Dec 16 2016

An injection of optimism into biomedical research – Part 1: Newborn screening success!

by at 1:03 pm

With headlines questioning whether science is broken, the skyrocketing costs of drug development, the high rates of obesity, and the recent decrease (though by only 0.1 years!) in life expectancy in the US, it can be tough to be an optimist in biomedical research – gloom and doom lurk just about everywhere. This is doubly so for someone like myself who is both an innate and a trained pessimist, what with my training in Biostatistics. However, I have been coming across numerous examples of successes in biomedical research and public health implementation from the past 60 years, and therefore want to share them in a multipart series here – my first foray into blogging – in order to spread cheer and hope in time for the holidays.

Research is hard and the only problems we tackle are those for which no solutions have yet been found. There are reasons why no longer look for cures for smallpox and polio! The prevention of many infectious diseases is well recognized as a huge public health success. I want to shed a bit more light on quieter success stories – There are many other examples which, though not as dramatic, show that science works and for many lesser known diseases that nonetheless affect many people in total, there is less suffering and more hope. I will be focusing on US examples, because these are the ones I am most familiar with, and welcome other examples in the comments.

Newborn screening programs for congenital diseases are valuable public health interventions, currently implemented in every state in the US – though the exact diseases considered are different in each state – and many other countries around the world via a blood test performed shortly after birth. In case of a positive result for one of the screened diseases, follow-up testing is performed to confirm the presence of the disease. The “poster diseases” for screening are phenylketonuria (PKU) – a recessive disease affecting 1 in 13,000 births – and congenital hypothyroidism (CH) – affecting 1 in 4000 births – for which screening has existed since the 1960s, respectively 1970s. In the absence of management, they both generally result in severe intellectual disabilities along with other potential health issues. The impact of these diseases can now be functionally eliminated via, respectively, a restricted diet, and a hormone supplement, both of which must be started shortly after birth. To give an idea of the human cost, consider the writer Pearl Buck, a novelist who won the Pulitzer prize in 1932 and became the first American woman to win the Nobel Prize for Literature in 1938. Her daughter Carol, born in 1920, had PKU and was institutionalized for most of her life. Part of the reason why she wrote her famous novel “The Good Earth” was to help pay for her daughter’s care. She would also write to her friend Polly Small “I would gladly have written nothing if I could have just an average child in Carol. Average children seem such a wonderful joy to me – I wouldn’t ask for a clever, bright child if I could have had her just average.” Buck would later publish the book “The Child Who Never Grew” in 1950, which is considered one of the first books to openly discuss intellectual disability.

Newborn screening panels are actively evolving, with a Recommended Uniform Screening Panel developed by the Secretary’s Advisory Committee on Heritable Disorders in Newborns and Children (SACHDNC) of the Department of Health and Human Services currently encompassing 34 core conditions. In general, diseases are included only if a treatment or management plan is expected to substantially alter the disease course if started before symptoms appear – this can be a difficult evidence-based medicine question and as such there is not always complete agreement. Other biomedical and ethical concerns – also see here and here – including issues such as:

  • Does the screening test have good performance in terms of false positives and false negatives? What are the costs of a false positive?
  • Should screening be performed for diseases without treatment or for carrier status so that families could be informed of risk to future pregnancies or be prepared for caring for a special-needs child?

While more work needs to be done in this area (I wouldn’t be a researcher if I didn’t end on this note), it is important to keep in mind that many children are already being substantially helped by this screening. In 2014, 3,988,076 babies were born in the US, which means that approximately 1,300 lives were fundamentally transformed by CH and PKU screening alone.


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Mar 09 2017

An injection of optimism into biomedical research – Part 5: Millions of babies

by at 3:59 am

This is the fifth and last part of my Injection of Optimism into Biomedical Research Series. I’m getting back to the babies on this one! In Part 1, I talked about the success of newborn screening programs, here I will be discussing a prenatal public health intervention that has saved and helped millions of babies worldwide.

The Rh protein complex is embedded in the membranes of red blood cells. Most individuals are Rh positive (Rh+), which means that their Rh complex contains a specific protein (the RhD antigen); individuals without that protein are Rh negative (Rh-). Approximately 15% of Caucasians, 7% of blacks, and 1% of Asians are estimated to be Rh-. Blood types are generally denoted by a shorthand reporting the ABO blood group and Rh status.  For example, an individual who has an ABO blood group of B and is Rh- is often denoted as “B-.” The Rh type is inherited in a recessive manner, so that a child who is Rh- must have two Rh- parents, but a child who is Rh+ may have two Rh+ parents or one Rh+ and one Rh- parent.

Problems can result if an Rh- woman is pregnant and carrying an Rh+ baby. In that case, the woman’s body may create antibodies to the RhD protein in the baby’s blood. These antibodies can destroy the baby’s red blood cells, leading to severe anemia or even death. This is called “Rh incompatibility” and generally occurs after the first pregnancy, since the first baby is usually born before the development of too many antibodies. In 1960, Rh incompatibility and the resulting hemolytic disease of the newborn (erythoblastosis fetalis) was estimated to result in 10,000 stillborn babies and even more babies who were affected and generally expected to recover after blood transfusions. In 1968, two clinical trials showed that injection of the anti-Rh gamma globulin (RhoGAM) after the delivery of an Rh+ baby by an Rh- woman will prevent problems with later pregnancies. Women who are at risk of Rh incompatibility now generally receive the RhoGAM shot at 7 months and within 72 hours of delivery, as well as in the case of miscarriage or bleeding during pregnancy.

Given that Rh incompatibility used to lead to many cases of perinatal death and illness and is now a rare concern if the RhoGAM shot is appropriately administered, this is a major public health victory. I hope this series as a whole will help renew your optimism and sense of wonder in biomedical research and science in general. Now let me get back to writing that grant proposal…

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Mar 06 2017

An injection of optimism into biomedical research – Part 4: Cancer prevention and early detection

by at 4:13 pm

This is the fourth part  of my Injection of Optimism into Biomedical Research Series. Since I am faculty at the Lombardi Comprehensive Cancer Center, I wanted to have a cancer-related post!

The use of Papanicolaou (Pap) tests for cervical cancer prevention and early detection has been an essential aspect of gynecological care in the United States since the 1950s. Recently Pap tests have been supplemented by the use of viral genotyping tests for the types of human papilloma virus (HPV) which cause essentially all cervical cancers as well as by the HPV vaccine (co-invented by Georgetown’s own Dr. Schlegel!). Given the huge decrease in cervical cancers due to the introduction of the Pap test, it is hard to remember that in the 1940s cervical cancer was a major cause of mortality for young women in the US – it is now only the 14th most frequent cancer in American women while still being a major driver of mortality in many parts of the world – globally it is the 4th most common female cancer and the 2nd most common in the developing world. Improved adoption of screening and vaccination practices are on their way to changing this picture. Since HPV also causes certain types of head and neck cancers in both men and women, HPV vaccines may play an even larger role in cancer prevention in the future.

An important note about cervical cancer: Recent work has shown that both the incidence and mortality rates and the disparities between these outcomes for black and white women are higher than had been previously estimated, particularly for older women, due to the inclusion of women who had had hysterectomies – which generally include removal of the cervix – in the denominator. There is still much work to be done, but the type of tools available for cervical cancer prevention and early detection would be a dream to researchers in other cancer fields!

Hepatocellular carcinoma (HCC) – the most common type of liver cancer – is generally the result of chronic infection with hepatitis B virus (HBV) or hepatitis C virus (HCV); a 2006 study led by the CDC estimated that 78% of cases worldwide can be attributed to these two viruses, which can also lead to a variety of other problems such as cirrhosis. Over the past couple of decades, the incidence of HCC has been increasing in the US, with approximately half of the extra cases between 1975 and 2007 being due to the increase of older individuals with chronic HCV. HCV was only discovered in 1989 and screening of donated blood and organs for this virus only became available in 1992. Since infected blood was a common source for HCV transmission before that time, the CDC recommends that all adults born between 1945 and 1965 be tested for HCV regardless of other risk factors, given that those individuals are five times as likely to be infected compared to other adults and an estimated 45%-85% of HCV-positive individuals are not aware of their status. A number of highly effective treatments for HCV now exist; the primary challenge right now is the high price of the drugs, which often leads to their use being limited to a subset of infected individuals, such as those who already have advanced liver disease.

The situation is somewhat simpler for HBV compared to HCV, as an effective vaccine exists, which is now part of the standard childhood vaccine schedule recommended by the CDC. Consequently the incidence of HCC can be expected to have a substantial drop over the next few decades. I mentioned in Part 1 of this series that I would not discuss the prevention of infectious diseases via vaccination in this series. When talking about cancer prevention though, I could not help but highlight the astounding fact that yes, there are vaccines against specific cancers!

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Jan 10 2017

An injection of optimism into biomedical research – Part 3: From deadly to chronic

by at 11:09 am

The first two parts of my Injection of Optimism into Biomedical Research series can be found here and here.

This part concerns a disease that was once considered deadly and is now considered generally chronic, Addision’s disease. Though somewhat obscure, this disease has affected many, including several noteworthy individuals. A more recent example of the deadly to chronic improvement process is HIV/AIDS, as increasing evidence is accumulating that the life expectancy for infected individuals in the developed world is approaching that of uninfected individuals – for example, see here and here.

Addison’s disease, first discovered in 1849, refers to reduced levels of adrenal hormones – such as cortisol – due to damage of the adrenal glands, usually of autoimmune origin, but also possibly due to a variety of other ailments such as tuberculosis and cancer. It is estimated to affect slightly more than 1 in 10,000 individuals. It can lead to low blood pressure, fatigue, weakness, and pain, with loss of consciousness and death possibly occurring during the severe “adrenal crises.” Before the introduction of glucocorticoid replacement therapy in 1938, this disease had a 2 year mortality rate of 80% and a 5 year mortality rate of 100% from the time of diagnosis. After the synthesis of hydrocortisone in the late 1940s, outcomes truly started turning around, although morbidity and mortality are still higher than in the general population, partly due to the side effects of chronic glucocorticoid use.

As an example of how the course of this once deadly disease was changed, consider two famous sufferers: Elizabeth Catez, a young French Carmelite nun and mystic, recently canonized as Saint Elizabeth of the Trinity, and President John F. Kennedy. Elizabeth died in 1906 at the age of 26 after being diagnosed with Addison’s three years prior. Her experience with the disease, especially the later stages, was so excruciating that it led her to develop a “mystical theology of suffering” and to write that Christ “wishes me to be the surrogate human being in whom he can suffer again for the glory of the Father and the salvation of the Church. This thought makes me so happy.”

The improvements made in disease management in the decades after Elizabeth’s death enabled JFK to keep his disease under control via the use of glucocorticoid treatment. There was much speculation during his life and his physicians always failed to either confirm or deny that he suffered from Addison’s disease. In 1967, after the president’s tragic 1963 assassination, Dr. John Nichols of the University of Kansas Medical Center provided evidence for the conclusion that JFK not only probably suffered from Addison’s, but had in fact also been case No. 3 in a 1955 study on the management of Addison’s disease during surgery. This was confirmed in 1992 when JAMA was able to establish this on the record with both hospital officials and the lead author of the 1955 paper.

Current treatment for Addison’s still relies on replacing the missing hormones, for example by substituting cortisol by hydrocortisone, prednisone, or dexamethasone, along with possible dietary interventions and the management of potential side effects of corticosteroid treatment, such as osteoporosis. Adrenal crises require immediate intervention and often involve giving the hormones as injections. Guidelines also exist for managing specific problems, such as surgery, illness or injury, and pregnancy, enabling those affected to live a much fuller life than was ever possible before.

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Dec 27 2016

An injection of optimism into biomedical research – Part 2: Improved management for two textbook diseases

by at 8:54 pm

This is Part 2 of my Injection of Optimism into Biomedical Research Series.  To read Part 1, click here.

Two diseases which have not (yet) been virtually eliminated – as phenylketonuria and congenital hypothyroidism have – but for which sufferers have seen huge benefits from early diagnosis and improved management are cystic fibrosis (CF) and sickle cell disease (SCD). Both of these diseases are caused by mutations in a single gene and inherited in an autosomal recessive manner. Though rare overall, they are among the most common genetic disorders in the world. As such, they are often “textbook examples” in introductory genetics classes. They are both now included in newborn screening programs in all 50 US states.

CF is present in 1 in between 2.500 and 3,500 births in Caucasians in the US, being the most common life-limiting genetic disorder amongst Caucasians. It leads to damage to multiple organ systems through the buildup of sticky mucus due to an abnormality in a chloride channel. In particular, it can result in severe nutritional and respiratory problems. While no curative treatment exists for this still-devastating disease, improved management has played a huge role in both quality of life and lifespan. This includes dietary recommendations to prevent malnutrition, therapeutic approaches to clear out the airways from thick secretions, and proactive use of antibiotics for treating airway infections. It is difficult to precisely understand the effect of this improved management on life expectancy, as when CF was first recognized as a stand-alone disorder in 1938 it was through autopsies of malnourished infants who had a life expectancy of 6 months. Less severe cases started being identified in the 1950s with the introduction of standardized “sweat tests” which led to comprehensive programs and improved survival. The responsible gene was finally identified in 1989. In the early 1970s the life expectancy for these “milder” cases was only in the teens, increasing to 25 years in 1985 and 37 years in 2008. There is increased hope that targeted gene therapy will provide a curative treatment, and the progress obtained in the last few decades must still not be overlooked.

SCD is a group of disorders which are characterized by hemoglobin – the protein in red blood cells that carries oxygen from the lungs throughout the body and returns carbon dioxide back to the lungs – having an abnormal and stiff shape. This leads to red blood cells (RBCs) which are sickle shaped instead of the usual flexible disc shape. The abnormal RBCs can stick to the vessel walls, leading to a lack of oxygen in surrounding tissues. This can result in severe “pain crises,” as well as anemia, increased susceptibility and impaired response to infections, and progressive organ damage.  SCD is the most common inherited blood disorder in the US and occurs in 1 in 365500 African Americans. The use of screening and other management strategies in early childhood, including penicillin prophylaxis and pneumococcal vaccines have led to an increase in life expectancy from < 20 years in the 1970s to the 30s or 40s since the early 1990s. Adult patients may also be prescribed hydroxyurea, which may reduce the frequency of the pain crises and the need of blood transfusions – this medication was initially approved in 1967 by the FDA to treat cancer and received a new indication for SCD in 1998 and is thus a great example of drug repurposing.

As the sickle cell trait is associated with protection against malaria when the disease-causing allele is present in a single copy, SCD is also very common in sub-Saharan Africa, estimated to affect 3% of all births in some regions. Indeed, it appears to be a major but often ignored cause of early childhood mortality, with some estimates ranging from 50-90% of individuals with SCD dying in early childhood and SCD accounting for 5-16% of under-5 mortality in certain regions. Similarly to CF, there is hope in using modern targeted approaches, including CRISPR, however the impact of improved management has been tremendous and indeed, its adoption in sub-Saharan Africa could substantially lower childhood mortality. Even in the US, there are limitations in terms of access to care for many SCD patients, meaning that improving overall management could improve outcomes even further.

Acknowledgment: Dr. Jacob Corn from UC Berkeley, the senior author of this paper on using CRISPR for SCD, was a keynote speaker at the 2016 ICBI Symposium. I learned a lot about SCD from talking to him, which made it very easy for me to look up the references for the second part of this post.


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Jul 07 2016

Bioinformatics is a vocation. Not a job.

by at 10:57 am

Bioinformatics is at the heart of modern day clinical translational research. And while experts define this as an interdisciplinary field that develops and improves methods and tools for storing, retrieving, organizing, and analyzing biological (biomedical) data – it is much, much more!

Bioinformatics helps researchers connect the dots between disparate datasets; improve extraction of signal from noise; predict or explain outcomes; and improves acquisition and interpretation of clinical evidence. Ultimately, it allows us to tell the real data stories.

To effectively tell these stories, and to see this all-encompassing domain in biomedical research and its true super powers, we must pursue bioinformatics as a vocation – or a calling – and not just a job.

Spring’16 has been a busy season for us Bioinformaticians at the Georgetown ICBI. I carefully curated six of our recent impact stories that you may find useful.

  1. AMIA’16 – The perfect triangulation between clinical practitioners, researchers and industry can be seen at AMIA annual conferences. I was honored to chair the Scientific Planning Committee for this year’s AMIA Translational Bioinformatics (TBI) Summits, featuring sessions on the NIH Precision Medicine initiative, BD2K program, and ClinGen. I sat down with GenomeWeb’s Uduak Grace Thomas for a Q&A on this year’s Summit, which attracted over 500 informaticians. Come join us at the AMIA Joint Summits 2017 to discuss the latest developments in Bioinformatics.
  1. Cyberattack Response! – We were in the middle of responding to NIH’s request for de-identified health record data for our Precision Medicine collaborative when MedStar Health, our health care partner’s computer systems, were crippled by a cyberattack virus. Thousands of patient records were inaccessible and the system reverted to paper records, seldom used in modern hospital systems. Thanks to the hard work and dedication of the IT staff, MedStar Health systems were restored within days with no evidence of any compromised data, according to the MedStar Health spokesperson. However, our research team had to act fast and improvise a way to fulfill the NIH’s data request. We ended up providing a complete synthetic linked dataset for over 200 fields. As our collaborator Josh Denny, a leader in the NIH Precision Medicine Initiative put it – “this experience you had to go through will help us be better prepared for research access to EHRs for nationwide clinical networks”. We sure hope so!
  2. Amazon Web Service (AWS) – The AWS Public Sector Summit was buzzing with energy from an active ecosystem of users and developers in federal agencies, small and large businesses, and nonprofit organizations—a community created over just the past few years. It was enlightening for me to participate on a panel discussing Open Data for Genomics: Accelerating Scientific Discovery in the Cloud, with NIH’s Senior Data Science Advisor, Vivien Bonazzi, FDA’s former Chief Health Informatics Officer, Taha Kass-Hout and AWS’s Scientific Computing Lead, Angel Pizarro. Three take homes from the Summit – (1) a growing need for demand-driven open data; (2) concern over the future administration’s commitment (or lack thereof) to #opendata; and (3) moving beyond data storage, and the future of on-demand analytics.
  3. Massive Open Online Course (MOOC) on Big Data – Want to begin demystifying biomedical big data? Start with this MOOC – to be available through Open edX late Fall. Georgetown University was recently awarded a BD2K training grant to develop an online course titled “Demystifying Biomedical Big Data: A User’s Guide”. The course aims to facilitate the understanding, analysis, and interpretation of biomedical big data for basic and clinical scientists, researchers, and librarians who have limited/no significant experience in bioinformatics. My colleagues Yuriy Gusev and Bassem Haddad, who are leading the course, are recording interviews and lectures with experts on practical aspects of use of various genotype and phenotype datasets to help advance Precision Medicine.
  4. Know Your TumorSM – Patients with pancreatic cancer can obtain molecular tumor profiling through the Pancreatic Cancer Action Network’s Know Your TumorSMprecision medicine initiative. It is an innovative partnership with Perthera, a personalized medicine service company that facilitates the multi-omic profiling and generates reports to patients and physicians. Check out the results from over 500 KYT patients presented at AACR’16 by our multi-disciplinary team of patient coordinators, oncologists, molecular diagnostic experts and data scientists.
  5. Moonshot – Latest announcement from VP Biden’s Cancer Moonshot program unveiled a major database initiative at ASCO’16. I had the opportunity to comment in Scientific American on the billions of bits of information that such a database would capture to help drive an individual’s precise cancer treatment. Continue to watch the Moonshot program if you are involved with cancer research or care continuum.

It is personally gratifying to see Bioinformaticians, BioIT professionals, and data scientists continue to solidify their role as an integral part of advancing biomedicine. I have yet to meet a bioinformatician who thinks of her/his work as just a job. Engage your bioinformatics colleagues in your work, we will all be better for it!

4 responses so far | Categories: From the director's office,Newsletter,Subha Madhavan | Tags: , , , , , , , , , , ,

Jan 19 2016

Cancer ‘Moonshot’ needs Informatics

by at 10:33 am

Many of us who work in the interface of Cancer Clinical Research and Biomedical informatics were thrilled to hear about the cancer moonshot program from President Obama announced in his final State of the Union Address on Tuesday, Jan 12’16.

VP Biden, the nominated leader for this effort, has pledged to increase the resources available to combat the disease, and to find ways for the cancer community to work together and share information, the operative word being “share” (after ‘resources’).

In this post, I briefly review (by no means comprehensive; just a Saturday morning project while brunch cooks in the Instant pot) four thematic areas where informatics is already playing a key role to help realize cancer moonshot goals and identify challenges and opportunities.

  • Immunotherapies: Recent approvals of ipilimumab (Yervoy), sipuleucel-T (Provenge), Nivolmab (Opdivo) and Pembrolizumab (Keytruda) represent important clinical advances for the field of active immunotherapy in oncology and for patients with melanoma and prostate cancer, respectively. Immunoinformatics has played a critical role in B- and T- cell epitope prediction during the course of development of these therapies. New predictive computational models to describe the time-dependent relationships of cancer, immunity, and immunotherapies have emerged over the last few years. Using next gen sequencing approaches such as whole genome, exome and RNA sequencing, it is now possible to characterize with high accuracy the individual set of Human Lymphocyte Antigen (HLA) alleles of an individual patient leading to personalized immunotherapies. The biggest challenge in immunoinformatics arises from the routine sequencing of individual human genomes. We need new informatics tools to study the impact of natural genomic variation on the immune system and how to tap into it for new therapies. Click here for further reading.
  • Precision medicine: President Obama’s precision medicine initiative and the $215M investment have brought precision medicine to the forefront of many organizations. The cost of cancer care is estimated at $200 Billion each year and only on the rise as our population increases and lives longer. Many pundits see Precision Medicine as a way to deliver value-based cancer care. Thanks to high throughput technology, including genomic testing of each tumor, and each patient’s inherited DNA— along with proteomics in the future—oncologists are able to tailor regimens for gene mutations in each patient thus avoiding high cost of drugs that may not work. A key informatics challenge is to figure out which of the thousands of mutations in a patient’s tumor are drivers or actionable markers. There is a race in both academic and commercial space to develop software that will tease out the ‘drivers’ from the ‘passengers’. Furthermore, mutations have to be categorized by levels of evidence: high evidence – where the gene mutation has been tested in a randomized controlled trial (RCT) setting, medium evidence – retrospective gene mutation analysis of RCTs- and finally low level evidence with pre-clinical data only on the mutation. We need better evidence modeling approaches to categorize actionable mutations if clinicians are to use these in routine patient care. Click here for further reading.
  • Cell free DNA/blood tests: While molecular profiling in solid tumors remains routine practice in cancer diagnostics, modern technologies have enabled detection of biomarkers in stray cells, exosomes and traces of DNA in blood and other body fluids. This offers a low cost method to obtain cancer-profiling data for diagnosis and treatment when invasive tissue biopsies may be clinically difficult. While technologies and informatics methods for detecting very small amounts of tumor DNA are on the rise, there are many biological issues that need to be addressed. If the tumor cell did not shed a single piece of variant DNA, even the most sensitive technology will be unable to detect it. Commercial interest in this space is enormous. The Genomics/Informatics Company Illumina has just launched a new startup, GRAIL, in collaboration with Jeff Bezos and Bill Gates to develop a single blood test that could detect cancer early. Now, that is a moonshot goal! Click here for further reading.
  • Organizing cancer data: Now on to my favorite topic of organizing cancer data to power new discovery. Secondary use of EHR data for observational studies is improving through clinical research networks. As large biorepositories linked to electronic health records become more common, informatics is enabling researchers to identify cohorts that meet study criteria and have requisite consents.
    Modified from Thomas Wilckens, MD

    Modified from Thomas Wilckens, MD

    While there have been significant efforts in sharing molecular data sets publicly, less progress has been made on sharing healthcare data. Many standards exist today to facilitate data sharing and interoperability. We need more training of existing standards to consumers (app developers, scientists) of standards. We also need a comprehensive knowledgebase ecosystem that supports federated queries across cancer subtypes, risk, molecular features, diagnosis, therapy and outcomes at an individual level to advance biomarker discovery and better clinical decision support. Real-world Big Data on claims, outcomes, drug labels, research publications, clinical trials are now available and ready to be linked and analyzed to develop better cancer treatments. NCI’s TCGA and Rembrandt, Georgetown Lombardi Cancer Center’s G-DOC, Global Alliance for Genomic Health (GA4GH), ASCO’s CancerLinQ are all efforts in this direction. Let’s unleash cancer big data in effective ways to collectively make the moonshot program a reality! Click here for further reading.

Programs such as the cancer moonshot are a journey, not a destination and if directed appropriately, can inevitably better the practice of cancer medicine.

4 responses so far | Categories: From the director's office,Subha Madhavan | Tags: , , , , , , , , ,

Nov 03 2015

Quantified Self, GenomeFirst and a trip to the White House – A busy week for Biomedical informatics

by at 11:22 pm

“You are over pronating!” bleeps Bluetooth enabled, sensor-infused smart socks just 10 minutes into your daily running routine.

Or, “check your blood pressure, temperature and heart rate using Scanadusm, with no cuffs, in just 15 seconds!” quips Kevin Maloy of MedStar Institute for Innovation during our fourth annual Georgetown Biomedical Informatics Symposium on October 16, organized and hosted by the Innovation Center for Biomedical Informatics. Emerging trends in informatics and health IT were demonstrated and discussed with over 350 attendees from academia, industry and government. The event benefited from strong support of institutional and industry sponsors. Find out more about the symposium’2015 here. I present Cliff Notes version of four major themes here for your quick browsing.

  1. Quantified Self

We are increasingly wearing bands to track how much we move, strapping on watches to listen to our heartbeat, and logging what we eat and drink. The underlying proposal is that describing ourselves with these numbers will put healthcare back in the hands of people. Will the “quantified self” become a major driver in how diseases are prevented or treated? This is one of the intriguing questions that our symposium explored.

Informatics opportunity: Design in healthcare is an opportunity to improve signal and reduce noise in a system that is over stretched, under utilized and very expensive.

  1. EHRs and other emerging health technologies

Digitized health is a dream come true for many. But are electronic health records (EHRs) actually getting in the way of physician productivity? At our symposium, Mike Hogarth of University of California, Davis presented results from a survey of 410 internists that estimated that 42 minutes are lost each day by physicians due to EHRs. About 80% of key clinical data are in the form of unstructured narratives – a mess he referred to “dirta,” instead of data. This information requires enormous quality control, structuring, and integration – a reality that raises the question: can practice-based evidence be generated through retrospective studies of EHR datasets?

Informatics opportunity: Nigam Shah of Stanford University suggested that enterprise wide data governance at hospital systems, or a green button function within EHRs, could help clinicians use aggregate patient data to support decisions at the point of care. Ben Schneiderman of University of Maryland demo’ed EventFlow, a tool for visual analysis of temporal events within patient records to enable advanced healthcare discovery. Zak Kohane of Harvard University, in his keynote lecture, cited clinical research data integration software such as i2b2, tranSMART, and SMART Health IT apps as solutions to the “dirta” problem in healthcare innovation.

  1. Trends in Precision Medicine

A lot of the excitement at the symposium – amplified by the talks on targeted therapies in pancreatic cancers and a panel discussion on Next Generation Sequencing (NGS) in the clinic – was focused on Precision Medicine.

Mike Pishvaian of Georgetown University and Dr. Jon Brody of TJU discussed PANCan’s “Know your tumor” program. This program has found that 43% of patients had actionable findings from molecular profiling, resulting in modified treatment recommendations and better responses.

Regeneron’s Rick Dewey asked a provocative question: what if everybody’s genome was available in his or her medical record? Rick and Marc Williams of Geisinger described a collaboration between Regeneron and Geisinger to use EHRs and exome sequencing data from over 200,000 individuals for faster drug discovery. It was a treat to hearabout Geisinger’s GenomeFirst initiative, which is implementing genome inference engines – clinical decision support and predictive models to enable Precision Medicine in a unique way with teams of clinicians, genetic counselors, nurse practitioners and informaticians.

No scientific symposium is complete without an award! The (iPAD winning) best poster award went to Ao Yuan, graduate student in Biostatistics at GU for his work on a semi parametric model for the analysis of patient sub-groups in precision medicine trials.

The Precision Medicine journey is underway, and is already improving medicine. Informaticians are vital to this journey. More work is needed to collect the right patient cohorts for research, to identify the right markers to test, and to develop the appropriate targeted therapies.

The Symposium explored what’s next for all of us in this important journey?

Informatics opportunity: Curating evidence of biomarker association with drug response, novel data wrangling approaches to extract and analyze useful clinical and genomic data to drive new hypothesis generation and clinical decision support, and data science approaches to connect genotypes to phenotypes are a few of many opportunities for informaticians to meaningfully participate in the precision medicine revolution.

  1. Security, Privacy and Trust principles for patient-centered studies

The symposium was a perfect lead-in to a great roundtable discussion on a much-needed security framework for President Obama’s Precision Medicine Initiative at the White House OSTP. I was humbled by the discussion with experts in cyber security, patient privacy, trust principles, and data breach. Will “white hat hacking” help? How can we use it in the context of protecting healthcare data and participants from willful misuse?

Informatics opportunity: DJ Patil, US Chief Data Science Officer emphasized the need for IT teams to focus on data infrastructure, auditing and monitoring of patient genomic data, data transmission and access infrastructure, including tiered data access.

It is so gratifying to see informaticians providing thought leadership across the full spectrum of clinical research and care. Let’s continue the conversation – find me on e-mail at or on twitter at @subhamadhavan.

7 responses so far | Categories: From the director's office,Newsletter,Subha Madhavan,Symposium | Tags: , ,

Aug 07 2015

Practical Precision Medicine: Striving for Better Medicine

by at 12:33 pm

Practical Precision Medicine is about striving for better medicine. But it means different things to different people.

For patients, it promises fewer “trial and error” therapies and fewer side effects, especially fatal ones. The New England Journal reported the tragic case of a 2-year old boy with obstructive sleep apnea who underwent a routine, outpatient adenotonsillectomy. After an uncomplicated surgery, the parents were sent home with a prescription for acetaminophen with codeine. Unknown to the physicians, he had a functional duplication of the CYP2D6 allele, the enzyme that turns codeine into morphine. Practically, this resulted in a lethal dose of morphine in his blood. If a genetic test for this were available in the right place, at the right time, could it have prevented this tragedy?

For patients, practical precision medicine also means new therapies and hope.

Case in point, the remarkable story of one woman’s ordeal with pancreatic cancer detailed at Georgetown’s Lombardi Cancer Center website. When standard chemotherapy failed, genetic testing identified an experimental therapy (PARP inhibitor) that made her cancer disappear.

For providers, Precision Medicine is somewhat of a mixed bag. Some of this genetic testing is old news. For years they have been testing for Prothrombin mutationFactor V Leiden or HIV 1 genotype. In this case, it is not called Precision Medicine; it is simply called routine clinical practice.

The challenge for clinicians lies in the evidence that Precision Medicine directly improves outcomes. Examples of therapies that made sense, were widely used, and then proved harmful (for example hormone replacement therapy to prevent first heart attack or stroke) litter the history of medicine. There are always more tests to order. However, the issue is determining which tests pass beyond the standard of “it makes sense it should work” and actually improve outcomes when studied in a rigorous manner.

The Precision Medicine journey has already begun, meaning different things to different individuals but inevitably bettering the practice of medicine.

By Subha Madhavan, PhD & Kevin Maloy, MD, 2015

*Post originally appeared on MedStar Institute for Innovation (MI2) blog site 

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Jun 14 2015

Health Datapalooza ’15

by at 12:30 pm

It was a treat to all data enthusiasts alike! What started out five years ago with an enlightened group of 25 gathered in an obscure forum has morphed into Health Datapalooza which brought 2000 technology experts, entrepreneurs and policy makers and healthcare system experts in Washington DC last week. “It is an opportunity to transform our health care system in unprecedented ways,” said HHS Secretary Burwell during one of the keynote sessions to mark the influence that the datapalooza has had on innovation and policy in our healthcare system. Below are my notes from the 3-day event.

Fireside chats with national and international leaders in healthcare and data science were a major attraction. Uhealthdatapalloza.S. Chief Data Scientist DJ Patil discussed the dramatic democratization of health data access. He emphasized that his team’s mission is to responsibly unleash the power of data for the benefit of the American public and maximize the nation’s return of its investment on data. Along with Jeff Hammerbacher, DJ is credited to have coined the term data science. Most recently, DJ has held key positions at LinkedIn, Skype, PayPal and eBay. In Silicon Valley style, he said that he and his team are building a data product spec for Precision Medicine to drive user-centered design, he quoted an example of such an app, which will provide allergy-specific personalized weather based recommendations to users. Health meets Climate!

Responsible and secure data sharing of health data is not just a “nice to have” but is becoming a necessity to drive innovation in healthcare. Dr. Karen DeSalvo, the Acting Assistant Secretary for Health in the U.S. Department of Health and Human Services, is a physician who has focused her career toward improving access to affordable, high quality care for all people, especially vulnerable populations, and promoting overall health. She highlighted the report on Health information blocking produced by the ONC in response to Congress’s request. As more fully defined in this report, information blocking of electronic healthcare data occurs when persons or entities knowingly and unreasonably interfere with the exchange or use of electronic health information. The report produced in April lays out a comprehensive strategy to address this issue. She also described early successes of mining of social media data for healthcare describing the use of Twitter to predict Ebola outbreak. Lastly, she shared a new partnership between HHS and CVS on a tool that will provide personalized, preventive care recommendations based on the expert recommendations that drive the MyHealthFinder, a tool to get personalized health recommendations.

There was no shortage of exciting announcements including Todd Park’s call for talent by the U.S. Digital Service to work on the Government’s most pressing data and technology problems. Todd is a technology advisor to the White House based in Silicon Valley. He discussed how the USDS teams are working on problems that matter most – better healthcare for Veterans, proper use of electronic health records and data coordination for Ebola response.  Farzad Mostashari, Former National Coordinator for Health IT, announced the new petition to Get my Health Data – to garner support for easy electronic access to health data for patients. Aaron Levine, CEO of Box described the new “platform” model at Box to store and share secure, HIPAA-compliant content through any device. Current platform partners include Eli Lily, Georgetown University and Toyota among others.

An innovative company and site ClearHealthCosts, run by Jeanne Pinder, a former New York Times reporter for 23 years, caught my attention among software product demos. Her team’s mission is to expose pricing disparities as people shop for healthcare. She described numerous patient stories including one who paid $3200 for an MRI. They catalog health care costs through a crowdsourcing approach with patients entering data from their Explanation of benefit statements as well as form providers and other databases. Their motto – “Patients who know more about the costs of medical care will be better consumers.”

Will the #hdpalooza and other open data movements help improve health and healthcare? Only time will tell but I am an eternal optimist, more so after the exciting events last week. If you are interested in data science, informatics and Precision Medicine don’t forget to register for the 4th annual ICBI Symposium on October 16. More information can be found in this Newsletter. Let’s continue the conversation – find me on e-mail at or on twitter at @subhamadhavan

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