Articles tagged as "Civil society and community responses / Resilience"

Civil society responses

Community Involvement in HIV and Tuberculosis Research

 

Harrington M. J Acquir. Immune Defic Syndr. 2009; Nov:52(S2)

 

Since advent of the HIV pandemic in the 1980s, affected communities and individuals living with HIV have played key roles in leading the response to the crisis. Achievements of the HIV treatment activist movement include persuading the US Food and Drug Administration to allow expanded access to experimental treatments for those unable to enter controlled clinical trials; accelerated approval of anti-HIV drugs based on surrogate markers such as CD4 cell and HIV RNA changes; and the involvement ofpeople with HIV and their advocates throughout the research system, including in the design, conduct, and evaluation of clinical trials. HIV treatment activists have adapted these skills to tackle tuberculosis (TB) research and programs. Considering the dearth of adequate diagnostic, treatment, and preventive interventions to control TB among people with HIV, the experiences and efforts of HIV activists are vital to accelerate research and development of new diagnostics, drugs, and vaccines to identify, cure, and prevent TB, especially among people living with HIV. Advocacy to implement World Health Organization collaborative HIV/TB activities and to reduce TB's toll among people with HIV provides a case study of how scale-up of HIV and TB programs contributes to health system strengthening.

 

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Editors’ note: This ‘must read’ article presents a succinct history of the HIV treatment activist movement, underscoring the informed and relentless pressure that accelerated the pace of research and development for novel antiretroviral drugs. Community activists used mass media and the internet, political lawsuits and legislation, public demonstrations and civil disobedience, and coalition-building and other strategies to influence both the speed and conduct of treatment research. The article describes the gains made and the challenges ahead, particularly for tuberculosis research. TB urgently requires new diagnostic methods (the ones in common use today date from the 19 th century), improved treatment drugs and programmes, and a new vaccine (Bacille Calmette-Guérin, the TB vaccine, was developed between 1908 and 1921). Among people living with HIV, TB is the commonest cause of death and over 1.4 million people living with HIV develop TB each year. Activists from among all stakeholders (community, scientists, government, funders, and others) need to join in concerted action to ensure rapid development of diagnostics, drugs, vaccines, and delivery systems to prevent people dying from tuberculosis .

 

 


 Increasing Civil Society Participation in the National HIV Response: The Role of UNGASS Reporting.

 

Peersman G, Ferguson L, Torres M, Smith S, Gruskin S. J Acquir Immune Defic Syndr. 2009 52(S2)

 

The 2001 Declaration of Commitment on HIV/AIDS provided impetus for strengthening collaboration between government and civil society partners in the HIV response. The biennial UNGASS reporting process is an opportunity for civil society to engage in a review of the implementation of commitments. The article is reporting on the descriptive analyses of the National Composite Policy Index from 135 countries; a debriefing on UNGASS reporting with civil society in 40 countries; and 3 country case studies on the UNGASS process. In the latest UNGASS reporting round, engagement of civil society occurred in the vast majority of countries. The utility of UNGASS reporting seemed to be better understood by both government and civil society, compared with previous reporting rounds. Civil society participation was strongest when civil society groupings took the initiative and organized themselves. An important barrier was their lack of experience with national level processes. Civil society involvement in national HIV planning and strategic processes was perceived to be good, but better access to funding and technical support is needed. Instances remain where there are fundamental differences between government and civil society perceptions of the HIV policy and program environment. How or whether differences were resolved is not always clear, but both government and civil society seemed to appreciate the opportunity for discussion. Collaborative reporting by government and civil society on UNGASS indicators is a small but potentially valuable step in what should be an ongoing and fully institutionalized process of collaborative planning, implementation, monitoring, assessment and correction of HIV responses. The momentum achieved through the UNGASS process should be maintained with follow-up actions to address data gaps, formalize partnerships and enhance active and meaningful engagement.

 

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Editors’ note: Civil society is defined in this article as voluntary associations of citizens that undertake actions in support of people living with or affected by HIV; it does not include the private (profit-making) or public (government) sectors. Civil society involvement in national HIV responses has increased since 2005 but there is room for improvement in virtually all countries if civil society participation is to be truly active and meaningful. One indicator is the number of ‘shadow reports’ from civil society groups dissatisfied with the government reporting on progress. This number has declined from 33 countries in 2006 to 15 countries in 2008, and some of the latter reports were simply providing additional information, as opposed to expressing dissenting views. Although UNGASS reporting is an international accountability tool based on the 2001 Declaration of Commitment, the reporting process itself can be a mechanism to increase civil society engagement in the national HIV response and enhance government accountability to its own citizens.

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Economics

HIV/AIDS, growth and poverty in KwaZulu-Natal and South Africa: an integrated survey, demographic and economy wide analysis.

Thurlow J, Gow J, George G. J Int AIDS Soc 2009;12:18.

This paper estimates the economic impact of HIV on the KwaZulu-Natal province and the rest of South Africa. Thurlow et al extended previous studies by employing: an integrated analytical framework that combined firm surveys of workers’ HIV prevalence by sector and occupation; a demographic model that produced both population and workforce projections; and a regionalized economy-wide model linked to a survey-based micro-simulation module. This framework permits a full macro-microeconomic assessment. Results indicate that HIV greatly reduces annual economic growth, mainly by lowering the long-run rate of technical change. However, impacts on income poverty are small, and inequality is reduced by HIV. This is because high unemployment among low-income households minimises the economic costs of increased mortality. By contrast, slower economic growth hurts higher income households despite lower HIV prevalence. They conclude that the increase in economic growth that results from addressing HIV is sufficient to offset the population pressure placed on income poverty. Moreover, incentives to mitigate HIV lie not only with poorer infected households, but also with uninfected higher income households. Their findings reveal the substantial burden that HIV places on future economic development in KwaZulu-Natal and South Africa, and confirms the need for policies to curb the economic costs of the pandemic.

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Editors’ note: This macro-microeconomic assessment of the present and future impact of HIV on the KwaZulu-Natal economy used survey data on HIV prevalence among managers, skilled workers, and labourers in 15 companies across four sectors: agriculture, manufacturing, tourism, and transport sectors. These findings were used to calibrate a demographic model and then its projections were imposed on a dynamic computable general equilibrium model linked to a household-survey based micro-simulation model. Sound complicated? Yes, it definitely is, however this approach integrating demographic, economy-wide, and survey-based models produces striking estimates. The Gross Domestic Product (GDP) growth rate in KwaZulu-Natal is lowered by 1.6% per year and although that does not sound like much, it results in an economy that would be 43% smaller in 2025 than it would be in the absence of HIV. These are the kinds of results that policy makers understand and that can motivate them to mobilise investments to curb HIV transmission and improve treatment access.

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Civil society responses

Challenge and co-operation: civil society activism for access to HIV treatment in Thailand.Ford N, Wilson D, Cawthorne P, Kumphitak A, Kasi-Sedapan S, Kaetkaew S, Teemanka S, Donmon B, Preuanbuapan C. Trop Med Int Health. 2009; 14: 258-66 .

 

Civil society has been a driving force behind efforts to increase access to treatment in Thailand. A focus on HIV medicines brought civil society and non-governmental and government actors together to fight for a single cause, creating a platform for joint action on practical issues to improve care for people with HIV within the public health system. The Thai Network of People with HIV/AIDS, in partnership with other actors, has provided concrete support for patients and for the health system as a whole; its efforts have contributed significantly to the availability of affordable generic medicines, early treatment for opportunistic infections, and an informed and responsible approach towards antiretroviral treatment that is critical to good adherence and treatment success. This change in perception of people living with HIV from ‘passive receiver’ to ‘co-provider’ of health care has led to improved acceptance and support within the healthcare system. Today, most people living with HIV in Thailand can access treatment, and efforts have shifted to supporting care for excluded populations.

 

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Editors’ note: This ‘participant-observers’ perspective, written by representatives of AIDS ACCESS Foundation, the Thai Network of People living with HIV (TNP+) and Médecins Sans Frontières, describes how civil society activism in Thailand pushed the government to increase availability of affordable antiretroviral drugs and then provided practical support to implementation of treatment programmes. Civil society groups played a pivotal role in Thailand’s decision to establish universal health care coverage for its citizens and used legal and other strategies to fight intellectual property restrictions to medicines, including non-HIV medicines. The groups represented by the co-authors developed a strategy for central involvement of trained people living with HIV in the scale up of treatment programmes through providing systematic peer support in ‘Comprehensive and Continuous Care Centres’ in hospitals. This rich historical analysis of policy change in Thailand is well worth the read.

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Household resilience

Household impacts of AIDS: using a life course analysis to identify effective, poverty-reducing interventions for prevention, tratment, and care. Loewenson R, Whiteside A, Hadingham J. Aids Care. 2009; 21:1032-1041

 

A life course approach was used to assess household level impacts and inform interventions around HIV risk and AIDS vulnerability across seven major age-related stages of life. The focus was sub-Saharan Africa. The authors provided a qualitative review of evidence from published literature, particularly multicountry reviews on impacts of AIDS, on determinants of risk and vulnerability, and reports of large surveys. Areas of potential stress from birth to old age in households affected by AIDS, and interventions for dealing with these specific stresses were identified. While specific interventions for HIV are important at different stages, achieving survival and development outcomes demands a wider set of health, social security, and development interventions. One way to determine the priorities amongst these actions is to give weighting to interventions that address factors that have latent impacts later in life, which interrupt accumulating risk, or that change pathways to reduce the risk of both immediate and later stress. This qualitative review suggests that interventions, important for life cycle transitions in generalized epidemics where HIV risk and AIDS vulnerability are high, lie within and outside the health sector, and suggests examples of such interventions.

Editors’ note: A life course concept views people as passing though various transitions and stages in life with events at one stage having effects at later stages. Points of stress in the life cycle that HIV can affect offer opportunities to influence pathways of accumulating vulnerability. These can range from the obvious example of preventing mother-to-child transmission by antiretroviral prophylaxis to broader interventions, such as promoting more open communication within families. HIV influences the number and quality of ‘buffers’ available to deal with stress, including the buffers of social support, financial resources, and good health. Household and individual resilience to shocks experienced in generalised epidemics can be supported through broader systems approaches within and beyond the health sector that help people to manage the interacting socioeconomic and health challenges of HIV. Examples include explicit interventions to strengthen social networks, increase spending on public services and community safety nets, introduce law reform and enforcement, invest in training and support for family carers, and increase access to education and employment opportunities.

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Trial conduct

Doab A, Topp L, Day CA, Dore GJ, Maher L. Clinical trial literacy among injecting drug users in Sydney, Australia: a pilot study. Contemp Clin Trials. 2009 Apr 16. [Epub ahead of print]

This pilot study examined knowledge, understanding and perceived acceptability of key methodological concepts in clinical trials among injecting drug users in Sydney, Australia. Participants were clinical trial-experienced (n=17) and trial-naïve (n=99) people who inject drugs who were recruited from community needle and syringe programs, and through institutions involved in clinical trials with injecting drug using participants.  Cross-sectional data were collected via a study-specific interviewer-administered survey. Following detailed verbal explanations, higher proportions of trial-experienced than trial-naïve participants demonstrated an understanding of all clinical trial concepts assessed, including single blinding (94% versus 60%); placebo (94% versus 49%); equipoise (71% versus 60%); comparison (59% versus 46%); randomisation (59% versus 21%); and double blinding (47% versus 3%).  Multivariate analyses indicated a better understanding among trial-experienced participants. Participants who demonstrated an understanding of ‘placebo’ and ‘double blinding’ were significantly more likely to perceive these concepts to be acceptable than those who did not. The results indicate the need for targeted education programs that adequately inform people who inject drugs about clinical trial concepts prior to recruitment to a clinical trial, and support adaptations of informed consent procedures to ensure trial participants’ comprehensive understanding of methodologies and their implications.

Editors’ note: Despite a generally good understanding of trial concepts among people who inject drugs, with those who had already participated in a trial unsurprisingly knowing more, the perceived acceptability of equipoise, placebo, and double blinding was only 55-60%. Given that future candidate hepatitis C and HIV vaccine trials will need to recruit and retain large numbers of injecting drug users, clinical trial literacy programmes are needed for this key population. Among the adaptations that could improve informed consent procedures would be considering them in the context of wider community engagement, with informed consent viewed as an ongoing process rather than simply a procedure at recruitment (cf UNAIDS/AVAC Good Participatory Practice Guidelines for Biomedical HIV Prevention Trials).

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Faith-based organisations

Rankin SH, Lindgren T, Kools SM, Schell E. The condom divide: disenfranchisement of Malawi women by church and state. J Obstet Gynecol Neonatal Nurs. 2008;37(5):596-604; quiz 604-6.

 

Rankin and colleagues examined the impact of 2 mitigating social institutions, religious organizations, and the state, on Malawi women’s vulnerability to HIV. In-depth interviews with a purposive sample of 40 central leaders from 5 faith-based organizations in Malawi were recorded and transcribed as part of an on-going larger study. Qualitative description was used to identify themes and categories. The study took place in primarily urban and periurban areas of south-central Malawi. A minimum of 6 leaders from each faith-based organization were interviewed; the mean age of the primarily male (68%) participants was 44 years (range 26-74). Analysis of religious leaders’ messages about HIV produced an overarching theme, the condom divide, which conceptualized the divergence between faith-based organizations and the state’s prevention messages related to HIV prevention strategies. The authors conclude that faith-based organizations have « demonized » state messages about condoms as promoting sin. The faith-based organizations’ insistence on abstinence and faithfulness leaves women with few options to protect themselves. As socially conscious citizens of the world, nurses can increase the responsiveness to the disparate levels of suffering and death in countries like Malawi.

Editors’ note: Whereas the Malawi government has broken the silence about sexual behaviours and their contributions to the HIV epidemic and is actively involved in HIV prevention, faith-based organisations in this country in which religion plays an important role are lagging behind. About 55% of the population is Protestant, 20% Catholic, and 15% Muslim, while 10% practice African traditional religions. This study of 40 religious leaders representing 5 faith-based organisations (3 mainstream Christian, 1 indigenous Pentecostal, and 1 Muslim) revealed that religious leaders, who are uniquely positioned to champion HIV prevention across Malawi, have largely refused or been reluctant to do so. Condoms are condemned except for discordant couples and there is little acknowledgement that the disadvantaged position of women along with double standards for sexual behaviour place women at heightened risk of HIV exposure. A human rights-public health approach that respects the right of everyone to sound scientific evidence to preserve health and encourages everyone to act responsibly would be a synergistic contribution that religious organisations could make now to the AIDS response in Malawi.

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Community-based HIV prevention

Cowan FM, Pascoe SJ, Langhaug LF, Dirawo J, Chidiya S, Jaffar S, Mbizvo M, Stephenson JM, Johnson AM, Power RM, Woelk G, Hayes RJ. The Regai Dzive Shiri Project: a cluster randomised controlled trial to determine the effectiveness of a multi-component community-based HIV prevention intervention for rural youth in Zimbabwe - study design and baseline results. Trop Med Int Health. Volume 13, Issue 10, Date: October 2008, Pages: 1235-1244.

Cowan et all set out to assess the effectiveness of a community-based HIV prevention intervention for adolescents in terms of its impact on (1) HIV and Herpes simplex virus type 2 (HSV-2) incidence and on rates of unintended pregnancy and (2) reported sexual behaviour, knowledge and attitudes. These were assessed through a cluster randomised trial of a multi-component HIV prevention intervention for adolescents based in rural Zimbabwe. Thirty communities were selected and randomised in 2003 to early or deferred intervention implementation. A baseline bio-behavioural survey was conducted among 6791 secondary school pupils (86% of eligibles) prior to intervention implementation. At baseline, prevalences were 0.8% (95% CI: 0.6-1.0) for HIV and 0.2% (95% CI: 0.1-0.3%) for HSV-2. Four girls (0.12%) were pregnant. There was excellent balance between study arms. Orphans who made up 35% of the cohort were at increased risk of HIV [ age-sex adjusted odds ratio 3.4 (95% CI: 1.7-6.5)]. 11.9% of young men and 2.9% of young women reported that they were sexually active (P < 0.001); however, there were inconsistencies in the sexual behaviour data. Girls were less likely to know about reproductive health issues than boys (P < 0.001) and were ). This is one of the first rigorous evaluations of a community-based HIV prevention intervention for young people in southern Africa. The low rates of HIV suggest that the intervention was started before this population became sexually active. Inconsistency and under-reporting of sexual behaviour re-emphasise the importance of using externally validated measures of sexual risk reduction in behavioural intervention studies.

Editors´note: This community-based HIV prevention trial targeting young people, their parents, and adults in the community to change individual behaviour, as well as societal and cultural norms about adolescent sexuality to reduce risk more broadly, will report results in Dakar at the ICASA conference next month. These baseline findings from 2003 reveal good balance between the study arms and low levels of HIV and herpes simplex virus 2 infection. A striking finding that emphasises the need to validate self-report of sexual behaviours is the fact that none of the four young women that were pregnant reported having had sexual intercourse.

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HIV in the workplace

Vaas JR. The role of HIV/AIDS committees in effective workplace governance of HIV/AIDS in South African small and medium-sized enterprises. SAHARA J. 2008;5(1):2-10.

 

The primary purpose of this study was to assess the role, status and scope of workplace AIDS committees as a means of effective workplace governance of AIDS impact, and their role in extending social protective HIV-related rights to employees. In-depth qualitative case studies were conducted in five South African small and medium-sized enterprises that were actively implementing HIV policies and programmes. Companies commonly implemented HIV policies and programmes through a workplace committee dedicated to HIV or a generic committee dealing with issues other than HIV. Management, through the human resources department and the occupational health practitioner often drove initial policy formulation, and had virtually sole control of the AIDS budget. Employee members of committees were mostly volunteers, and were often production or blue collar employees, while there was a notable lack of participation by white-collar employees, line management and trade unions. While the powers of workplace committees were largely consultative, employee committee members often managed in an indirect manner to secure and extend social protective rights on HIV to employees, and monitor their effective implementation in practice. In the interim, workplace committees represented one of the best means to facilitate more effective workplace HIV governance. However, the increased demands on collective bargaining as a result of an anticipated rises in HIV-related morbidity and mortality might prove to be beyond the scope of such voluntary committees in the longer term.

Editors’ note: With human resources and occupational health representatives predominating and little trade union involvement, these committees, that have done much to extend employee rights and social protection, are ill equipped to face more serious HIV-related issues. Employee representatives and shop stewards in these companies, some of which have HIV prevalence as high as 20%, need to ensure that collective bargaining agreements include training and policy information for shop stewards. Departments of Labour should be monitoring implementation of the code of good practice on HIV in businesses of all sizes.

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Resilience

Murphy DA, Marelich WD. Resiliency in young children whose mothers are living with HIV/AIDS. AIDS Care. 2008;20(3):284-91.

 

Resiliency was investigated among well children 6-11 years of age (N = 111) whose mothers were living with AIDS or were HIV symptomatic to determine if mother’s HIV status was a risk factor that could effect child resiliency, as well as to investigate other factors associated with resiliency. Assessments were conducted with mother and child dyads over four time points (baseline, 6-, 12-, and 18-month follow-ups). Maternal illness was a risk factor for resiliency: as maternal viral load increased, resiliency was found to decrease. Longitudinally, resilient children had lower levels of depressive symptoms (by both mother and child report). Resilient children also reported higher levels of satisfaction with coping self-efficacy. A majority of the children were classified as non-resilient; implications for improving resiliency among children of HIV-positive mothers are discussed.

Editors’ note: Resiliency at the individual level, as opposed to community resilience, refers to a person’s capacity for successful adaptation despite challenging circumstances. Rather than simply avoiding negative outcomes, resilience means demonstrating adequate adaptation in the presence of adversity. Resilient children have a more active approach to problem solving, tend to perceive experiences constructively, have better self-esteem, and have high self-reports of effectiveness. A strong adult attachment, problem solving and coping skills training, and psychotherapeutic interventions for depression can help build resiliency in vulnerable children.

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Trial design and conduct

Morin SF, Morfit S, Maiorana A, Aramrattana A, Goicochea P, Mutsambi JM, Robbins JL, Richards TA. Building community partnerships: case studies of Community Advisory Boards at research sites in Peru, Zimbabwe, and Thailand. Clin Trials. 2008;5(2):147-56.

Differences in resources, knowledge, and infrastructure between countries initiating and countries hosting HIV prevention research trials frequently yield ethical dilemmas. Community Advisory Boards have emerged as one strategy for establishing partnerships between researchers and host communities to promote community consultation in socially sensitive research. Morin and co-authors undertook to understand the evolution of Community Advisory Boards and community partnerships at international research sites conducting HIV prevention trials. Three research sites of the HIV Prevention Trials Network (HPTN) were selected to include geographical representation and diverse populations at risk for HIV exposure - Lima, Peru; Chitungwiza, Zimbabwe; and Chiang Mai, Thailand. Data collection included review of secondary data, including academic publications and site-specific progress reports; observations at the research sites; face-to-face interviews with Community Advisory Boards members, research staff, and other key informants; and focus groups with study participants. Rapid assessment techniques were used for data analysis. The authors found that two of the three Community Advisory Boards developed new strategies for community representation in response to new studies. All three Community Advisory Boards expanded their original function and became advocates for broader community interests beyond HIV prevention. The participation and input of community representatives, in response to critical incidents that occurred at the sites over the past five years, helped to solidify partnerships between researchers and communities. In terms of limitations the authors point out that Rapid Assessment is an exploratory methodology designed to provide an understanding of a situation based on the integration of multiple data sources, collected within a short period of time, without a formal examination of transcribed and coded data. Case studies, as a method, are meant to draw out what can be learned from a single case but are not, in the scientific sense, generalizable. They conclude that in developing countries, Community Advisory Boards can be dynamic entities that enhance the HIV research process, assist in responding to issues involving research ethics, and prepare communities for HIV research.

Editors´note: This assessment of changes in community advisory board conduct and roles over a five year period found that at each site a conflict or challenge arose in which the views and assistance of community advisory board members became not only valuable to the research team but also important for the future success of the research. These conflicts or challenges generated substantial interactions of mutual benefit as issues were debated which led to a more genuine partnership. Community advisory boards clearly can be dynamic entities striving to better represent and advocate for the communities.


Djomand G, Metch B, Zorrilla CD, Donastorg Y, Casapia M, Villafana T, Pape J, Figueroa P, Hansen M, Buchbinder S, Beyrer C; for the 903 Protocol Team. The HVTN Protocol 903 Vaccine Preparedness Study: Lessons Learned in Preparation for HIV Vaccine Efficacy Trials. J Acquir Immune Defic Syndr. 2008;48(1):82-9 2008

Successful recruitment and retention of HIV-uninfected at-risk participants are essential for HIV vaccine efficacy trials. A multicountry vaccine preparedness study was started in 2003 to assess enrolment and retention of HIV-negative high-risk participants, and to assess their willingness to participate in future vaccine efficacy trials. HIV-negative high-risk adults were recruited in the Caribbean, in Southern Africa, and in Latin America, and were followed for 1 year. Participants included men who have sex with men, heterosexual men and women, and female sex workers. History of sexually transmitted infections and sexual risk behaviours were recorded with HIV testing at 0, 6, and 12 months, and willingness to participate in future vaccine trials was recorded at 0 and 12 months. Recruitment, retention, and willingness to participate in future trials were excellent at 3 of the 6 sites, with consistent declines in risk behaviours across cohorts over time. Although not powered to measure seroincidence, HIV seroincidence rates per 100 person-years (95% confidence interval [CI]) were as follows: 2.3 (95% CI: 0.3 to 8.2) in Botswana, 0.5 (95% CI: 0 to 2.9) in the Dominican Republic, and 3.1 (95% CI: 1.1 to 6.8 ) in Peru. The HIV Vaccine Trials Network 903 study helped to develop clinical trial site capacity, with a focus on recruitment and retention of high-risk women in the Americas, and improved network and site expertise about large-scale HIV vaccine efficacy trials.

Editors´note: Finding populations with sufficient risk for HIV infection to support the seroincidence demands of trials is a start but they must also have high rates of retention for there to be adequate power to confirm or refute the study’s hypothesis. Even participating in a study to assess enrolment, retention, and HIV incidence can lead to declines in risk behaviour and HIV incidence, above those already happening in the overall general population. Such a positive effect of being studied is sometimes called the Hawthorne Effect.


Hughes S, L Cuffe R, Lieftucht A, Garrett Nichols W. Informing the selection of futility stopping thresholds: case study from a late-phase clinical trial. Pharm Stat. 2008 Mar 27 [Epub ahead of print]

In an environment where (i) potential risks to subjects participating in clinical studies need to be managed carefully, (ii) trial costs are increasing, and (iii) there are limited research resources available, it is necessary to prioritize research projects and sometimes re-prioritize if early indications suggest that a trial has low probability of success. Futility designs allow this reprioritization to take place. This paper reviews a number of possible futility methods available and presents a case study from a late-phase study of an HIV therapeutic, which utilized conditional power-based stopping thresholds. The two most challenging aspects of incorporating a futility interim analysis into a trial design are the selection of optimal stopping thresholds and the timing of the analysis, both of which require the balancing of various risks. The paper outlines a number of graphical aids that proved useful in explaining the statistical risks involved to the study team. Further, the paper outlines a decision analysis undertaken which combined expectations of drug performance with conditional power calculations in order to produce probabilities of different interim and final outcomes, and which ultimately led to the selection of the final stopping thresholds.

Editors´note: Early indications that a trial has low probability of success - with success defined as confirming or refuting the trial hypothesis - can lead to the stopping of a trial for futility. Although this saves resources, stopping a trial prior to its conclusion because its key endpoints will not be met makes it impossible to determine whether results for secondary endpoints would have generated useful hypotheses for future investigation. It is important to decide up front what the stopping rules will be with respect to all endpoints and understand the consequences and anticipate them.

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