Health Care, Analytics and Big Data

The evolution of electronic health records and health information exchanges is producing large amounts of data on disease, treatments, demographics and treatment outcomes. The data is beginning to expose unknown relationships between different diseases in the same patients.

An unlikely investigator is a  physicist from Vienna Austria.   Stefan Thurner is a physicist, not a biologist. But not long ago, the Austrian national health insurance clearinghouse asked Thurner and his colleagues at the Medical University of Vienna to examine some data for them. The data, it turned out, were the anonymized medical claims records—every diagnosis made, every treatment given—of most of the nation, which numbers some 8 million people.

Thurber reports in an article he authored in Quantia.

Network maps reveal hidden molecular connections between disparate diseases.In a recent paper in the New Journal of Physics, Thurner and his colleagues Peter Klimek and Anna Chmiel started by looking at the prevalence of 1,055 diseases in the overall population. They ran statistical analyses to uncover the risk of having two diseases together, identifying pairs of diseases for which the percentage of people who had both was higher than would be expected if the diseases were uncorrelated — in other words, a patient who had one disease was more likely than the average person to have the other. They applied statistical corrections to reduce the risk of drawing false connections between very rare and very common diseases, as any errors in diagnosis will get magnified in such an analysis. Finally, the team displayed their results as a network in which the diseases are nodes that connect to one another when they tend to occur together.

A human disease network maps out connections between diseases — if patients who have one disease tend to also have another, the two disease nodes are connected.

One disease module they’ve studied is for pulmonary hypertension (elevated BP in the pulmonary artery. The researchers published their findings in the journal Pulmonary Circulation.

Another module looks at Type 2 diabetes.   Researchers have linked diabetes to about 200 spots on the genome through genome-wide association studies.  We know genes have multi-factorial effects, but have less evidence for association in different diseases. Empirical clinical cases reveal a co-incidence of Type II  diabetes, and hypertension.  Mapping disease networks may explain more objectively the association between these two diseases.

The real promise is to reveal previously unknown associations of diseases.

This article was reprinted on ScientificAmerican.com.

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Today:   Many  patients do not  want to take daily medications, but will take nutritional supplements on a daily basis.

Many Willing to Die Months Earlier to Avoid Daily Meds: Survey

Tuesday: Advances in treating Cancer 

During the past decade treatment of cancer has evolved greatly. Wheras previously many toxic agents were used to kill cancer cells, along with radiotherapy, today there is a new class of agents, immunosuppresants, and targetted gene therapy. Immunotherapy uses the body's own protective antibodies to destroy a foreign antigen in a cancer cell.  Monoclonal antibodies are selectively produced against specific cancer cell lines. Pre-treatment genomics allows for individualized and personalized drug design.  

Progress        About Cancer.net      Navigating Cancer Care     

Types of Cancer     Coping and Emotions    

         Introduction to Cancer Research

Navigating Cancer Care

Explaining Cancer Genome Research

A growing area of cancer research, called cancer genome research, compares genes found in tumors and genes found in healthy tissue in order to understand how these genes differ and which ones are important. To do this, researchers collect samples from all types of tumors to find out a tumor’s genetic “fingerprint” and then compare it to the fingerprints of healthy tissue from the same person. Different genes are involved in different tumor types, and understanding what genes are important to the development of cancer may lead to improvements in detecting, diagnosing, and treating cancer.

About cancer and cancer genomes

Cancer begins when normal cells start to change and grow uncontrollably, forming a mass called a tumor. All of these changes take place at the most basic level of the cell—its genes. Genes are made up of deoxyribonucleic acid (DNA), which contains all of the chemical instructions that tell cells what to do and when to do it. When these instructions have mistakes, cells may not function normally. Sometimes these mistakes result in uncontrolled, abnormal cell growth and the ability to invade and spread to other tissues and organs in the body. This is the beginning of cancer.

All of the genes in a cancer cell are known as a cancer genome. Many of these genes are like those in healthy cells; however, a few genes have specific mutations (changes) that are responsible for turning a previously healthy cell into a cancer cell. While some of these mutations are inherited (passed down from your parents), most happen during your lifetime. Many of these changes occur as a result of being exposed to environmental factors, such as chemicals, or from lifestyle choices, such as smoking. Others appear to happen at random as cells divide.

Researchers are learning that different tumors have different mutations, even if the cancer started in the same organ. In other words, not all lung tumors or breast tumors have the same genetic fingerprint. There is also evidence that a recurrent cancer (a cancer that comes back after treatment) has different mutations than the original cancer. This variation is what makes treating cancer so difficult, but it is also what provides opportunities for new treatments.

If you have been diagnosed with cancer, you might have had some tissue removed in a biopsy. The biopsy sample provides doctors with information about the best way to treat your cancer. Now doctors often use additional tests to learn whether the tumor has specific mutations that may affect your treatment options. For example, ASCO recommends that a person with advanced non-small cell lung cancer have the tumor tested for the epidermal growth factor receptor (EGFR) when a doctor is considering giving a treatment known as a tyrosine kinase inhibitor (TKI).

The Cancer Genome Atlas project

One of the biggest efforts underway to understand the cancer genome is The Cancer Genome Atlas(TCGA) project. This project was started in 2006 by the National Cancer Institute and the National Human Genome Research Institute. The idea is to create a “map” of various cancer genomes in order to better understand what turns a normal cell into a cancer cell and what makes one cancer different from another.

As part of TCGA, researchers are collecting tissue samples from patients treated at cancer centers across the United States. By studying hundreds of these tissue samples and comparing them to tissue samples from people who do not have cancer, researchers are mapping the genomes of glioblastoma (a malignant brain tumor), lung cancer, and ovarian cancer. TCGA expanded the range of its research; find a complete list of all the cancer genomes that TCGA is mapping here.

In the first results mapping the glioblastoma genome, researchers found several mutated genes that are responsible for the development and growth of glioblastoma, including three genetic mutations researchers previously did not know were common in this type of cancer. This information may help researchers determine if patients with a particular gene that is mutated may benefit from treatments that target that gene but not from other treatments. Researchers also pinpointed a mutated gene that may cause chemotherapy to not work in some people with glioblastoma.

Another important finding from TCGA is that tumors from the colon and the rectum, judging by their DNA fingerprints, are really a single type of cancer, not two different cancers as previously thought. This information helps doctors better understand how cancer begins and may improve future treatment for people with this cancer.

What this means for patients

Although some results of cancer genome mapping may not be ready for use in cancer treatment today, discoveries from this research may lead to better tests to diagnose cancer and new treatments that are more effective. Talk with your doctor to learn more about the role of genes in cancer, including whether your tumor should be tested for mutated genes and if there are any treatment options that target those genes.

More Information

Understanding Targeted Treatments

Facts About Personalized Cancer Medicine

Understanding Pharmacogenomics

Drug Discovery and Development

Key Messages:

• Once a new drug has been identified, it is first tested in a laboratory to learn how it is used by the body, identify potential side effects, and figure out what doses are safe to use.
• If the results of laboratory testing suggest the drug is likely to be safe and effective, it will be evaluated in research studies involving volunteers, known as clinical trials.
• Once clinical testing is complete, the U.S. Food and Drug Administration (FDA) will review the results and may approve the drug if the evidence shows it is safe and effective. Then the drug can be made available to doctors and patients.

Doctors and scientists are always looking for better ways to treat people with cancer. To do this, they are constantly developing and studying new drugs, as well as looking for new ways to use existing drugs.

For a drug to go from being an idea in the laboratory to something that can be prescribed by a doctor, it must go through an extensive development and approval process to make sure it effectively treats cancer and is safe for people to take. Typically, this process takes many years and costs hundreds of millions of dollars. However, depending on the drug, the actual amount of time and money required varies.

Preclinical research: Drug discovery and initial testing

The discovery of new cancer drugs happens in a variety of ways.

Accidental discovery. In the early 1940s, an explosion exposed sailors to poisonous mustard gas. After observing that these sailors developed low white blood cell counts, doctors began using nitrogen mustard (mechlorethamine [Mustargen]) to treat Hodgkin lymphoma, a cancer of the lymphatic system involving the white blood cells. Mechlorethamine is still used as a cancer treatment today. Accidental discoveries such as this are rare, though.

Testing plants, fungi, and animals. Paclitaxel (Taxol), which is used to treat several types of cancer, was originally identified in the bark of the Pacific Yew tree. More recently, the drug eribulin (Halaven) was developed from a primitive animal called a sea sponge. The National Cancer Institute (NCI) has samples of thousands of plants, marine organisms, bacteria, and fungi collected from around the world in the hopes of discovering new cancer treatments.

Studying the biology of cancer cells. Currently, most researchers who are developing drugs to treat cancer start by comparing the genetics (DNA) and cellular processes of cancer cells to healthy cells. This information is used to identify important steps in the cancer development process that could potentially be altered by a drug. For example, researchers learned that approximately 20% of all breast cancers have an abnormal amount of a specialized protein called HER2 that controls the growth and spread of cancer cells. Four drugs that specifically target HER2 have been developed: trastuzumab (Herceptin), lapatinib (Tykerb), pertuzumab (Perjeta), and ado-trastuzumab emtansine (Kadcyla). Now, a person diagnosed with breast cancer has her tumor tested to check for HER2 to find out if these drugs can be used to treat the cancer. Learn more about these targeted treatments.

Understanding the chemical structure of a drug target. Scientists may use computers to simulate the interaction of a potential drug and its target, similar to fitting two puzzle pieces together. Using information from the computer models, researchers can then design chemical compounds that interact with the specific drug target.

Once potential drugs are identified, they are usually tested in human tumor cells in the laboratory to see if they are able to stop the growth of cancer cells. Next, the potential drug is tested in animals to confirm it is still effective at treating cancer. Typically, researchers test the drug in two or more different animal species. Testing in animals also helps researchers learn how the new drug is used by the body, what side effects the drug may cause, and what dose of the drug should be used in human research trials.

Drug developers and sponsors

The FDA does not develop or test drugs. Instead, pharmaceutical companies and other organizations, such as university medical centers and some government agencies (for example, the NCI) work to discover and test new drugs. The organization that develops a drug is called the sponsor. The sponsor conducts the research needed to provide the FDA with the necessary information to help them make decisions about drug approval.

Clinical research: Testing in people

Before new drugs are allowed to be taken by people, the sponsor must submit an Investigational New Drug (IND) application to the FDA. The IND contains the results of the preclinical (laboratory and animal) studies, plans for clinical (human) trials, and details about how the new drug is made. The FDA approves potential drugs for human testing if the preclinical research indicates the drug is likely to be safe and effective, if the proposed clinical trials are designed correctly, and if the drug can be made the same way every time.

Clinical trials are research studies involving volunteers that are designed to evaluate whether a new drug is safe, effective, and possibly better than the current (standard) treatment. There are usually three (sometimes four) consecutive phases of a clinical trial. Each successive phase involves a larger number of patients and provides more detail about the new drug's safety and effectiveness. Clinical trials frequently take years to complete and may involve thousands of patients.

Clinical trials follow a risk-based approach. Earlier phases focus on safety, dosing, and how the body processes the drug, while later phases focus on how well the drug works. Later phases include a larger group of clinical trial participants. Learn more about clinical trials.

Clinical review and FDA approval

If the clinical trials are successful, the drug sponsor submits a New Drug Application (NDA) to the FDA requesting approval of the drug for use by patients. The NDA contains results from the preclinical and clinical studies, details about how the drug will be manufactured, and specifics of how it will be labeled, which includes how the drug will be given (injection or pill, for example), the potential side effects, and any known interactions with food or other medications.

The FDA may approve the drug if the evidence shows it is effective and safe for use as described in the labeling. Although no drug is completely safe or free from side effects, a drug is considered to be safe if the benefits of taking it outweigh the possible risks.

Post-approval research and post-marketing surveillance

Once a drug receives FDA approval, it can be marketed and made available to doctors and patients. However, the FDA may require that the sponsor conduct additional clinical trials (phase IV trials) to look for other potential side effects; to study the drug in new patient groups, such as older adults; or to evaluate the drug's long-term effects. Some drug manufacturers may conduct their own phase IV trials or perform new research aimed at gaining FDA approval to use the drug in a new way, such as for a different type of cancer or a different population of patients.

The FDA also conducts ongoing safety monitoring of drugs currently on the market, and drug manufacturers are responsible for reporting any new or serious side effects to the FDA. The FDA may withdraw a drug from the market if new evidence from ongoing use indicates it is not effective as a treatment or it is not safe.

More Information

Drug Approval and Labeling

Podcast: What are Clinical Trials, with Richard Goldberg, MD

Video: Types of Cancer Clinical Trials, with Louis Weiner, MD

Video: Clinical Trials and Safety with Eric Singer, MD, MA

Patient Safety and Informed Consent

Additional Resource

FDA: Drug Development and Approval Process

Wednesday: Health Reform- Short comings Beware Caveat Emptor !

Thursday: The Future of Medicine

Friday:

Next week:  The Elephant in the Room

UNINSURED BALK AT OBAMACARE BITE

Half of ACA eligible adults still lack coverage due to cost.  Yes, and they will pay a penalty starting in 2015 for not being able to afford the  Affordable Care Act.

When it became obvious a couple of years ago that Obamacare would accelerate health care inflation, the law’s boosters began claiming that cost control was never its primary goal. PPACA’s promoters had previously promised that it would reduce annual health care expenses by $2,500 per family while improving access and quality of care. But the facts forced them to abandon that pledge and adopt a safer party line. As expressed by the New York Times, the new story goes thus: “At its most basic level, the Affordable Care Act was intended to reduce the number of Americans without health insurance.”

A new survey by the Kaiser Family Foundation may cause Obamacare partisans to regret retreating to that position. According to the KFF study, 53 percent of ACA eligible adults who remain uninsured cited cost as the main reason: “When asked why they lacked insurance coverage, more than half of adults who appear to be eligible for assistance volunteered that coverage was too expensive.” That’s right. A law that will cost $2 trillion over the next decade is unable to fulfill the one promise “reform’s” advocates still admit to making on its behalf. Obamacare’s last claim to legitimacy has vanished.

We are told by the President and his fourth estate flunkies that millions have enrolled via Obamacare’s exchanges and, presumably, at least a few have actually done so. But this administration’s habit of promulgating fraudulent enrollment figures makes it difficult to know how many legitimate sign-ups there have been. The folks at the Kaiser Family Foundation, on the other hand, have a good handle on how many failedto make the cut. And a lot of Americans lacked coverage when KFF finished its survey in December: “30 million people reported that they were uninsured as of the date of the interview.”

Adding insult to injury, millions of these people will be forced to pay fines for failing to buy health insurance coverage that Obamacare has rendered unaffordable. As theWall Street Journal explains, “About 2% to 4% of tax filers are expected to have to pay the fine for not having carried insurance in 2014, which is $95 per adult, or 1% of family income.” And the White House is getting nervous. Robert Pear writes in theNew York Times, “Obama administration officials… say they worry that the tax-filing season will generate new anger as uninsured consumers learn that they must pay tax penalties.”

Such is the genius of our Beltway masters. They pass a law that distorts the insurance market so badly that coverage becomes unaffordable, then fine people for failing to buy it. Next, of course, these brilliant statesmen will try to escape the consequences of their meddling by giving special dispensations to those whose lives they have disrupted. Robert Pear continues, “The White House has already granted some exemptions and is considering more to avoid a political firestorm.” The Obama administration is like a drunk driver offering money to someone he has sideswiped so she won’t telephone the police.

Meanwhile, beyond the walls of the Washington rehab ward, the Kaiser Foundation survey contains more bad news about the President’s “signature domestic achievement.” Contrary to the claims of Obama and his media mouthpieces, the fortunate few who can still afford coverage have continued to experience problems finding their way through the labyrinthine Obamacare sign-up process: “Nearly two-thirds of uninsured adults who sought ACA coverage said they had some difficulty with finding out how to apply, filling in the information, assembling the paperwork, or submitting the application.”

All of which suggests that those “news” reports in the legacy media about the rapidly declining uninsured rate should be taken with several metric tons of salt. The Kaiser survey certainly confirms the wisdom of such skepticism. In fact, no less than 20 percent of the uninsured individuals interviewed by KFF lost their insurance after the implementation of Obamacare: “[O]ne in five uninsured adults actually lost coverage in 2014.” Perhaps this is why public opinion surveys have consistently shown that the vast majority of uninsured Americans view the “Affordable Care Act” with a jaundiced eye.

Three Recommendations for President Obama’s Precision Medicine Initiative

Attribution:  Spencer Nam

One of the pleasantly surprising announcements President Obama made during his 2015 State of the Union address was “a new Precision Medicine Initiative to bring us closer to curing diseases like cancer and diabetes.” 



Although the term ‘Personalized Medicine’ is also used to convey this meaning, that term is sometimes misinterpreted as implying that unique treatments can be designed for each individual.^[1]

Given precision medicine’s potential to solve many outstanding health care issues and lower costs without compromising clinical quality and performance, the President’s proposal is a welcome initiative. Many of the challenges we face practicing symptom-focused intuitive medicine could be overcome by turning toward precision medicine, a process of precisely diagnosing and targeting disease.

However, announcing the initiative is one thing. As with all policy discussions, the devil is in the details – and there are three details specifically that could make the difference between political rhetoric and a policy that truly improves the health of American citizens.

1.  Focus on the entire process of the disease – starting with prevention. Because most chronic diseases show few symptoms until the disease has significantly progressed, treatments for cancer and diabetes patients are primarily at the disease management phase. However, we are acutely aware that the best way to “cure” cancer or diabetes is prevention, and prevention requires better early diagnosis. Unfortunately, we still lack convenient and accurate ways to diagnose for various cancers and diabetes. Given the high costs of treating advanced-stage chronic diseases, precision diagnosis of risk factors or disease progression will materially lower the costs of health care.

For example, currently the only place we can check hemoglobin A1c (HbA1c), or blood glucose levels, is at physicians’ offices. With nearly 30 million Americans with type-2 diabetes and another 30 million pre-diabetic, it is time to develop a more convenient and affordable way to check for HbA1c so more regular testing can be done, particularly for those with risk factors. Cancer diagnostics is also confusing and difficult, with imaging modalities (CT, PET, MRI, X-ray) as the only reliable diagnostics methods. We need to develop more reliable and accepted diagnostics to identify and monitor cancers in their early stages.

2.    Strategically target diseases. Particularly in cancer and type-2 diabetes, two of the fastest growing disease segments in the United States, there is a significant opportunity for precision medicine to improve early diagnosis and treatment, and lower the costs of care. Remember, we tackled HIV and AIDS issues over the past thirty years with a precise target (HIV) and with research focused on quickly translating basic science to clinically effective and safe drugs. Because cancer and diabetes are systemic diseases, affecting multiple aspects of a human body, focusing on translational science based on specific types of cancer or specific aspects of diabetes may in fact accelerate not only the understanding of the diseases but also improve the treatment methods at each stage.

While our understanding of cancer and diabetes has substantially grown over recent decades, we’ve also found the core issues of these diseases to be much more complex and involved than previously understood. As PresidentKennedy set a national goal of “landing a man on the moon and returning him safely to the earth,” by setting their sights on one or two of the nation’s most critical diseases, President Obama and his team of experts could provide a strategic framework for marshalling resources to make real progress toward their cure.

3.      Set standard definitions and metrics. One of the major challenges in migrating toward precision medicine is lack of a common clinical language and metrics that help us to refine our interpretations and focus our messages to physicians and patients. Because cancer and diabetes are still treated in the realm of intuitive medicine, different physicians can provide different opinions on these diseases. Although we need to appreciate individuals’ genetic and biological uniqueness in discussing chronic diseases, precision medicine cannot establish deep roots without more commonly accepted definitions and associated metrics.  

Gaining more precise understanding of cancer and diabetes and developing precise diagnostics and treatments to be administered at the right time will reduce inefficiency and waste –delivering substantial dividends. However, let’s not forget that a detailed education plan as well as appropriate reimbursement schedule will be integral for the initiative to truly go beyond the drawing board. By providing strategic focus and direction to lead the Precision Medicine Initiative forward,President Obama has an opportunity make a real impact.

Often, though not necessarily, PM involves the application of panomic analysis and systems biology to analyze the cause of an individual patient's disease at the molecular level and then to utilize targeted treatments (possibly in combination) to address that individual patient's disease process. The patient's response is then tracked as closely as possible, often using surrogate measures such as tumor load (v. true outcomes, such as 5 year survival rate), and the treatment finely adapted to the patient's response.^[2] The branch of precision medicine that addresses cancer is referred to as "precision oncology".^[3]

Inter-personal difference of molecular pathology is diverse, so as inter-personal difference in the exposome, which influence disease processes through the interactome within the tissue microenvironment, differentially from person to person. As the theoretical basis of precision medicine, the "unique disease principle"^[4] emerged to embrace the ubiquitous phenomenon ofheterogeneity of disease etiology and pathogenesis. The unique disease principle was first described in neoplastic diseases as the unique tumor principle.^[5] As the exposome is a common concept of epidemiology, precision medicine is intertwined with molecular pathological epidemiology (MPE). MPE research is capable of identifying potential biomarkers for precision medicine.^[6]

Precision Medicine is and will be in a state of evolution as markers are defined and testing becomes cost-effective. Moving Precision Medicine into the clinic, from research will usher in a new age of medicine.

Spencer Nam is a senior research fellow at the Clayton Christensen Institute for Disruptive Innovation, where his work focuses on disruptive innovations in the health care industry.

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