Randomised controlled trials in Africa of HIV and AIDS: descriptive study and spatial distribution.
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ABSTRACT: Objectives
To identify and describe randomised controlled trials on HIV and AIDS conducted in Africa and to map their spatial distribution using exact geographic coordinates.Design
Construction and analysis of a database of trials conducted wholly or partly in Africa and reported before 2004.Data sources
CENTRAL, Medline, Embase, and LILACS.Results
Our comprehensive search yielded 284 distinct records that were potentially eligible for inclusion in the database. Of these, 150 articles reported on 77 eligible trials published or reported from 1987 to 2003. Seven trials were identified exclusively from the CENTRAL database. Trials were conducted in 18 of 48 countries in sub-Saharan Africa. None were conducted in north Africa. Only 19 had a principal investigator located in an African country. Forty two trials assessed prevention and 35 assessed treatment. Most studies were funded by government agencies outside Africa (n = 43), with the pharmaceutical industry providing partial support to 16 of these. The pharmaceutical industry provided full or partial support to a further 18 trials. Only 43 trials reported conducting a power calculation for determining sample size. There was no mention of ethical approval or informed consent in 19 and 17 trials, respectively.Conclusion
The relatively small number of HIV/AIDS trials conducted in Africa is not commensurate with the burden of disease. Geographical mapping as an adjunct to prospective trial registration is a useful tool for researchers and decision makers to track existing and future trials.
SUBMITTER: Siegfried N
PROVIDER: S-EPMC1239977 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:IntroductionTo effectively address HIV/AIDS in Africa, evidence on preventing new infections and providing effective treatment is needed. Ideally, decisions on which interventions are effective should be based on evidence from randomized controlled trials (RCTs). Our previous research described African RCTs of HIV/AIDS reported between 1987 and 2003. This study updates that analysis with RCTs published between 2004 and 2008.ObjectivesTo describe RCTs of HIV/AIDS conducted in Africa and reported between 2004 and 2008.MethodsWe searched the Cochrane HIV/AIDS Specialized Register in September 2009. Two researchers independently evaluated studies for inclusion and extracted data using standardized forms. Details included location of trials, interventions, methodological quality, location of principal investigators and funders.ResultsOur search identified 834 RCTs, with 68 conducted in Africa. Forty-three assessed prevention-interventions and 25 treatment-interventions. Fifteen of the 43 prevention RCTs focused on preventing mother-to-child HIV transmission. Thirteen of the 25 treatment trials focused on opportunistic infections. Trials were conducted in 16 countries with most in South Africa (20), Zambia (12) and Zimbabwe (9). The median sample size was 628 (range 33-9645). Methods used for the generation of the allocation sequence and allocation concealment were adequate in 38 and 32 trials, respectively, and 58 reports included a CONSORT recommended flow diagram. Twenty-nine principal investigators resided in the United States of America (USA) and 18 were from African countries. Trials were co-funded by different agencies with most of the funding obtained from USA governmental and non-governmental agencies. Nineteen pharmaceutical companies provided partial funding to 15 RCTs and African agencies co-funded 17 RCTs. Ethical approval was reported in 65 trials and informed consent in 61 trials.ConclusionPrevention trials dominate the trial landscape in Africa. Of note, few principal investigators and funders are from Africa. These findings mirror our previous work and continue to indicate a need for strengthening trial research capacity in Africa.
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Project description:The purpose of this article is to describe lessons from the first lymphoma clinical trial conducted by the AIDS Malignancy Consortium (AMC) in sub-Saharan Africa (SSA). AMC-068 was a randomized phase II comparison of intravenous versus oral chemotherapy for HIV-positive diffuse large B-cell lymphoma. Opening in 2016, AMC-068 planned to enroll 90 patients (45 per arm) in Kenya, Malawi, Uganda, and Zimbabwe over 24 months and follow patients for 24 months to assess overall survival. In 2018, the study closed after screening 42 patients but enrolling only 7. Challenges occurred during protocol development, pre-activation, and postactivation. During protocol development (2011-2012), major obstacles were limited baseline data to inform study design; lack of consensus among investigators and approving bodies regarding appropriateness of the oral regimen and need for randomized comparison with cyclophosphamide, doxorubicin, vincristine, and prednisone; and heterogeneity across sites in local standards for diagnosis, staging, and treatment. During pre-activation (2012-2016), challenges included unexpected length and layers of regulatory approval across multiple countries, need to upgrade pathology capacity at sites, need to augment existing chemotherapy infusion capacity at sites, and procurement issues for drugs and supplies. Finally, during postactivation (2016-2018), challenges included long delays between symptom onset and screening entry for many patients, leading to compromised performance status and organ function; other patient characteristics that frequently led to exclusion, including high tumor proliferative index or other pathologic features that were disallowed; and costs of routine diagnostic procedures often being borne by patients, which also contributed to pre-enrollment delays. Lessons from AMC-068 are being applied to the design and conduct of new AMC lymphoma trials in SSA, and the study has contributed to a strong operational foundation that will support innovative clinical trials in the future.
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Project description:BackgroundNine out of ten deaths from malaria occur in sub-Saharan Africa. Various control measures have achieved some progress in the control of the disease, but malaria is still a major public health problem in Africa. Randomized controlled trials (RCTs) are universally considered the best study type to rigorously assess whether an intervention is effective. The study reported here provides a descriptive analysis of RCTs reporting interventions for the prevention and treatment of malaria conducted in Africa, with the aim of providing detailed information on their main clinical and methodological characteristics, that could be used by researchers and policy makers to help plan future research.MethodsSystematic searches for malaria RCTs were conducted using electronic databases (Medline, Embase, the Cochrane Library), and an African geographic search filter to identify RCTs conducted in Africa was applied. Results were exported to the statistical package STATA 8 to obtain a random sample from the overall data set. Final analysis of trial characteristics was done in a double blinded fashion by two authors using a standardized data extraction form.ResultsA random sample of 92 confirmed RCTs (from a total of 943 reports obtained between 1948 and 2007) was prepared. Most trials investigated drug treatment in children with uncomplicated malaria. Few trials reported on treatment of severe malaria or on interventions in pregnant women. Most trials were of medium size (100-500 participants), individually randomized and based in a single centre. Reporting of trial quality was variable. Although three-quarter of trials provided information on participants' informed consent and ethics approval, more details are needed.ConclusionsThe majority of malaria RCT conducted in Africa report on drug treatment and prevention in children; there is need for more research done in pregnant women. Sources of funding, informed consent and trial quality were often poorly reported. Overall, clearer reporting of trials is needed.
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Project description:ObjectivesTo explore stakeholders' perceptions of decision aids designed to support the informed consent decision-making process for randomised controlled trials.DesignQualitative semistructured interviews. Participants were provided with prototype trial decision aids in advance to stimulate discussion. Interviews were analysed using an established interpretive approach.Participants23 stakeholders: Trial Managers (n=5); Research Nurses (n=5); Ethics Committee Chairs (n=5); patients (n=4) and Clinical Principal Investigators (n=4).SettingEmbedded within two ongoing randomised controlled trials. All interviews conducted with UK-based participants.ResultsCertain key aspects (eg, values clarification exercises, presentation of probabilities, experiences of others and balance of options) in the prototype decision aids were perceived by all stakeholders as having a significant advantage (over existing patient information leaflets) in terms of supporting well informed appropriate decisions. However, there were some important differences between the stakeholder groups on specific content (eg, language used in the section on positive and negative features of taking part in a trial and the overall length of the trial decision aids). Generally the stakeholders believed trial decision aids have the potential to better engage potential participants in the decision-making process and allow them to make more personally relevant decisions about their participation.ConclusionsCompared to existing patient information leaflets, stakeholders perceived decision aids for trial participation to have the potential to promote a more 'informed' decision-making process. Further efforts to develop, refine and formally evaluate trial decision aids should be explored.
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Project description:HIV/AIDS is associated with significant morbidity, mortality, and financial burden. For these reasons, robust clinical evidence is critical. We aim to investigate the fragility index, fragility quotient, and risk of bias of clinical trial endpoints in HIV medicine. The fragility index represents the minimum amount of trial endpoint "nonevents" changed to "events" in one trial arm required to nullify statistical significance. The fragility quotient contextualized the fragility index by dividing the index by the total trial sample size. We selected eligible trials from the Department of Health and Human Services guideline for the use of antiretroviral agents in HIV-1-infected adults and adolescents. We calculated the fragility index and fragility quotient for all included trials. The Cochrane "risk of bias" Tool 2.0 was used to evaluate the likelihood and sources of bias in the included trials. Thirty-nine RCTs were included for our analysis of fragility. Thirty-six were included for our analysis of the risk of bias. The median fragility index was 5. Three RCTs were at high risk of bias, all due to the selection of the endpoint or statistical test. Twenty had some concerns for risk of bias. The analyzed HIV medicine RCT endpoints were fragile, overall. This indicates that a median of 5 patients across all included studies would nullify the statistical significance of the endpoints. Furthermore, we found evidence that concerns for bias are present at a high rate.
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Project description:ObjectivesTo describe the characteristics of randomised controlled trials supported by the main non-commercial sources of funding in the United Kingdom between 1980 and 2002.DesignDescriptive survey.SettingRandomised controlled trials funded by the Medical Research Council, NHS research and development programme, Department of Health, Chief Scientist Office in Scotland, and medical research charities.Participants1464 randomised controlled trials supported by the main non-commercial sources of funding.ResultsSupport for randomised controlled trials by the main sources of non-commercial funding in the United Kingdom has fallen in recent years, without any concomitant increase in the sample sizes of these studies. Drug trials in a limited range of health problems have dominated among the studies supported by the Medical Research Council and medical research charities. Until recently, the NHS research and development programme supported randomised controlled trials of various healthcare interventions, in a wide range of health problems, but between 1999 and 2002 many of the subprogrammes that had commissioned trials were discontinued.ConclusionsThe future of non-commercial randomised controlled trials in the United Kingdom has been threatened by the discontinuation or demise of national and regional NHS research and development programmes. Support also seems to be declining from the Medical Research Council and the medical research charities. It is unclear what the future holds for randomised controlled trials that address issues of no interest to industry but are of great importance to patients and practitioners.
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Project description:BackgroundWith 7.7 million South Africans currently infected with human immunodeficiency virus (HIV) and 4.8 million currently receiving antiretroviral treatment (ART), the epidemic represents a considerable burden for the country's resource-limited health system. In response to the health and human resource shortages, task shifting to community health workers (CHWs) and empowering people living with HIV (PLWH) are integral parts of a sustainable ART strategy. Despite the success of the ART programme, South Africa still faces both prevention and treatment challenges. To tackle these challenges, future endeavours need to focus on the role played by the households of PLWH in mediating between the community and PLWH themselves. Building health-enabling "HIV competent" households with the capacity to actively stimulate lifestyles that foster health, offers a potential strategy to tackle South Africa's HIV-related challenges. The aim of the "Sinako: Households and HIV" study is to investigate to what extent and how an intervention can increase HIV competence in PLWH and their households, and subsequently optimise the impact of CHW support on individual ART outcomes.MethodsThe "Sinako" study is a cluster-randomised controlled trial with two arms. In the control arm, CHWs offer a standard package of support to PLWH during home visits, focused on the individual. The intervention arm includes both a focus on the individual and the household to enable the patient to self-manage their treatment within an HIV competent household. A longitudinal mixed methods design is adopted to analyse the data. For the quantitative data analysis, methods including latent cross-lagged modelling, multilevel modelling and logistic regression will be used. To assess the acceptability and feasibility of the intervention and to construct a comprehensive picture of the mechanisms underlying the impact on the household and the PLWH, qualitative data (in-depth interviews and focus group discussions) will be collected and analysed.DiscussionStimulating HIV competence in households could be a feasible and sustainable strategy to optimise the outcomes of CHW interventions and thus be important for HIV treatment interventions in resource-limited settings.Trial registrationPan African Clinical Trial Registry, PACTR201906476052236. Registered on 24 June 2019.
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Project description:INTRODUCTION:In some randomised trials, the primary interest is in the mechanisms by which an intervention exerts its effects on health outcomes. That is, clinicians and policy-makers may be interested in how the intervention works (or why it does not work) through hypothesised causal mechanisms. In this article, we highlight the value of understanding causal mechanisms in randomised trials by applying causal mediation analysis to two randomised trials of complex interventions. MAIN BODY:In the first example, we examine a potential mechanism by which an exercise programme for rheumatoid arthritis of the hand could improve hand function. In the second example, we explore why a rehabilitation programme for ankle fractures failed to improve lower-limb function through hypothesised mechanisms. We outline critical assumptions that are required for making valid causal inferences from these analyses, and provide results of sensitivity analyses that are used to assess the degree to which the estimated causal mediation effects could have been biased by residual confounding. CONCLUSION:This paper demonstrates how the application of causal mediation analyses to randomised trials can identify the mechanisms by which complex interventions exert their effects. We discuss methodological issues and assumptions that should be considered when mediation analyses of randomised trials are used to inform clinical practice and policy decisions.
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Project description:BackgroundPoor recruitment to randomised controlled trials (RCTs) is a widespread and important problem. With poor recruitment being such an important issue with respect to the conduct of randomised trials, a systematic review of controlled trials on recruitment methods was undertaken in order to identify strategies that are effective.MethodsWe searched the register of trials in Cochrane library from 1996 to end of 2004. We also searched Web of Science for 2004. Additional trials were identified from personal knowledge. Included studies had to use random allocation and participants had to be allocated to different methods of recruitment to a 'real' randomised trial. Trials that randomised participants to 'mock' trials and trials of recruitment to non-randomised studies (e.g., case control studies) were excluded. Information on the study design, intervention and control, and number of patients recruited was extracted by the 2 authors.ResultsWe identified 14 papers describing 20 different interventions. Effective interventions included: telephone reminders; questionnaire inclusion; monetary incentives; using an 'open' rather than placebo design; and making trial materials culturally sensitive.ConclusionFew trials have been undertaken to test interventions to improve trial recruitment. There is an urgent need for more RCTs of recruitment strategies.
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Project description:To evaluate the efficacy and safety of modafinil in the treatment of fatigue in patients with human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) and to assess effect on depressive symptoms.Patients who were HIV+ and had clinically significant fatigue (according to the Fatigue Severity Scale [FSS]) were included in a 4-week randomized, placebo-controlled, double-blind trial. This was followed by an additional 8 weeks of open-label treatment for modafinil responders and 12 weeks for placebo nonresponders. The primary outcome measure for fatigue and depression was the Clinical Global Impressions-Improvement scale, supplemented by the FSS, Hamilton Depression Rating Scale, and Beck Depression Inventory. Safety was assessed with assays of CD4 cell count and HIV ribonucleic acid (RNA) viral load. Visits were weekly for 4 weeks, then biweekly, with a follow-up visit at 6 months. Maximum trial dose of modafinil was 200 mg/d. Data for this study were collected between December 2004 and December 2008.115 patients were randomly assigned. In intention-to-treat analyses, fatigue response rate to modafinil was 73% and to placebo, 28%. Attrition was 9%. Modafinil did not have an effect on mood alone in the absence of improved energy. At week 4, CD4 cell counts did not change significantly; HIV RNA viral load showed a trend decline for patients taking modafinil but not for those taking placebo. At 6 months, those still taking modafinil had more energy and fewer depressive symptoms than patients who were not taking modafinil, and only those still taking modafinil showed a significant decline from baseline in their HIV RNA viral load.Modafinil appears to be effective and well tolerated in treating fatigue in HIV+ patients. Consideration of its use is warranted considering the high prevalence of fatigue in the HIV community, its minimal side effects, and overall patient acceptance.clinicaltrials.gov Identifier: NCT00118378.
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