Quality Assurance in Clinical Trials Requiring Radiation Therapy in Sub-Saharan Africa.

PURPOSE: Given the increasing availability of radiation therapy in sub-Saharan Africa, clinical trials that include radiation therapy are likely to grow. Ensuring appropriate delivery of radiation therapy through rigorous quality assurance is an important component of clinical trial execution. We reviewed the process for credentialing radiation therapy sites and radiation therapy quality assurance through the Imaging and Radiation Oncology Core (IROC) Houston Quality Assurance Center for AIDS Malignancy Consortium (AMC)-081, a multicenter study of cisplatin and radiation therapy for women with locally advanced cervical cancer living with HIV, conducted by the AIDS Malignancy Consortium at 2 sites in South Africa and Zimbabwe. METHODS AND MATERIALS: Women living with HIV with newly diagnosed stage IB2, IIA (>4 cm), IIB-IVA cervical carcinoma (per the 2009 International Federation of Gynecology and Obstetrics [FIGO] staging classifications) were enrolled in AMC-081. They received 3-dimensional conformal external beam radiation therapy (EBRT) to the pelvis (41.4-45 Gy) using a linear accelerator, high-dose-rate brachytherapy (6-9 Gy to point A with each fraction and up to 4 fractions), and concurrent weekly cisplatin (40 mg/m2). IROC reviewed EBRT and brachytherapy quality assurance records after treatment. RESULTS: All of the 38 women enrolled in AMC-081 received ±5% of the protocol-specified prescribed dose of EBRT. Geometry of brachytherapy applicator placement was scored as per protocol in all implants. Doses to points A and B, International Commission on Radiation Units and Measurements (ICRU) bladder, or ICRU rectum required correction by IROC in >50% of the implants. In the final evaluation, 58% of participants (n = 22) were treated per protocol, 40% (n = 15) had minor protocol deviations, and 3% (n = 1) had major protocol deviations. No records were received within 60 days of treatment completion as requested in the protocol. CONCLUSIONS: Major radiation therapy deviations were low, but timely submission of radiation therapy data did not occur. Future studies, especially those that include specialized radiation therapy techniques such as stereotactic or intensity-modulated radiation therapy, will require pathways to ensure timely and adequate quality assurance.

Challenges of HIV Lymphoma Clinical Trials in Africa: Lessons From the AIDS Malignancy Consortium 068 Study.

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.

Clinical Trials for Treatment and Prevention of HIV-Associated Malignancies in Sub-Saharan Africa: Building Capacity and Overcoming Barriers.

PURPOSE: The aim of this study was to review the current status of clinical trials for HIV-associated malignancies in people living with HIV in sub-Saharan Africa (SSA) and efforts made by the AIDS Malignancy Consortium (AMC) to build capacity in SSA for HIV malignancy research. METHODS: All malignancy-related clinical trials in 49 SSA countries on ClinicalTrials.gov were reviewed and evaluated for inclusion and exclusion criteria pertaining to HIV status. Additional studies by AMC in SSA were compiled from Web-based resources, and narrative summaries were prepared to highlight AMC capacity building and training initiatives. RESULTS: Of 96 cancer trials identified in SSA, only 11 focused specifically on people living with HIV, including studies in Kaposi sarcoma, cervical dysplasia and cancer, non-Hodgkin lymphoma, and ocular surface squamous neoplasia. Recognizing the increasing cancer burden in the region, AMC expanded its clinical trial activities to SSA in 2010, with 4 trials completed to date and 6 others in progress or development, and has made ongoing investments in developing research infrastructure in the region. CONCLUSION: As the HIV-associated malignancy burden in SSA evolves, research into this domain has been limited. AMC, the only global HIV malignancy-focused research consortium, not only conducts vital HIV-associated malignancies research in SSA, but also develops pathology, personnel, and community-based infrastructure to meet these challenges in SSA. Nonetheless, there is an ongoing need to build on these efforts to improve HIV-associated malignancies outcomes in SSA.

Professionals with delivery skills: backbone of the health system and key to reaching the maternal health Millennium Development Goal.

The attainment of the fifth Millennium Development Goal requires adequate national reserves of skilled birth attendants. Nurses, midwives, and their equivalents form the frontline of the formal health system are a critical element of global efforts to reduce ill-health and poverty in the poorest areas of the world. Planning and policies supporting these cadres of workers must be placed high on the development agenda and championed by key international and national players. This article first sets forth an argument for the equity and efficiency of nurses, midwives, and their equivalents as the cadre largely responsible for maternal health. Second, it traces the root causes of neglect of this critical cadre, including a vacuum in political will in the context of poverty, lack of protections for frontline workers, the historical political position of the field of midwifery, lack of a pipeline of secondary school graduates, and gender inequity. Investment in the largely female cadre that cares for the majority of the world's poorer women has simply not been a high enough priority. Five key policy recommendations include harnessing political will and adequate metrics, protection of frontline workers' safety and livelihoods, ensuring an adequate pipeline with a focus on girls' education, donor support for training and professional organizations, and a rapid scale-up of a robust cadre of delivery care professionals. Finally, a call for unified international support of rapid scale-up of cadres of delivery care workers is put forth.

"Delivering" on the MDGs?: equity and maternal health in Ghana, Ethiopia and Kenya.

OBJECTIVES: The Millennium Development Goals (MIDGs) have put maternal health in the mainstream, but there is a need to go beyond the MDGs to address equity within countries. We argue that MDG focus on maternal health is necessary but not sufficient. This paper uses Demographic and Health Survey (DHS) data from Kenya, Ethiopia and Ghana to examine a set of maternal health indicators stratified along five different dimensions. The study highlights the interactive and multiple forms of disadvantage and demonstrates that equity monitoring for the MDGs is possible, even given current data limitations. METHODS: We analyse DHS data from Ghana, Kenya and Ethiopia on four indicators: skilled birth attendant, contraceptive prevalence rate, AIDS knowledge and access to a health facility. We define six social strata along five different dimensions: poverty status, education, region, ethnicity and the more traditional wealth quintile. Data are stratified singly (e.g. by region) and then stratified simultaneously (e.g. by region and by education) in order to examine the compounded effect of dual forms of vulnerability. RESULTS: Almost all disparities were found to be significant, although the stratifier with the strongest effect on health outcomes varied by indicator and by country. In some cases, urban-dwelling is a more significant advantage than wealth and in others, educational status trumps poverty status. The nuances of this analysis are important for policymaking processes aimed at reaching the MDGs and incorporating maternal health in national development plans. CONCLUSIONS: The article highlights the following key points about inequities and maternal health: 1) measuring and monitoring inequity in access to maternal health is possible even in low resource settings-using current data 2) statistically significant health gaps exist not just between rich and poor, but across other population groups as well, and multiple forms of disadvantage confer greater risk and 3) policies must be aligned with reducing health gaps in access to key maternal health services.

Setting the stage for equity-sensitive monitoring of the maternal and child health Millennium Development Goals.

OBJECTIVE: This analysis seeks to set the stage for equity-sensitive monitoring of the health-related Millennium Development Goals (MDGs). METHODS: We use data from international household-level surveys (Demographic and Health Surveys (DHS) and Multiple Indicator Cluster Surveys (MICS)) to demonstrate that establishing an equity baseline is necessary and feasible, even in low-income and data-poor countries. We assess data from six countries using 11 health indicators and six social stratifiers. Simple bivariate stratification is complemented by simultaneous stratification to expose the compound effect of multiple forms of vulnerability. FINDINGS: The data reveal that inequities are complex and interactive: inferences cannot be drawn about the nature or extent of inequities in health outcomes from a single stratifier or indicator. CONCLUSION: The MDGs and other development initiatives must become more comprehensive and explicit in their analysis and tracking of inequities. The design of policies to narrow health gaps must take into account country-specific inequities.

A district-based audit of the causes and circumstances of maternal deaths in South Kalimantan, Indonesia.

A district-based audit of maternal and perinatal mortality began during 1994 in three provinces of South Kalimantan, Indonesia. Both medical and non-medical factors were documented and an effort was made to progress from merely assessing substandard care to recommending improvements in access to care and the quality of care. Extensive discussions of cases of maternal death were held during regular meetings with providers, policy-makers and community members. The sources of information included verbal autopsies with family members and medical records. Between 1995 and 1999 the audit reviewed 130 maternal deaths. The leading causes of death were haemorrhage (41%) and hypertensive diseases (32%). Delays in decision-making and poor quality of care in health facilities were seen as contributory factors in 77% and 60% of the deaths, respectively. Economic constraints were believed to have contributed to 37% of the deaths. The distance between a patient's home and a health provider or facility did not appear to have a significant influence, nor did transport problems. The audit led to changes in the quality of obstetric care in the district. Its success was particularly attributable to the process of accountability of both health providers and policy-makers and to improved working relationships between health providers at different levels and between providers and the community. With a view to the continuation and further expansion of the audit it may be necessary to reconsider the role of the provincial team, the need of health providers for confidentiality, the added benefit of facility-based audits, the need to incorporate scientific evidence into the review process, and the possible consideration of severe complications as well as deaths. It may also be necessary to recognize that village midwives are not solely responsible for maternal deaths.