When the band stops….

If you don’t normally read my Early Career columns you should know two things about me to understand the context of this piece:  1) I am a nurse and 2) My day job is as a researcher examining how to improve heart health in adults living with HIV.

The first time I heard of HIV was when my middle school health teacher played the movie “And the Band Played On”. If you haven’t seen the film or read the book, it’s the story of early years of the HIV crisis in America. Yes, it’s about the intersection on politics and health in the face of an unknown virus spreading among marginalized and vulnerable people. But it’s also about how scientists, health care professionals, advocates, and people from all walks of life come together to create a groundswell of tangible support and change for those infected with and affected by HIV.

I’ve been thinking a lot about this film these days in the midst of the COVID-19 pandemic. When every day I wake up wondering what the headlines will be and every song on the radio, speech, and swing of the stock market seems fraught with apocalyptic symbolism. There is a pervasive, and understandable, fear of the unknown, desire for control, and for some an insidious need to blame others for disease.  And then there is the grief. The grief not only for those who have and will succumb to this virus. But the widely felt grief that life will never be the same as it was before COVID-19 came into our consciousness.  It reminds me of how patients and caregivers have described the early years of the HIV epidemic.

But in the 40 years since the HIV epidemic what have we learned that can help us today? I’d also love to hear your thoughts on this but here those I’ve been thinking about.

  • Trust science. It’s a very human instinct to believe in quick cures and conspiracy theories but the only thing that will help us understand how to prevent, mitigate, and treat COVID-19 is science. Science is a careful, systematic, data-driven and rigorous process by which hypotheses are developed, tested, refined and re-tested until we have the answer. This is how we developed the first HIV tests and highly effective HIV medications, and it is also how we are slowly inching forward towards an HIV vaccine. This is how we are now developing a test for COVID-19, how we will develop treatments, and eventually how we will develop a vaccine. Do your best to ignore any advice, product, or theory you hear that is not grounded in the scientific method and widely shared by reputable scientists.
  • Be kind. People are going to say and do things you don’t agree with a lot over the next few months. People are going to be stressed out with new family, work, financial and social pressures. We are undoubtedly going to be asked to give more up than we have had to give in maybe a generation. Some of us are going to have to work more hours than we thought possible (at least since work hour restrictions were enacted). So, while it’s going to be hard, we need to take extra care to be kind to one another—to say kind things; restrict the sarcasm, judgment and unsolicited advice (in person and on social media); drive a little more calmly; and simply find ways to share kindness to your family, community, team, and neighbors at a responsible distance.
  • The band is more than the conductor. To get through this pandemic, we will need to draw on the skill sets of many. We need those skilled laborers who work to manufacture personal protective equipment, delivery teams who make sure the equipment gets where it needs to go, we need people to sanitize and stock grocery stores, we need musicians and artists to remind us to see the beauty in the world around us, and telecommunications staff to make sure the internet works. And in health care settings—the epicenter of the pandemic—we need food service workers, respiratory therapists, housekeeping staff, administrators, pharmacists, social workers, schedulers, faith leaders, nurses, advanced practice professionals, and physicians.  They are part of a health care machine that will keep us safe and ensure that many of us never see the worst of this disease. Few chose these jobs anticipating high salaries, professional autonomy, or glory, and many will not be publically acclaimed as heroes for their critical contribution during this time. But like all front line soldiers, they deserve our respect, honesty, protection and acknowledgment; and we must encourage those who are leading during this time to recognize this valuable work.

The title “And The Band Plays On” refers to a society that by and large ignored the early AIDS epidemic which led to increased transmission of HIV and countless deaths. Despite some similarly notable fumbles by political leaders, the COVID-19 epidemic is not the early HIV/AIDS epidemic. In the span of less than a week, hundreds of millions of people in the United States and around the globe have listened, learned, and stopped in an effort to decrease transmission and reduce deaths. We don’t yet know if these actions will work, and we may never fully understand their impact.  That we collectively acted (or in this case stopped acting) tells me that we will weather the next few months as long as we do so together.

“The views, opinions and positions expressed within this blog are those of the author(s) alone and do not represent those of the American Heart Association. The accuracy, completeness and validity of any statements made within this article are not guaranteed. We accept no liability for any errors, omissions or representations. The copyright of this content belongs to the author and any liability with regards to infringement of intellectual property rights remains with them. The Early Career Voice blog is not intended to provide medical advice or treatment. Only your healthcare provider can provide that. The American Heart Association recommends that you consult your healthcare provider regarding your personal health matters. If you think you are having a heart attack, stroke or another emergency, please call 911 immediately.”




Paradigms and Progress in HIV and Cardiovascular Health

 “Led by a new paradigm, scientists adopt new instruments and look in new places” – Thomas S. Kuhn

For a lot of rational (and some irrational) reasons, hearing the word HIV evokes fear, anger, and sadness. When I first heard about HIV, I was an elementary school student in late 1980’s and at that time, HIV was almost always a death sentence.  But today that is not the case.  Today, due to the hard work of scientists, patients, volunteers, advocates, and countless others, HIV is a chronic, manageable disease. An accomplishment epitomized by the oldest known person living with HIV recently turning 100 years old.

living with HIV graph

While this progress and longevity should be celebrated, the flip-side of age is that it is the primary driver of cardiovascular disease (CVD). In fact, this longevity has ushered in a new era where adults living with HIV are at exceptionally high risk of cardiovascular diseases including heart attacks, heart failure, and stroke. A recent meta-analysis by Anoop Shah, MD, from the University of Edinburgh, found that the global burden of HIV-associated cardiovascular disease has tripled in the past 20 years, especially in low and middle-income countries. Now, after more than two decades of accumulating evidence in this field, the American Heart Association released earlier this month a Scientific Statement on the characteristics, prevention and management of cardiovascular disease in people living with HIV.

Directed at all who support adults living with HIV, this statement is a general roadmap for raising awareness about the increasing burden of CVD in this population. However, it offers few new tools for providers to use, due primarily to the lack of high-quality “clinical trial data on how to prevent and treat cardiovascular diseases in people living [and aging] with HIV investigating cardiovascular endpoints” said Matthew J. Feinstein, M.D., M.Sc., chair of the writing group for the statement and assistant professor of medicine at the Feinberg School of Medicine, Northwestern University.

Still, what the existing (mostly observational) evidence allowed the writing group to do was to develop a pragmatic approach to assessing and preventing cardiovascular disease in treated HIV (Figure above). This approach includes the following:

  • Ensure all patients living with HIV are on effective HIV treatment
  • Determine risk of cardiovascular disease using tools such as ACC/AHA 10-year ASCVD risk estimator and a family history
  • Optimize lifestyle approach to prevention (e.g., smoking cessation, physical activity, healthy diet intake)
  • If at high risk and between the ages of 40-75 years, talk with the patient about the risks and benefits of lipid-lowering therapy while exercising caution for drug-drug interactions

Yet, while the new AHA Scientific Statement will be an important catalyst for the field, in many ways it creates more questions than answers. For example, are we shifting to a new paradigm in HIV care? Do we need new tools to help reduce CVD in this population or are the general recommendations for risk stratification and lifestyle optimization sufficient?  What is the most effective way to get either existing or new clinical tools to the high-risk patients living with HIV?

Fortunately, some of these questions are starting to be answered. The REPRIEVE study is the first large scale (>8,000 people) clinical trial to test if a daily statin reduces cardiovascular disease in adults living with HIV. Results are expected in the next 3-4 years. Additionally, the PRECluDe grants at the National Heart, Lung, and Blood Institute have stimulated new implementation science research focused on understanding how to best adapt effective CVD prevention studies to the real-world settings where people living with HIV receive their health care. These initiatives, coupled with ongoing research on the discovery of mechanisms of CVD and the testing of CVD prevention interventions in people living with HIV, will eventually allow for the development of guidelines on the prevention and management of CVD in HIV—the true instrument needed to help improve cardiovascular health for all adults living with HIV.



A Tale of Two Heart Attacks

Differentiation between Type 1 and Type 2 heart attack according to the condition of the coronary arteries (Thygesen, et al., 2012, Circulation)

Differentiation between Type 1 and Type 2 heart attack according to the condition of the coronary arteries (Thygesen, et al., 2012, Circulation)

Crushing. Stabbing. Gut-wrenching, knock the wind right out of you sort of pain in your chest, arms, neck, jaw or back.  This is how we commonly think of heart attacks and for patients and their loved ones – it is the worst of times. But just before the pain or discomfort starts, your body is adjusting to the cause of the heart attack and those causes can be classified as either Type 1 or Type 2 heart attacks. There are actually 6 types of heart attacks, but the vast majority of heart attacks, including those experienced by people living with HIV, are either Type 1 or Type 2.

A Type 1 heart attack is when a person has a sudden block in their blood flow, usually related to a blood clot that has broken off from a plaque, resulting in reduced oxygen going to the heart and death of heart muscle cells.  Whereas a Type 2 heart attack is when the heart needs more oxygen than it gets, due a number of potential causes including a spasm of the heart vessels, critical illness (including sepsis, very low blood pressure, and respiratory failure), or those undergoing surgery.

As I’ve previously written, HIV doubles the risk of heart disease and doubles the risk of having a heart attack. But in order to understand how to reduce this risk, we need to better understand what causes heart attacks in people living with HIV.  Building on previous work demonstrating that half of the heart attacks in people living with HIV are Type 2 heart attacks, Crane and colleagues recently presented new research on the differences in types of heart attacks among people aging with HIV. In over 27,000 adults living with HIV, the investigators determined the type of heart attack, probable cause of all Type 2 heart attacks, and looked at the rates of heart attack by age.

causes of type 2 myocardial infarction among people living with HIVThey identified over 1,000 Type 1 and 2 heart attacks and found that age was a primary predictor of the incidence and type of heart attack. Younger people with HIV had 10-fold more Type 2 than Type 1 heart attacks (although rates were low – only 22 heart attacks in this age group).  Starting in their 50’s, people living with HIV experienced significantly more Type 1 heart attacks than Type 2. Most interestingly were the heterogeneous causes of the Type 2 heart attacks including sepsis, respiratory failure, pneumonia, hypertensive emergency, and GI bleeds (Figure 1).

When asked what initially prompted this work, Dr. Heidi Crane from the University of Washington Center for AIDS Research states, “As an awareness of the importance of Type 2 heart attacks has grown in the general population, we were struck that there was so little data in people living with HIV- a population which has twice the rate of heart attacks as the general population.” This new study demonstrates that younger adults living with HIV are more likely to have Type 2 heart attacks from heterogeneous causes, which change the prevention strategies needed for this group.  While prevention strategies for Type 1 and 2 heart attacks require attention to traditional risk factors, we also need to pay attention to other non-traditional causes that may put someone with HIV at risk for heart attack due to supply-demand mismatch. Ultimately, these prevention strategies will need to be as heterogeneous as the causes. Dr. Crane continues, “There’s not going to be an easy fix for Type 2 heart attacks, there’s a lot going on and we will need to dive deeper to understand how to best tailor strategies to the individual patient.”

And yet, we’re often told that we need to treat the patient, not the disease. But in order to treat the patient, we have to know them, listen to them and understand the risk factors that they face as individuals for heart attacks. Whether it is a chronic disease like HIV infection or some other inflammatory condition, we will need to avoid the temptation to apply blunt prevention strategies, and favor the more challenging personalized solutions.

What are your experiences diagnosing and treating Type 2 Heart Attacks? How can we do a better job preventing them in people living with HIV and others at high risk? Tweet at me at @AllisonWebelPhD to follow the conversation.


Thumbnail photo credit: Photo by Kelly Sikkema on Unsplash

Thumbnail photo credit: Photo by Kelly Sikkema on Unsplash






Red Dresses & Red Ribbons: What Every Health Care Provider Needs to Know about Cardiovascular Disease and HIV in Women

Lead Image (created by Cynthia Rentrope):

Lead Image (created by Cynthia Rentrope):

Each February, we celebrate Go Red for Women – a time for healthcare providers to reacquaint ourselves with the shocking fact that on average one woman dies from cardiovascular disease (CVD) every minute – and recommit to doing better. In the United States and the around the globe, women living with HIV are at higher risk for developing cardiovascular disease, yet not all women are affected equally. There are disparities in the quality of cardiovascular care in women, especially younger women, compared to men. Simultaneously, women living with HIV are at increased risk for cardiovascular disease than HIV uninfected women and receive less guideline-based cardiovascular care. In order to provide better preventative, diagnostic, and curative care we have to understand why women living with HIV are at higher risk for cardiovascular disease and stroke and what we can do about it.

Women living with HIV are at higher risk for CVD and stroke

The reasons why women living with HIV are at higher risk for CVD and stroke are not entirely understood. However, scientists have described several likely reasons. HIV is an inflammatory disease and women infected with HIV have higher levels of inflammatory cytokines and markers of immune activation. In turn, this inflammation may increase the risk of CVD by accelerating development of atherosclerotic plaques and making these plaques more ‘vulnerable’ to rupture, causing more heart attacks and strokes. Additionally, we recently reported that inflammation was also associated with reduced cardiorespiratory fitness in adults living with HIV, which may help explain this increased risk. Women living with HIV have elevated rates of depression, obesity, stigma, and homelessness, also associated with increased CVD.

However, there are also unique biological factors that increase the risk for CVD in women living with HIV, particularly with aging. According to Dr. Sara Looby RN, PhD, Assistant Professor of Medicine at Harvard Medical School and Massachusetts General Hospital, hormone changes experienced during menopause such as estrogen loss and reduced ovarian reserve may negatively influence immune activation and the development of subclinical CVD in women living with HIV.  Her current study funded by the National Institute of Allergy and Infectious Disease is exploring this and the results are expected in the next 4 years.

Strategies to Reduce the risk of CVD in Women Living with HIV

Yet it is not enough to know there is a risk and even to partially understand why; health care providers- cardiologists, nurses, primary care providers, and HIV and emergency room physicians -chose their profession because they wanted to improve health. And all of us have an important role in helping women living with HIV accomplish this goal. There are several evidence-based strategies we can use to improve cardiovascular health in this population.

  • Take HIV medications. This strategy is well known among HIV nurses and physicians but those not trained in HIV may not realize the significance of HIV medications to reducing CVD in this population. Having a suppressed HIV viral load, obtained through adherence to effective HIV medicines, is consistently associated with reduced CVD.
  • Recognize and treat the cluster of traditional cardiovascular risk factors in HIV. Increased traditional cardiovascular risk factors in women living with HIV, including hypertension, dyslipidemia, diabetes, and obesity, need to be effectively addressed using guideline-based care. For a good resource on how to do this, check out the American Heart Association’s Life Simple 7
  • Assess sex-specific risk factors in women including menopause history. This may not be routine for HIV, cardiovascular or family health providers but it is important for understanding cardiovascular risk. Increasing evidence indicates we should use a woman’s menopause history to improve understanding of her risk of CVD and provide good cardiovascular treatment. Other health conditions unique to women, such as a history of pre-eclampsia, can also influence risk and are recommended as “risk enhancers” in the most recent AHA Cholesterol Practice Guidelines.
  • Engage women in their cardiovascular health. While this may be the hardest strategy to implement, it is the most important because for so long, women living with HIV have focused on surviving HIV that they do not perceive they are at elevated CVD risk. Dr. Looby acknowledges, “It can be difficult to find time to do this given the competing demands of clinical care, but education is essential to empowering women living with HIV to become active participants in their care. Delivering education in plain language that is easily understood by patients. Asking patients basic questions like, “Do you know what heart disease is?” or “Do you know your cholesterol levels and what they mean?” can provide simple snap shots of important information that can be built upon at subsequent visits, or followed up by providing supplemental educational materials.” Through this patient-focused engagement women living with HIV will be able to take charge and reduce their blood pressure, cholesterol, weight, and smoking resulting in improved cardiovascular health.

Almost every minute a woman dies from heart disease. But they don’t have to. We are privileged to serve in a profession dedicated to improving the health of our fellow humans. But human health is complex and, for women living with HIV, we cannot just treat their HIV or their CVD or their depression or their symptoms of menopause- we have to treat these intertwining conditions together. There are countless barriers to doing this well, and as new models of delivering cardiovascular care in HIV are under investigation, I am confident we will learn how to do this better. In the meantime, we have start today and commit to implementing strategies in our own practice to improve the heart health of women living with HIV.



A New Year, A New Story: Tips for a Healthy Lifestyle in 2019

A new year presents a new opportunity for improvement. Each year, thousands of advertisements beckon us to join or buy the most recent fitness and wellness craze – wearable technologies, personal coaching, pea protein and oat milk. However, if trends are not your thing, you may find it reassuring that “traditional” fitness and wellness strategies (e.g., training for a 5K walk/run, taking the stairs instead of the elevator, and reducing your sugar intake) can also be re-imagined and integrated into your daily routine leading to a healthier, and likely happier you.

Perhaps contrary to the many images trying to sell wellness products, adopting fitness and wellness strategies are equally if not more important for those who are living with a chronic disease. In November 2018 at the American Heart Association Scientific Sessions, the Physical Activity Guidelines were updated and, for the first time, specified that physical activity can help to manage chronic conditions including decreasing pain, reducing the rate of progression for high blood pressure and diabetes, reducing anxiety and depression, and improving cognition in those with chronic comorbidities. These critical health outcomes symptoms are particularly important for adults living with HIV, who tend to experience worse symptoms than many living with other chronic illnesses – and consequently, they may stand to benefit the most from increased and improved physical activity.

Figure 1 Photo by Christine Schmitt via flickr (http://bit.ly/2LZufoz)

However, in addition to physical activity, nutritional intake is a critical part of improving health and wellness among adults living with HIV. A recent practice paper of the Academy of Nutrition and Dietetics found that nutritional status affects the overall health and longevity of this population. They suggest that improved diet can lead to reduced blood pressure, obesity, and diabetes, which will result in improved cardiovascular health. Lead author of the report, Amanda Willig, RD, PhD, from the University of Alabama at Birmingham, suggests that when anyone (especially someone with a chronic disease such as HIV) is starting to adopt a new diet to “Remember, the enemy of good is perfect. A perfect diet is not needed to see big changes in your health.”

So what are the good diet changes needed to improve health? Regardless of one’s HIV status, Dr. Willig’s recommendations on healthier eating are the same: “Watch your portion sizes, try to eat vegetables every day / fill ½ of your plate with vegetables at meals, limit the amount of sugar in your diet, and choose water over sugar sweetened beverages like soda, sports drinks or sweet tea.”

However, for those with HIV, there are some special considerations. While the evidence is still emerging, Dr. Willig indicated that those with HIV may need more Vitamin D than they did prior to their HIV infection for their overall health.  And if one’s CD4+ T-cell count is less than 250, they may want to avoid eating raw or undercooked meat and seafood, as they be at higher risk for food poisoning. Additionally, for the growing number of people living with HIV who are over 50, they may need to increase their protein intake from 0.8 grams per kg per day to 1.2 grams per kg per day. This will help with maintaining muscle mass and preventing bone loss.

Yet whether you are decreasing your portion size or increasing your daily protein intake, changing behavior can be hard and as we age, it can seem complicated and sometimes discouraging. In addition to seeking help from registered dietitian or a Physician Nutrition Specialist who can help you decide which lifestyle nutrition plan is best suited to you, Dr. Willig also suggested several tips for adopting a healthy diet in 2019 (see insert).


Dr. Willig’s Tips for Adopting a Healthy Diet in 2019

  • Keep a food diary for 3-4 days to learn not just what you are eating but why.
  • Start with the small steps that can produce big changes, such as cutting out sugary drinks or not eating during the night.
  • Regardless of the nutrition plan, portion sizes still matter. One can eat too many of the “right” foods, so learn what a portion of the foods you eat actually looks like.
  • Make sure your nutrition plan fits your lifestyle. If you want to cook, you can to experiment with baking and sautéing instead of frying foods. If you travel often, learn to read nutrition labels and restaurant nutrition information to avoid eating too many calories.


Additional strategies can be found on the American Heart Association’s Healthy Living Website.

As you start to navigate how to start the year committed to becoming healthier you, there will undoubtedly be challenges – busy schedules, competing demands, mood, weather and so on. But you can overcome them and take small steps to become a healthier you in 2019. As you start this journey, consider the words of writer Alex Morritt, “New year — a new chapter, new verse, or just the same old story? Ultimately we write it. The choice is ours.” The new year has just begun, and regardless of your age, sex, health status, or neighborhood in 2019 you get to write your own story – one in which you relentlessly pursue a healthier you.



Heart Health and HIV: An Opportunity for Global Health Partnership

Slightly over five years ago, I immersed myself in a growing literature that documented the increase in heart disease in people living with HIV (PLHIV). While almost of all of these studies were in well-developed “high income” countries, the conclusion was always the same. The HIV medications worked, and those who had access to them were aging and developing conditions associated with aging including, prominently, cardiovascular disease (CVD). People living with HIV seemed to be developing these conditions more frequently than those who were not living with HIV, and no one was able to tease apart the myriad reasons why this was happening.


Global Burden of Atherosclerotic Cardiovascular Disease in People Living With HIV                                          
DOI: (10.1161/CIRCULATIONAHA.117.033369

Others had the same realization and earlier this year. Anoop Shah, MD, from the University of Edinburgh, conducted the first meta-analysis examining the global burden of CVD in PLHIV. Pooling data from almost 800,000 PLHIV with 3.5 million person years of follow up, they found that the global burden of HIV-Associated CVD has tripled in the past 20 years, especially in low and middle-income nations.

Specifically, Dr. Shah and his team measured the population attributable fraction of CVD in PLHIV. This metric combines the risk associated with CVD with the prevalence of HIV- an approach that can quantify the actual impact of risk on a population. This is important because in low and middle-income countries where the HIV prevalence is high and resources are scarce, interventions to reduce the risk of CVD will likely have a bigger impact. Dr. Shah’s work revealed that those in sub-Saharan Africa experience a “double hit” of both HIV and CVD, with higher rates of traditional risk factors such as high blood pressure, and context-specific risk factors including air pollution.

To address these risk factors, Dr. Shah suggests that while there are studies leveraging cutting edge science to help us identify those living with or at risk for CVD (e.g. biomarkers), we need more research testing evidence-based strategies to improve cardiovascular outcomes in PLHIV in low and middle-income countries. This includes testing traditional pharmacological (e.g., antihypertensive and dyslipidemia) and non-pharmacological (e.g., diet, exercise and smoking cessation) strategies tailored to the setting and the population. Critically, this research must also account for the pivotal role health systems have in delivering these interventions.

This year the theme of World AIDS Day is “Building Partnerships through Leadership” and Dr. Shah captured this promise when discussing how to improve health systems to reduce CVD.  “Based on my experience, in Sub-Saharan Africa HIV clinics are incredibly well run and effective, but they only do one thing- treat HIV; but what if we could partner with this HIV clinics across Africa [and other low and middle income settings] to start to provide better CVD prevention and treatment? By building on the existing systems, and expanding to other populations, we could deliver the change that is needed to improve cardiovascular health to PLHIV and beyond”.

Today is World AIDS Day and I am part of the first generation where AIDS has always existed.  I was born a week after the MMRW report  documented the first case of what would become known as AIDS. Since then we have made so much progress, and continue to make strides in preventing, treating, and eventually curing HIV. I look forward to the day when HIV will no longer be a part of anyone’s life. But until that happens, my work, and the work of many scientists, clinicians, advocates and allies will continue to build a better understanding of how to help all PLHIV enjoy the healthiest life possible, with less risk for cardiovascular diseases and stroke.  By working with HIV organizations there are incredible opportunities for innovative and exciting partnerships to improve cardiovascular health in PLHIV, and millions of others around the globe. The American Heart Association can and should have an important role in this quest for longer, healthier lives.

Over the next year, I will explore what is known about the various causes of cardiovascular disease in this population in this series on Heart Health and HIV. I will work to incorporate high quality science with the perspectives of the both clinicians caring for PLHIV and the voices of the patients themselves. I look forward to engaging with all of you and, together, trying to solve these important issues.




Collaborative Studies: Are They Worth It?

In a small evening session at the 51st annual Society for Epidemiologic Research meeting in Baltimore, MD, a group of epidemiologists from Johns Hopkins Bloomberg School of Public Health discussed the how and why of collaborative studies. Dr. Bryan Lau, Dr. Keri Althoff, Dr. Josef Coresh, Dr. Jessie Buckley, and Dr. Lisa Jacobson each presented on a key aspect of conducting successful collaborative studies, from getting investigators on board, to various data methods to address the inherent challenges of such heterogenous data.

Even after a long day of workshops, this session piqued my interest. The discussions – both candid and practical – addressed sides of collaborative science I had never thought of.

Note: This post will be 1 of 3 (or more!) on collaborative studies. Scroll to the end to see other topics I plan to address and leave a comment or Tweet us with feedback or questions.

Not All Collaborative Studies Are the Same

Let’s start with what we’re talking about when we say “collaborative study”. Dr. Lau presented this working definition: a collection of multiple independent studies collaborating together for a scientific goal.

This broad definition groups together many different types of collaborative studies, from multi-site randomized trials with standardized protocols to pooled data from several different cohort studies. What these different examples have in common, however, is at least some overlapping data elements and buy-in from leaders of each participating study. I learned that these two ends of the collaborative science spectrum are often driven by common disease versus common population.

the spectrum of collaborative studies

Common Disease

Studies of the same disease area typically have extensive overlap of data elements that are key in analyzing the condition. Dr. Lau gave the example of HIV, with the North American AIDS Cohort Collaboration of Research and Design (NA-ACCORD), and CD4 count, viral load, and other measures almost always collected in HIV/AIDS research.

How could we apply that to cardiovascular and chronic disease research? It would be nearly unheard of to explore a heart disease question in a data set lacking medical history of diabetes, stroke, MI, hypertension; clinical measures such as total cholesterol, LDL-cholesterol, triglycerides, and troponin in acute care questions.

Common Population

In contrast, if we want to examine childhood predictors of cardiovascular disease, we may combine different cohorts that start following participants at a young age. Unfortunately, these cohorts may be centered around different research questions – environmental exposures, asthma, developmental disorders – and may lack the research elements we want for cardiovascular risk, like basic lipid panels. Alternatively, some cohorts may have half of the data elements we want, but the other cohorts have the other half, and there’s nothing overlapping between them. How would we approach our analyses? We’ll talk about that in my post next month.

For now, let’s wrap up with a summary of the pros and cons of even conducting a collaborative study. With the picture I’ve painted so far, it seems like it can be frustrating, challenging, and perhaps not even doable.

Want to dig in more? Check out this paperCollaborative, pooled and harmonized study designs for epidemiologic research: challenges and opportunitiespublished earlier this year in the International Journal of Epidemiology, by Drs. Catherine Lesko, Lisa Jacobson, Keri Althoff, Alison Abraham, Stephen Gange, Richard Moore, Sharada Modur, and Bryan Lau.

Why Should You Conduct a Collaborative Study?

The two main reasons we often put together collaborative studies is to increase sample size and try to increase generalizability.

Sample Size

Often a collaborative study can address research questions that aren’t answerable in the independent contributing studies – due to a lack of statistical power.

If you’re studying a rare outcome or exposure, or want to conduct subgroup analyses, you need numbers.


With increased sample size, you might think we have a better chance at generalizability. That’s a common misconception too large to address today, but you’re line of thinking isn’t completely wrong. 

By combining different study populations, we’re getting closer to emulating a target population (if that is your target population), and that is why we have the potential for increased generalizability.

Note that I said potential – this segues into our discussion of the cons (or as I like to call them, challenges to overcome) in conducting collaborative studies.

Bigger Not Always Better

Increased sample size does not guarantee generalizability, as I outlined above. Similarly, all of that data coming in from each individual study may be subpar in data quality, and then you can’t combine it for your rare disease analysis or subgroup analyses. What will you do then? (Hint: in the next post on analyses strategies for collaborative studies, we’ll talk about how to optimize your meta data methods).

What else? Like I mentioned before, you may have all of your data elements measured in your contributing studies, but with no overlap. That can lead to unbalanced confounders. Let’s say all of your clinically measured hypertension variables are from two large studies out of the ten you’re combining. Are those two studies representative of the others? A similar issue is overall data harmonization, which can be thought of as a form of complete case analysis. Do you conduct your analyses with the lowest common denominator data elements – those that all studies have in common? We’ll talk more about meta data visualization and individual pooled analyses in the next post.


How do you get buy-in from each study? Can you imagine the egos and the bureaucracy? Dr. Joe Coresh had some great advice from his work with Morgan Grams and the CK-EPID collaboration on how to smooth over logistical issues, from data use agreements, computational infrastructure, and transparency in procedures. Dr Lisa Jacobson had great advice, too – how to involve everyone in analyses, give primary authorship to contributing study investigators, and other tips and tricks for a successful collaboration. We’ll talk about that in post 3 of 3. Looking forward to it – hope you are!

Upcoming Posts:

  • Analytical strategies for harmonizing data in collaborative studies
  • How to conduct a successful collaborative study: the nitty gritty
  • Interested in something else specific? Leave a comment or tweet us @BaileyDeBarmore and @AHAMeetings to let us know!

Follow Drs. Althoff and Lau on Twitter for great EPI methods tweets

Bailey DeBarmore Headshot

Bailey DeBarmore is a cardiovascular epidemiology PhD student at the University of North Carolina at Chapel Hill. Her research focuses on diabetes, stroke, and heart failure. She tweets @BaileyDeBarmore and blogs at baileydebarmore.com. Find her on LinkedIn and Facebook.


When Survival Benefit Transcends Infection Risk

The 22-year-old single mom flags me down at the dialysis unit. “The transplant team discussed getting my consent for increased risk kidney donors – do you think this is something I should go for?” Disclaimer: I’m not a transplant nephrologist. Worrisome thoughts hit my mind… She is so young. Why take on any risk of contracting HIV or hepatitis C? Patients so young will need at least 2-3 transplants through their lifetime. Will she really get a good quality kidney that will hopefully function for 15-20 years, if it was from an increased risk for disease transmission (IRD) donor? (The “increased risk” refers to behaviors that increase risk of contracting HIV, hepatitis B or hepatitis C.)

Fortunately, transplant outcomes data has been reassuring and shows that organs from IRD donors are non-inferior to non-IRD organs. In fact, a recent report from the American Journal of Transplantation showed a survival benefit in accepting IRD kidneys. In patients who declined an IRD kidney, only 31% later received a kidney transplant (5 year follow up period) and this was of a lower quality than the initial IRD organ offered.
Organ transplantation from a deceased donor is the ultimate paradox of a new lease on life from someone other’s tragedy. But the reality is that most patients waiting for a transplant will die before an organ becomes available. There are ~115,000 people on the UNOS (United Network for Organ Sharing) wait list and the majority are waiting for a kidney transplant (~95,000); average wait-time for a kidney from a deceased donor is 5 years. The longer a wait-listed dialysis patient is living with kidney failure and is exposed to the uremic constellation of metabolic derangements, inflammation, anemia and blood pressure fluctuations – the higher the risk of progressive vascular injury and sudden cardiac death. End stage kidney failure is a huge public health burden, totaling $34 billion per year in Medicare spending.

Thus from the perspective of both the individual patient and tax dollars, optimizing the number and quality of transplants is a big deal. Which brings us back to the topic of IRD donors who have a history of behaviors that put them at risk of having HIV, hepatitis B or hepatitis C. Many of these donors are otherwise young and relatively healthy; this means that there is the potential to transplant high quality organs from 1 donor to as many as 8 recipients. In the U.S. we are seeing an alarmingly fast-growing segment of IRD organ donors in the opioid overdose crisis. In 2016 there were ~42,000 deaths from opioid overdose, a five-fold increase from 1999.

A recent NEJM correspondence states “the drug-abuse epidemic has been associated with a sharp increase in the recovery of organs from brain-dead donors in the United States but not in Europe”. In the U.S., the proportion of organ donors who died from drug intoxication increased from 1.2% of all donors in the year 2000 to 13.7% as of 2016. In contrast, the Eurotransplant registry from 8 European countries showed no significant change (≤1% per year). The outcomes data from this donor population is the silver lining in this tragic crisis. In an Annals of Internal Medicine analysis of almost 20,000 organs transplanted from over 7,000 drug-overdose donors, 5-year patient and graft survival was similar as compared to organs from trauma- or medical-death donors.

The majority of IRD donors who have no prior history of HIV or hepatitis won’t have a transmissible virus. But right now we don’t have tests that allow us to be 100% certain about a donor’s infectious status at time of organ procurement. The concept of “increased risk” refers to the risk of recent acquisition of HIV or viral hepatitis that is missed in the Nucleic Acid Testing (NAT) window period. (Window period = the time between potential infection and the point when the test will give an accurate result, thus you get false-negative results.) Don’t get me wrong, NAT is a remarkable improvement over prior serologic testing; for example, hepatitis C NAT has a window period of 3-5 days as compared to 70 days with traditional antibody (serologic) testing. NAT itself is a controversial topic since false-positive results can occur, and experts have raised concerns that this may result in unwarranted discard of organs. However in IRD donors NAT is a powerful tool for more accurate risk assessment. For example, donors with recent IV drug use with negative serological testing have a risk of undetected hepatitis C of 300.6 per 10,000 donors (3%). Having both negative serology and negative NAT reduces this risk to 32.4 out of 10,000 donors (0.3%).

To summarize: the U.S. is facing an epidemic of drug-overdose deaths. Simultaneously, there is a long list of patients waiting for a life-saving heart, kidney, lung or liver transplant. These two issues have become intertwined. It is an unsettling topic of discussion, but it behooves us to counsel patients that organ transplants from “increased risk” donors are non-inferior and improve survival.

Wei Ling Lau Headshot

Wei Ling Lau, MD is Assistant Professor in Nephrology at University of California-Irvine. She is currently funded by an AHA Innovative Research Grant, and has been a speaker for CardioRenal University and the American Society of Nephrology. Follow her on Twitter @Kidneys1st