remains high (~50%) in low resource settings. The armamentarium to decrease cryptococcosis-associated mortality is expanding: cryptococcal antigen (CrAg) screening in the serum and pre-emptive azole therapy for cryptococcal antigenemia are well established, whereas enhanced pre-emptive combination treatment regimens to improve survival of persons with cryptococcal antigenemia are under trials. Short course ( 7 days) amphotericin-based regimens combined with flucytosine are currently the preferred options for induction therapy of cryptococcal meningitis. Whether short course induction regimens improve long term morbidity such as depression, reduced neurocognitive performance and physical disability among survivors is subject to further study. Here, we discuss underlying immunology, changing epidemiology, and updates on management of cryptococcal meningitis with emphasis on HIV-associated disease.

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Section: [H1] Outlookmentioning

confidence: 99%

Cryptococcal meningitis

Tugume,

Ssebambulidde,

Kasibante

et al. 2023

Nat Rev Dis Primers

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“…As a result, we found that the decision to enrol in the trial was predominantly motivated by fear of death, an acknowledgment that the trial was their best chance of survival, and trust in the research teams. This subject has been discussed in more detail elsewhere [25]. The levels of comprehension around the trial For two trial participants who were decision-disorientated it was not possible to conduct an interview with a surrogate decision-maker due to logistical barriers.…”

Section: The Perspective Of Participantsmentioning

confidence: 99%

The acceptability of the AMBITION-cm treatment regimen for HIV-associated cryptococcal meningitis: Findings from a qualitative methods study of participants and researchers in Botswana and Uganda

et al. 2022

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Background The AMBITION-cm trial for HIV-associated cryptococcal meningitis demonstrated that a single, high-dose of liposomal amphotericin (AmBisome) plus 14-days of oral flucytosine and fluconazole was non-inferior in terms of all-cause mortality to 7-days of amphotericin B deoxycholate and flucytosine followed by 7-days of fluconazole (Control). The AmBisome regimen was associated with fewer adverse events. We explored the acceptability of the AmBisome regimen from the perspective of participants and providers. Methods We embedded a qualitative methods study within the AMBITION-cm sites in Botswana and Uganda. We conducted in-depth interviews with trial participants, surrogate decision makers, and researchers and combined these with direct observations. Interviews were transcribed, translated, and analysed thematically. Results We interviewed 38 trial participants, 20 surrogate decision makers, and 31 researchers. Participant understanding of the trial was limited; however, there was a preference for the AmBisome regimen due to the single intravenous dose and fewer side effects. More time was required to prepare the single AmBisome dose but this was felt to be acceptable given subsequent reductions in workload. The AmBisome regimen was reported to be associated with fewer episodes of rigors and thrombophlebitis and a reduction in the number of intravenous cannulae required. Less intensive monitoring and management was required for participants in the AmBisome arm. Conclusions The AmBisome regimen was highly acceptable, being simpler to administer despite the initial time investment required. The regimen was well tolerated and associated with less toxicity and resultant management. Widespread implementation would reduce the clinical workload of healthcare workers caring for patients with HIV-associated cryptococcal meningitis.

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“…Enrolment may offer the best possible outcome for socially vulnerable participants and be an active choice, in expectation of better care. 5 As such, researchers should take adequate measures to mitigate the effects of socioeconomic vulnerability, by promoting quality healthcare and addressing participants’ therapeutic expectations based on their specific (health) needs. 6 7 According to the Council for International Organisations of Medical Sciences, offering medical care that goes beyond the scope of a scientific study—also referred to as ancillary care (AC)—should not be considered an undue influence to participate in research.…”

Section: Introductionmentioning

confidence: 99%

An ancillary care policy in a vaccine trial conducted in a resource-constrained setting: evaluation and policy recommendations

Lemey,

Larivière,

Osang'ir

et al. 2024

BMJ Glob Health

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IntroductionClear guidelines to implement ancillary care (AC) in clinical trials conducted in resource-constrained settings are lacking. Here, we evaluate an AC policy developed for a vaccine trial in the Democratic Republic of the Congo and formulate policy recommendations.MethodsTo evaluate the AC policy, we performed a longitudinal cohort study, nested in an open-label, single-centre, randomised Ebola vaccine trial conducted among healthcare personnel. Participants’ demographic information, residence distance to the study site and details on the financial and/or medical support provided for any (serious) adverse events ((S)AE) were combined and analysed. To assess the feasibility of the AC policy, an expenditure analysis of the costs related to AC support outcomes was performed.ResultsEnrolment in this evaluation study started on 29 November 2021. The study lasted 11 months and included 655 participants from the Ebola vaccine trial. In total, 393 participants used the AC policy, mostly for AE management (703 AE and 94 SAE) via medication provided by the study pharmacy (75.3%). Men had a 35.2% (95% CI 4.0% to 56.6%) lower likelihood of reporting AE compared with women. Likewise, this was 32.3% lower (95% CI 5.8% to 51.4%) for facility-based compared with community-based healthcare providers. The daily AE reporting was 78.8% lower during the passive vs the active trial stage, and 97.4% lower during unscheduled vs scheduled visits (p<0.001). Participants living further than 10 km from the trial site more frequently reported the travel distance as a reason for not using the policy (p<0.04). In practice, only 1.1% of the operational trial budget was used for AC policy support.ConclusionThe trial design, study population and local health system impacted the use of the AC policy. Nonetheless, the AC policy implementation in this remote and resource-constrained setting was feasible, had negligible budgetary implications and contributed to participants’ healthcare options and well-being.

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Decision making in a clinical trial for a life-threatening illness: Therapeutic expectation, not misconception

Cited by 6 publications

References 40 publications

Cryptococcal meningitis

Cryptococcal meningitis

The acceptability of the AMBITION-cm treatment regimen for HIV-associated cryptococcal meningitis: Findings from a qualitative methods study of participants and researchers in Botswana and Uganda

An ancillary care policy in a vaccine trial conducted in a resource-constrained setting: evaluation and policy recommendations

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