In my last week at the Infectious Diseases Institute (IDI), I’m looking back over the last three months that I’ve spent here working on the Research strategic plan, while also looking forward to returning home to my project management role with a fresh perspective. I have learned so much during my fellowship about global health issues, treatment of HIV and how to make the most of constrained resources, and I hope to put this new knowledge into practice once I’m back in the US. Continue reading »
Category: Janet’s posts
During her August 2-3 visit to Uganda, US Secretary of State Hillary Rodham Clinton called attention to a new survey that shows HIV prevalence in Uganda has increased to 7.3% in 2012 from 6.7% in 2011 and 6.4% in 2005. The survey suggests that behavior is largely driving the increase. While the Infectious Diseases Institute (IDI) focuses on biomedical prevention and treatment of HIV, psychosocial factors are recognized as critically important to the success of biomedical approaches and IDI employs a large team of experienced counselors to work with clients. One of the issues the counselors frequently report to be driving behavior is the stigma associated with HIV.
The Oxford English Dictionary defines stigma as 1) a mark of disgrace associated with a particular circumstance, quality, or person or 2) a visible sign or characteristic of a disease.
Unfortunately there is still a stigma in the first sense associated with HIV infection, even though many people become infected through no fault of their own. There are not only serious medical implications of the disease, but there can be devastating social consequences when others learn that a person is HIV positive – domestic violence, break-up of families and loss of employment. It’s not surprising that many HIV positive people choose to keep their sero-status a secret, and don’t disclose it even to close family; but it’s tough to live with HIV without the support of family and friends.
For people living with HIV there are also a number of telltale visible signs of the disease, stigma in the second sense of the word, that can be difficult to hide. Kaposi’s sarcoma is the most common cancer in sub-Saharan Africa and occurs even more frequently in immune-suppressed people; this cancer produces visible lesions on the skin and face. Some anti-retroviral drugs can produce a distressing side-effect called lipodystrophy that redistributes body fat away from the face and limbs to the torso.
HIV patients must take their antiretroviral drugs regularly, twice a day, and for some it’s hard to hide this routine from their employers, as well as to take time off work to attend periodic clinic visits. The virus can be transmitted via breast milk. HIV positive mothers are advised either to formula-feed their babies or, if either mother or baby is taking anti-retrovirals, to exclusively breast feed for at least 6 months to minimize the risk of HIV transmission to the baby. As a result, any mother choosing to formula-feed is instantly suspected by others of being HIV positive.
What can be done to overcome the stigma of HIV? Of course, prevention of transmission is vitally important, but for those people already infected, encouragement and peer support can help them focus on adhering to treatment and living long, healthy and productive lives.
Personalized medicine is a hot topic worldwide, offering the promise of tailoring drugs to match the genetic variability of diseases, for maximum efficacy.
As a Center of Excellence for HIV treatment, the Infectious Diseases Institute (IDI) is entering the realm of pharmacogenomics, in seeking to find optimal antiretroviral drug regimens for patients who have developed viral resistance to standard first or second line therapy.
The Human Immunodeficiency Virus replicates very rapidly when it is not held in check by antiretroviral drugs, and genetic mutations can quickly emerge that confer resistance to the drugs to which the virus has been exposed. HIV patients receive combination therapy, a mixture of three different classes of drugs that work by different biological pathways, to keep the virus at bay. One of the main reasons why viral resistance occurs is that patients forget to take their antiviral drugs on time or miss treatment for a period of time. A drop in the drug concentration in the patient’s system for only an hour or two can be enough to allow the virus to break through.
Viral resistance testing is relatively expensive at $120 per test, compared with Uganda’s annual average healthcare spending per head of $106, and so at IDI it is reserved for cases where patients have a consistently detectable viral load (particularly if they are taking second-line antiretroviral treatment), which means the HIV is replicating fast and the drugs they are currently taking have little effect. By sequencing viral RNA taken from the patient, doctors at IDI can see which viral genes have mutated, and check with published literature which drugs will be rendered ineffective by the particular mutations. The doctors can then select a new combination of drugs in the various classes that still have activity against the mutated virus.
Mortality in unchecked HIV infection is high – 30% of HIV patients with virologic failure and weak immunity die within one year – so the new pharmacogenomics technology and personalized medicine approach for treating resistant strains of HIV have potential to save lives.
Last week I traveled to the district of Kibaale in Bunyoro-Kitara, western Uganda, to assess the readiness of some of the Infectious Diseases Institute (IDI)’s Outreach sites for participating in clinical trials. Now that I’ve outlined IDI’s strategic plan for research it’s time to start working out the detail of how to put the high level plans into practice. Continue reading »
I returned from a week of travel yesterday to news of an outbreak of the deadly Ebola virus in Uganda that has claimed 14 lives in a village in Kibaale district, which is 140 miles or about 3 hours’ drive from Kampala. The situation in Kampala is tense, since one of the victims, a health care worker from the district, was transferred to Mulago Hospital, the national referral hospital in Kampala across the street from the Infectious Diseases Institute (IDI) where she subsequently died. Her sister was also admitted to Mulago hospital, where she is stable.
IDI has an Outreach program and several ongoing projects in Kibaale district and it happens that my visit last week was to Kibaale, to assess the readiness of some of IDI’s Outreach sites for participating in clinical trials. At the time I was there we heard about an unknown infectious disease in the area that did not respond to antibiotics and that had claimed several lives, and local health workers were worried. The district was waiting for results from samples tested at the Uganda Virus Research Institute to identify the disease. Little did we know that it was Ebola virus.
IDI has taken immediate steps to provide relief and urgent protection of health workers in Kibaale with donation exceeding $7,500 in medical supplies, protective clothing and food. Due to intermittent power supply, it is hard to refrigerate food so locals usually buy fresh food daily in the markets; however public gatherings including markets have been banned in the region to prevent spread of disease and food supplies are running low. IDI took on a similar role in a previous Ebola outbreak in 2007 by providing protective gear to Mulago Hospital and assistance in setting up an isolation ward.
I visited Kagadi District Hospital and toured the newly refurbished operating theater and laboratory, which are well equipped and staffed but suffer from frequent power outages. Most of the roads in the district are murram, or a dirt road, which makes traveling slow, and for most local people bicycle or walking are the only forms of transport. For many villagers it can take one hour or more to reach the nearest health center. One of the projects being implemented by IDI is the Saving Mothers Giving Life Project. This is a US funded inter agency project supporting several implementing partners in Uganda and Zambia to reduce maternal and new born deaths by 50% within I year in Kibaale, where Kagadi District Hospital is located. Under this project a new ambulance service has recently been introduced which has greatly improved speed of access to emergency care, mainly for mothers with complications in childbirth. The ambulance drivers we spoke with were very anxious about the Ebola outbreak, since as first responders they are vulnerable to exposure.
The Ugandan Ministry of Health, World Health organization (WHO) and US Centers for Disease Control (CDC) all have expert teams on the ground in Kibaale and have issued guidance on how to avoid transmission of Ebola and what symptoms to watch for; Ebola is deadly and there is no cure or vaccine. Rest assured, I feel fine and am very unlikely to be exposed; I always carry hand sanitizer with me. At IDI security checks and hand washing stations have been set up at the building entrances to minimize any risk of infection. Hopefully the initial outbreak has been contained and no more lives will be lost.
How do we categorize different kinds of research – and why?
In new drug development we categorize research by stage: Preclinical, Phase 1, Phase 2 and Phase 3 clinical trials. The research question that we ask at every stage is different: does the drug work in a disease model, is it safe in humans, does it work in human disease, and does it have clinically meaningful benefit?
At the Infectious Diseases Institute (IDI), the purpose of research is to provide evidence that informs health care policy1 and optimizes treatment of disease. I’ve developed a framework for categorizing types of research that’s relevant to the questions IDI asks in seeking to understand and treat disease and to implement its recommendations both in Uganda and via the World Health Organization.
When little is known about a disease, cross sectional surveys can help understand the epidemiology, or incidence and type of disease. An observational cohort study where patients are closely monitored over time while receiving standard of care treatment can help researchers identify areas of unmet need.
Classical randomized controlled clinical trials fit in this category, where a new treatment is compared with standard of care treatment in a carefully selected patient population to see if the new treatment is superior.
It’s not enough for IDI to prove that a new treatment works; the next step is to demonstrate that it can be translated into real life, and show that the treatment works as well in a rural health center as it does at a center of excellence like IDI. Implementation or Operational research is used to demonstrate that a new health care policy can be scaled up nationally.
In a resource-limited setting it’s vital that new treatments are shown to improve not only the benefit to patients but also to lower the cost, to maximize the overall health care bang for the buck. Cost effectiveness or pharmacoeconomic research helps to justify spending money on newer treatments that provide superior benefit to patients.
- “Is Evidence-Based Government Possible?” Philip Davies, 2004
- WHO Alliance for Health Policy and Systems Research: Implementation Research Platform
- “Evidence from Cost-Effectiveness Research” Noyes and Holloway, NeuroRx Vol 1 (3), July 2004
A typical day starts before dawn; soon after the sun is up I’m on my way walking to work, which takes 20-25 minutes depending if I walk at an American or African pace. I pass many of the same people commuting on foot each day; I’m the only Muzungu (white person) so many recognize and greet me.
IDI has regular weekday meetings for research and clinical staff from 8-9am, the hour before the clinic opens, and I often attend these as they are very educational in learning the intricacies and social considerations of treating HIV.
In the mornings I focus on strategic analysis. I’ve been working on two major items: first, data-mining the www.clinicaltrials.gov database to understand what kind of research is going on globally and in Africa in the disease areas of interest to IDI; and second, benchmarking IDI with other sub-Saharan African Research Centers of Excellence.
Once I have gathered and analyzed all the data, I then think long and hard about the patterns I see emerging and the implications for IDI; I’ve developed a number of novel frameworks describing research in this setting that I’ve described in previous blog posts.
I’ve been supplementing the data from IDI internal documents and internet research with 1:1 interviews with IDI researchers, faculty and researchers from Makerere University and external experts working in clinical research in sub-Saharan Africa, both to seek input and confirm or clarify the hypotheses and frameworks I’m developing; so most days I’ll have either a face to face or a telephone interview.
I also meet regularly with IDI’s Research Management to provide an update on the progress I’m making, to share new ideas and to seek their feedback on the new five year strategic plan that I am helping to develop. I’m mentoring several of the mid-level managers and working with them to develop new processes and tools for managing research activities.
The lunch hour is from 1-2pm and I enjoy taking a break and walking to the IDI cafeteria through the clinic waiting room past the craft stall, where I often stop to buy something to support the friends (clinic clients) – I have a huge bead collection by now with a string to match every outfit. Lunch is the same every day – baked beans with rice, posho (maize grits), matooke (steamed plantain) and vegetables – delicious!
In the afternoon I write up notes from my meetings, and reports summarizing my findings, and then at the end of the day I go “footing” home.
As the Infectious Diseases Institute (IDI) starts a new fiscal year, all eyes are fixed anxiously on the budget. IDI is a Center of Excellence, leading the way in defining HIV patient care and treatment through its research activities; but excellence has a certain cost, and IDI’s strategic plan must spell out how that cost will be sustainably met.
The situation is similar for HIV care and treatment in Uganda as a whole; the good news is that national guidelines have been established and anti retroviral drugs (ARVs) are provided free of charge to eligible patients. However ARVs are largely funded by foreign aid, for example the US President’s Emergency Fund for AIDS Relief (PEPFAR) and there are concerns that this is not sustainable and that a mix of government funding and patient copays will be needed longer term to sustain excellent HIV care.
Research excellence requires a certain infrastructure – quality, regulatory, project and grant management. In both universities and research institutes the cost of this infrastructure is typically supported partly by unrestricted government and foundation funding and partly by allowance for overheads in project grants.
A certain portion of IDI’s core research infrastructure costs can be recovered through charging partial overhead and staff costs to grants, but the remainder must be met through revenue-generating activities. How can IDI best balance focusing internally driven research in the areas that matter most, while maintaining the highest quality of research data, and generate sufficient revenue to maintain its core? Any research based organization juggles similar issues – the challenges of meeting quality, cost and productivity goals within the available research budget.
As IDI approaches its tenth anniversary, it will enter a new era as a self-sustaining research institute at a time of austerity in the global funding environment. The changes in IDI’s external environment necessitate a paradigm shift in the way that IDI does business in the future. While there will continue to be opportunities for efficiencies that will bring about incremental cost savings, these may alone not be enough to cover the core costs of maintaining a center of excellence. Filling the gap will require innovation, which is what IDI does best. By focusing on key research areas and emerging market opportunities, and by having flexible staff that can multitask across projects, IDI can sustain excellence for years to come.
Do you remember the 2000 movie ‘What Women Want” in which an advertising executive played by Mel Gibson develops the ability to read women’s thoughts after an electric shock in the bathtub?
I haven’t been struck by a lightning bolt, but I have developed some insight into what motivates clinical researchers in Uganda, both within the Infectious Diseases Institute (IDI), and at Mulago Hospital nearby, from one-on-one conversations we’ve had while thunder rumbled overhead and rain pelted down on the roof from the late rainy season storms. Researchers here have an unquenchable thirst for knowledge, something that is often taken for granted in the US and Europe.
● On a personal level many of my colleagues at IDI are pursuing higher degrees, whether PhDs or Masters programmes, in order to learn new capabilities to better their careers.
● On a clinical level, researchers are curious to understand the reasons behind conundrums they observe in medical practice. In the recent past, before rapid diagnostics tests were available, national guidelines required any patient (particularly children) presenting with a fever to be treated for malaria; and before CD4 testing – measurement of the white blood cells called T helper cells that protect the body from infections via the immune response – was available in rural areas, patients would be started on antiretroviral treatment based on clinical symptoms alone. It’s thanks to researchers in centers of excellence like IDI that today evidence-based point-of-care solutions are available to better guide treatment.
● On a public health level, very little is known about the epidemiology of a number of serious diseases in Africa. Hepatitis B prevalence exceeds 20% in some areas but screening, prevention and treatment are virtually non-existent. Cervical cancer and Burkitt’s Lymphoma are major killers but have been little studied here, and there are unexplained clusters of breast cancer in young women with no family history of the disease.
There are so many unanswered questions and so much research to do here! Knowledge is power – the power to treat disease. An important element of the research strategy that I am developing is how to attract, build and retain top scientific talent, by ensuring that IDI understands what motivates researchers and provides opportunities for knowledge creation. I hope that I can help IDI prioritize and drive its research agenda, and attract the funding to address these areas of unmet need.
This week I’ve been benchmarking Centers of Excellence for Research in HIV in Uganda and other African countries to understand the different business models and critical success factors for conducting clinical research. All these centers share a common tripartite mission of patient care, research and training in HIV / AIDS.
“No man is an island” said English poet, John Donne, and this is very true in clinical research. Clinical trials in both the US and in Africa can only succeed through organizations working together in multiple partnerships.
1) International founding partners
Most Research Institutes in Africa were first established in broad partnership with a US or European research organization; the Infectious Diseases Institute (IDI) with Pfizer, Uganda Vaccines Research Institute (UVRI) with UK Medical Research Council (MRC), the Makerere University-Johns Hopkins University Research Collaboration (MU-JHU) focusing on reducing mother to child transmission of HIV with Johns Hopkins, and Center for the Program of AIDS Research in South Africa (CAPRISA) with Columbia University. Such partnerships enable academic exchange and access to research funding from NIH and other international sources.
2) Partners for patient access and care
While African Research Institutes have established their own specialist and rural clinics to provide patient care and have created patient cohorts for research studies, they also partner with national and regional hospitals like Mulago adjacent to IDI, and Gulu in Northern Uganda to recruit additional patients for clinical trials and to provide inpatient care if needed. Several centers that pioneered African trials of HIV antiretroviral drugs including CAPRISA and the Joint Clinical Research Center (JCRC) are members of the AIDS Clinical Trial Group and participate in international multi-center trial networks.
3) Partners for clinical and lab data management
IDI and other Research Institutes have established internal capabilities to support clinical trials including laboratories for diagnostic and clinical biomarker testing, and data management units. However some specialized tests are outsourced to partner laboratories, either in Africa or internationally; and technology can enable remote data management by local or international partners.
4) Partners for Policy Change
The ultimate goal of clinical research in Africa is to establish national health policies that are based on scientific evidence. Effective partnership with the Ministry of Health in planning studies, disseminating the results and effecting and implementing heath policy changes is key.
IDI will need to extend and strengthen partnerships in these four key areas to ensure continuing success in the future.