Robert M. Califf, MD

When you blush, your stomach lining also reddens.
A Sobering Reminder from Nature

Nature, a prominent bioscience journal, just publishing an editorial warning PCORI about the hazards of developing a national data infrastructure ( The article is sobering, but also encouraging. The major advance from PCORnet will come from combining the rapidly evolving data and informatics world, the energetic panoply of researchers who are so motivated to answer questions and the patients themsleves. It is the patients and their advocates who stand the best chance of helping us find the balance between protecting privacy and advancing knowledge, between autonomy and the commmon good and between trust in the wisdom of clinical practice and admitting the uncertainty of our current recommendations. The adventure is already a major learning exercise and it is becoming more intense as more people get interested.

The Status of the US in Health and Health Care

The rhetoric has heated up again about the health status of the US population and the role of the organized delivery system in fixing the problem. On Fareed Zacharia’s GPS ( on CNN, Michael Porter’s latest ranking showed the US at 60th among countries for health and wellness. This doesn’t square with the view most Americans have of our country, yet the population statistics are compelling that we have work to do as a society.

Much of the our poor standing derives from cultural issues that lead people to do self-destructive behaviors with diet, exercise, substance abuse and violence. And the increasing focus on income inequality with its basis in educational disparities provides ample room for arguing that this is not a healthcare delivery issue. On the other hand, our integrated healthcare delivery systems (otherwise known as academic health and science systems-AHASs), particularly those with a large university base, have become the largest economic engines in many parts of America.

Is there a way to harness the power of informatics, the reach of our healthcare systems into neighborhoods and the integration with the knowledge engine of univerisities in order to change this equation?

The PCORnet Challenge

The development of PCORnet has been every bit as fascinating and challenging as expected. The concept of 29 networks involving between 11 and 100 million Americans is breathtaking. The socialization is still ongoing, as the many involved participants are just beginning to get to know each other.

One of the many fascinating issues is the fragmentation of the clinical research communities. Each fragment has its own view of the world, including special nomenclature and often, different meanings for the same terms. One of the most important of these divisions is the world view of informaticians and clinical investigators–this was symbolized by the fact that the AMIA meeting was held in San Francisco at the same time the Association for Clinical and Translational Science and the Clinical Research Forum were held in Washington.

Despite these issues and much fatigue from long days, the spirits of the group remain great, and it’s inspiring to see the different sectors working to overcome schisms for the common purpose. Part of the fun for me will be to see if we can shape an institution to help by providing a model and a pipeline of talent for this national purpose of creating a learning health system.

Research Permissions–Angels on the Head of a Pin, or the Key Issue to Decipher?

NEJM today has a pair of sentinel papers on the issue of research permissions for comparing therapies already in routine use in practice. Ruth Faden, Nancy Kass and colleagues from Hopkins, building on the ir Learning Health System work featured in the Hastings Center Reports, argue that in a proper context specific informed consent is not needed. Scott Kim and Franklin Miller from NIH argue that consent is needed, but that current circumstances call for a very different approach that integrates information needs in clinical care with knowledge acquisition through randomization. In their approach the consent would be very short and consistent with a fabric of information already given to people about what is known about the care they are receiving and the choices being made by the patient and provider.

The exciting element of the pair of articles is that the agreement is much greater than disagreement. Both groups of ethicists agree that the current approach is not optimal. In discussions about this issue, many colleagues have pointed out to me how seldom we really inform people about the uncertainties of current clinical recommendations. Over 85% of decisions in cardiovascular disease are not based on high quality evidence and other specialties have even a lower rate.

I hope these articles will move people to a better place that might include:

1. much better information in practice about what we really know (evidence based medicine) vs our opinions (opinion based medicine) and a better characterization of the uncertainty
2. notification and consent that doesn’t treat randomization as a major event, but rather as a tool to help inform us all about what we should do to optimize health

A colleague recently said: “When you get offered the next procedure where the evidence is unclear, maybe you should be asked: “Would you rather that I guess whether this procedure is good for you, not tell you that the doctor next door would do something different and do the procedure with a promise that we will learn nothing that will give the next patient a better chance? Or would you rather enter a study in which we let you know about our uncertainty and learn about the procedure so that all future patients can benefit?”.

A Tipping Point?

In the past 48 hours I have been involved in many meetings and discussions about learning, health decisions and healthcare. Ray Gibbons, a former Duke fellow who went on to greatness at Mayo Clinic and was President of the American Heart Association, pointed out that we could save a million lives if we just implemented systems that made sure effective therapies were given. On many conference calls and discussions, patient advocates and researchers were realizing that the evolving texture of health system data would give us the ability to intelligently provide useful information about choices to patients in the near future. Liberating us from the ignorance that comes from the isolation of practitioners as they try to learn from their own limited experience will be a major advance in medical history. Even as we struggle trying to put data into cumbersome systems like EPIC we are beginning the see the fruits of our labor as patterns emerge in data that guide better decision making. The invigoration of administrators and clinicians, now armed with information, is leading to fascinating discussions about the boundaries (or lack thereof) between quality improvement and research involving human “subjects” (also known as participants!).

The outcome seems inevitable– much better decisions made by patients and clinicians armed with better and better data. The question is: when will we reach the tipping point and what can we do to reach that point more quickly?

The Human Being as the Target for Study

AS we are reviewing our efforts to use modern technologies to advance our knowledge of: 1) human biology; 2) the impact of new and old interventions on human biology, it has become increasingly clear that we are not configuring our enterprise optimally. In most of our country’s best academic centers we have expertise in gene sequencing, genomic technologies, imaging, pharmacology and informatics. And in pharma and biotech, the success rate remains miserable and surprises continue to occur in late phases. Yet, we just haven’t organized our resources to optimize knowledge acquisition. Academic centers are not well organized and pharma continues to use cookie cutter phase I designs.

The recent work of Geoff Ginsburg and multiple colleagues at Duke is demonstrating that taking a new look at old problems (aspirin dosing and infection detection) provides a different view of health and disease than we had expected. Mike Snyder’s work at Stanford shows the same when intensive measurements are applied to an individual. Cancer continues to evolve to a view that pathways may be as important, or more important, than organ specificity when it comes to therapy and prognostic stratification.

Is it time to reconfigure? How do we do it without recapitulating the issues that led to the dissolution of the old GCRC system?


What is a Research Site?

We are accustomed to thinking of a research site as a clinic or a unit in a hospital. In the past 48 hours I have had the chance to speak with leaders of the PCORnet based consortia for “research sites” that include the city of New York, the city of Chicago and seven states in the midwest. I believe that we’re going to need to think of a new nomenclature in an era in which clinics and hospitals are owned by integrated health systems which roll up into regional consortia. The entire infrastructure support will be different if this approach succeeds.

Building a National Network–Early Phases

We’re having a very interesting time meeting the leaders of 11 Clinical Data Research Networks (CDRNs) and 18 Patient Powered Research Networks (PPRNs) selected through peer review for PCORnet. The amount of talent, technological sophistication and desire to make a difference is impressive. The CDRNs will provide massive involvement of integrated health systems and their patients across the spectrum of health and disease, while the PPRNs will provide a deep set of data and commitment from patients and families with particular diseases and/or medical problems. The intersection of these 2 types of networks into the “network of networks” will be fascinating.

While the potential is obvious, the complexity and lack of coordination is the major challenge. So much of our clinical research infrastructure is either isolated from resources that could enhance the effort, and the approach of building a clinical trial, getting a result, taking down the trial system and starting over with the next one is insane!

This is our chance to move the clinical research enterprise to a new level, and much of the fun of it will be the combustible mix of people with so much talent who have not worked together before. The product is likely to be something that we could not have predicted.

A New Year with Great Opportunity for Researchers

I believe that 2014 will be the year in which a transformation happens in the 2 big spheres of clinical research: intensive human biology and clinical studies involving cohorts and populations. A major shift to a new data fabric of electronic health records, registries and data derived directly from people/patients from personal devices will begin to supplant traditional stand alone data systems. This change will trigger a reformation of clinical epidemiology and physiology as we apply big data methods to reclassify disease and understand biology, and it will be applied to populations. The population component will lead to a fusion of observational studies, clinical trials and epidemiology to a common discipline applying different methods on top of a new information infrastructure. The launching of the PCORnet ( will be one major example, but other efforts will soon become apparent. These changes will not happen over the course of one year, but I believe that 2014 will be the tipping point.

Downtown Durham

I had the chance to hear about Duke Medicine’s plans to contribute to downtown Durham. The city has been through many phases, but what is happening now is quite amazing. An increasing number of our research and operations people are moving into renovated or new buildings in the old “tobacco and textile” town.

The trajectory is clear: a mixed model of business, academia, biotech, cultural and great food. It should be an economic and cultural engine for the region. The DCRI’s Durham Centre is a key part of the plan and the building is fantastic.

One question is whether we can use this engine to also improve the regional ambience in terms of education, health and participation in cultural advances.

© Robert M. Califf, MD. Blog design by Hopkins Design Group Ltd. HTML, CSS, and WordPress Theme by Digital Mettle, LLC.