Archive for the ‘Diagnostics’ Category

2014: The Year of the Patient

December 17, 2014

As we reach the end of another year, we once again look back at recent advancements and milestones in the field of personalized medicine. As we celebrated 10 years of progress, we also looked toward the future, identifying changes needed to ensure another decade of discovery. Reflecting upon the highlights of 2014, it is clear that this truly was the year of the patient. A renewed sense of urgency to shift towards a more patient-centered approach to care has been created across the healthcare system.

The following captures highlights from The Age of Personalized Medicine Blog for 2014.

Michael Kolodziej, M.D., National Medical Director for Oncology, Office of the Chief Medical Officer, Aetna, kicked off the year with reflections on the challenges facing the adoption of personalized medicine.

So what are the practical challenges? There are many. And many share the underlying theme that the old paradigms do not work so well. … Perhaps the biggest challenges lie in the area of clinical utility, which impacts providers, payers and regulatory agencies. Patients are impacted in a huge way. Most people have an idea of where we need to go, but we have a shortage of ideas about how to get there. Finally, all of this occurs in the setting of unsustainable growth in health care spending, and the near uniform agreement that we need to spend our money in a more intelligent, impactful way. … We have a lot of work to do together.

In March, we were honored to share the personal and candid story of Stephanie Dunn Haney, a lung cancer survivor, and her experience with molecular testing and targeted therapies. Stephanie’s story continues to remind us of the hope personalized medicine offers to so many.

Molecular testing and personalized medicine gave me my life back, and my sense of a future back. While I’m realistic enough to know that my daughters are fairly certain to lose their mother before they are grown, I also know I have tools to fight with, and a responsibility to share my story.

As we talk about the need to keep the patient at the center of all that we do, we at the Personalized Medicine Coalition (PMC) saw a need to establish a baseline of consumer awareness, knowledge and attitudes about personalized medicine. In July, PMC released a national survey, U.S. Public Opinion About Personalized Medicine, with key findings that will guide future outreach and education efforts.

We’re at the beginning of the golden age of personalized medicine. Armed now with a clear picture of the public’s opinion, we have an opportunity to raise awareness and increase understanding of what personalized medicine is, and how it can transform approaches to healthcare delivery.

Of course, in order to bring molecular tests and targeted therapies to patients, key regulatory and reimbursement areas must be addressed. PMC also published The Future of Coverage and Payment for Personalized Medicine Diagnostics in Julywhich took a critical look at CMS policies, highlighting specific challenges to the further implementation of personalized medicine diagnostics.  Later that month, the U.S. Food and Drug Administration’s (FDA) released its long-awaited final guidance on the regulation of companion diagnostic devices, as well as proposed framework for regulating laboratory developed tests (LDTs).

Investors have long argued that clarity is necessary in both regulation and reimbursement for continued advancement of personalized medicine. We now have clarity on FDA’s current thinking although many issues remain unresolved. The community has time to consider this framework and may soon have a chance to provide public comments. And finally, the pharmaceutical industry has the FDA’s assurance that targeted treatments will not be held up by co-development challenges.

In October 2014, the PMC, the American Association for Cancer Research (AACR), and Feinstein Kean Healthcare (FKH) convened the second national Turning the Tide Against Cancer national conference, which brought together leaders throughout the healthcare and policy communities for a passionate and engaging discussion on the importance of moving towards a more high-value, patient-centric system of cancer care.

Keynote speaker, cancer survivor, and The New York Times Emmy® Award winning columnist of “Life, Interrupted,” Suleika Jaouad, shared insights into communication challenges patients face during a Q&A session. Suleika’s words serve as a reminder that if we are to increase adoption of personalized healthcare, we must ensure patients are given the tools and education needed to properly understand their treatment options.

Communication is the golden ticket. We live in the WebMD age where patients often consult Google before they consult a doctor. This can be dangerous and can lead to misinformation and misunderstandings. Creating an environment where the patient feels comfortable asking questions and talking to their medical team is crucial.

Following the conference, FKH Chairman, Marcia A. Kean, M.B.A., proposed next steps:

I propose that every individual touched by cancer, and every organization concerned about the nation’s cancer burden, take responsibility for three actions.

  1. Review the Issue Brief, and share your thoughts/ideas about the policy options and/or propose other options
    .
  2. Involve your organization in the Turning the Tide Against Cancer Through Sustained Medical Innovation initiative, by participating in our activities and events.

  3. Join our partners PMC and AACR and advocate for those options that you agree with, integrating them into your own policy platforms and your communications with policymakers in order to drive momentum and catalyze change.

We encourage you to learn more about the Turning the Tide Against Cancer initiative, and the important work we are doing to make a difference for cancer patients.

As an appropriate end to the year, we celebrated the 10th Anniversary Personalized Medicine Conference in November, and conference organizer Raju Kucherlapati, Ph.D., Paul C. Cabot Professor of Genetics, Harvard Medical School, reflected on a decade of developments in personalized medicine.

The past decade has witnessed many exciting new developments in personalized medicine: the significant reduction in the cost of DNA sequencing and related technologies; the use of these technologies for an unprecedented rate of discovery of human disease genes; a near universal acceptance of the importance of genetics and genomics in drug development, especially for cancer; the levels of investment in personalized medicine companies; recognition of the importance of personalized medicine by professional societies; and the deep involvement by the administrative and legislative bodies in the U.S. and throughout the world.

2014 was a milestone year. We look forward to the year ahead, and the continued opportunity to engage with leaders throughout the personalized medicine community, and across the healthcare system, to discuss the future of personalized healthcare and how we can provide the best value to patients.

No Test, No Drug

November 4, 2014

It is very difficult to select the appropriate therapy for a patient if you don’t know what disease you are treating. For the practicing physician, the patient’s presenting symptoms, history, physical examination, and radiological and biochemical evaluations typically establish the diagnosis by placing the disease in one of many accepted clinical diagnostic categories (phenotypes). The search for more clearly recognizable, homogeneous patient phenotypes has driven much of our early medical progress. Treating congestive heart failure, for example, is much more productive than trying to treat dropsy; a much older and imprecise collection of not-otherwise-specified edematous conditions.

Have we now arrived at the limit of utility of the descriptive phenotypic disease classification? I suggest that genotypic descriptions based on the root cause, or key molecular attribute, of the disease will rapidly replace phenotype-based disease classifications.  This can’t happen fast enough for those in drug discovery where a drug’s mechanism of action (increasingly derived from genetic considerations) must be matched with a recognized clinical indication.

The transition from phenotype-based to genotype-based indications will not be easy. It was not that long ago that we recognized that several distinctly different genetic alterations can lead to the same clinical phenotype. For example, patients with the same clinical presentation of cystic fibrosis are not expected to respond to a therapy such ivacaftor (Kalydeco, Vertex Pharmaceuticals) unless they have the appropriate CFTR mutations among the many CFTR mutations that cause cystic fibrosis.

We have discovered that patients with the same molecular basis of disease may have distinctly different phenotypes. This means that two patients with markedly different clinical presentations may be responsive to the same therapy specifically directed at their shared molecular basis of disease. While this has yet to be reduced to routine practice, recent discoveries are clearly taking us in this direction.

For example, Kevin Strauss and colleagues at the Clinic for Special Children (Human Molecular Genetics, July 2014) have identified a variant of KCNH7 (which encodes a potentially targetable ion channel) that strongly associates with bi-polar spectrum disorder. Especially noteworthy is their observation that patients with the KCNH7 variant do not present as a single psychiatric phenotype but rather with a variety of axis 1 major affective disorders.

But medical progress in this new era depends upon coordinated activity by multiple stakeholders. In this instance, psychiatrists must be comfortable with genetic classifications of disease and be sufficiently knowledgeable to order the correct drug for patients with similar phenotypes but differing genotypes. The drug developer must have established the safety and efficacy of a new drug in patients with the specific genetic alteration and also potentially have established the lack of efficacy in patients with similar phenotypes but lacking the genotype for which the drug was developed. A diagnostic company must have developed and validated a FDA approved genetic test. Finally, there must be a reimbursement scheme that recognizes the contributions of all of the above parties.

For this to become commonplace, the clinical molecular test (at least in a prototype form) will need to exist once one begins to look for the new chemical entity that will become a drug. This will also mean that we need to invest more in genetic epidemiology. The availability of the drug for the target and the test for the target will be essential in early development, especially if there is a plan to enrich for patients with appropriate particular genotype among those with a similar phenotype.

Does this mean that all new drugs in development need a companion diagnostic? Not just yet, though we may be getting there. There is plenty of disease biology for which a drug can be made but for which a test can’t be found, including in the field of immunotherapy. But even here the secrets that regulate immune response will be revealed and genotype testing will be a prerequisite for prescription writing in this field and in almost all indications.

These and other topics will be explored at the Harvard Personalized Medicine Conference in Boston on November 12-13.


The Personalized Medicine Conference is an annual two-day event co-hosted and presented by Partners HealthCare Personalized Medicine, Harvard Business School, and Harvard Medical School in association with the American Association for Cancer Research and Personalized Medicine Coalition.

For more information and to register for the 10th Annual Personalized Medicine Conference, please visit http://www.personalizedmedicineconference.org.

Required Reading: September 2014

September 26, 2014

Great stories are published daily about the impact personalized medicine is having on individual patients, and the medical community as a whole, but it can be a challenge to stay on top of the news. With that in mind, we bring to you a monthly roundup of the three to five most thought-provoking articles we are reading, sharing and discussing with our colleagues.

This is the September 2014 installment of Required Reading.


Medical Calculators Use Big Data to Help Patients Make Choices by Laura Landro, The Wall Street Journal

Michael Kattan, chairman of the department of quantitative health sciences at Cleveland Clinic’s Lerner Research Institute, discusses sophisticated risk calculators, or “nomograms,” that can combine a patient’s unique characteristics, such as age, gender, race, extent and type of disease and other health factors; compare them with the vast databases of similar cases and studies; and use them to predict probable outcomes depending on the treatment a patient chooses.

FDA’s Shuren Defends Plan to Issue Guidance for LDTs at House Hearing by Michael D. Williamson, Bloomberg BNA

On September 9, the House Energy and Commerce Committee’s Subcommittee on Health held a hearing to examine the regulation of laboratory developed tests (LDTs) as a continuation of the committee’s 21st Century Cures initiative. Members heard testimonies from various witnesses on recently released guidance from the U.S. Food and Drug Administration (FDA) and its impact on innovation and the practice of precision medicine. Read more about the FDA’s proposed framework for regulating LDTs.

Experts Warn US in Danger of Losing Biotechnology Edge by Chris Casey, Medical Xpress

The United States is in potential danger of losing its biomedical edge to countries that are aggressively funding research into personalized medicine, according to discussion that emerged at the 21st Century Cures Roundtable on September 5. Roundtable panelists noted that biotechnology is at a crossroads in America, and that funding levels for research have flattened in recent years.

Researcher Urges Wider Genetic Screening for Breast Cancer by Rob Stein, NPR Shots Blog

Mary-Claire King, the geneticist who identified the first breast cancer gene, is recommending that all women get tested for genetic mutations that can cause breast cancer, regardless of their personal or family history. According to a paper she recently published in Proceedings of the National Academy of Science, women who carry mutations in BRCA1 or BRCA2, but have no family history of breast or ovarian cancer, have the same high risks of developing either cancer as those who are identified to be at-risk by virtue of their family history.

Survey Reveals Insights About Awareness, Understanding of Personalized Medicine, Part 2

September 16, 2014

Following the launch of the Personalized Medicine Coalition’s U.S. Public Opinion About Personalized Medicine survey results, the Pharmaceutical Research and Manufacturers of America’s (PhRMA) asked the panelists from our launch event at the National Press Club – What key benefits of personalized medicine do you think the public needs to know about in order to embrace this approach to health care?

The survey, conducted by KRC Research, tells us that most Americans do not know what personalized medicine is, but once the concept is explained to them they are very supportive of advancing the field. In these short video interviews, each of these experts weighs in on how we connect the dots from lack of knowledge to wide support for personalized medicine.

The full set of video responses can be viewed on PhRMA’s Conversations blog, with additional commentary from Raju Kucherlapati, M.D., Professor, Department of Genetics at Harvard Medical School and Mark Richards, Senior Vice President, Management Supervisor at KRC Research.

Amy M. Miller, Ph.D., Executive Vice President, Personalized Medicine Coalition, discusses how personalized medicine is changing the way we experience health care today, including the development of the first cystic fibrosis treatment in over 20 years and other medicines that are improving patients’ quality of life.

Donna R. Cryer, J.D., President and CEO, Global Liver Institute, talks about the importance of educating both patients and clinicians about personalized medicine and its potential benefit, as well as her personal experience as a patient who has benefited from targeted treatments.

Randy Burkholder, Vice President, Policy, PhRMA, highlights the important future of personalized medicine and the commitment of America’s biopharmaceutical research companies to advancing the field and the science of personalized medicine.

Learn more about U.S. Public Opinion About Personalized Medicine and review the survey findings by reading Part 1 of our series or visiting the PMC website.

Required Reading: August 2014

August 28, 2014

Great stories are published daily about the impact personalized medicine is having on individual patients, and the medical community as a whole, but it can be a challenge to stay on top of the news. With that in mind, we bring to you a monthly roundup of the three to five most thought-provoking articles we are reading, sharing and discussing with our colleagues.

This is the August 2014 installment of Required Reading.


The Price of Personalization by Timothy Gower, Proto Magazine

This article explores the growing debate over the cost and value of personalized medicines and identifies ways that the healthcare system may need to adapt to accommodate the development and use of increasingly more targeted therapies that work for smaller patient populations.

FDA to Regulate Thousands Of Cancer, Genetic, and Other Diagnostics by Matthew Herper, Forbes

Earlier this month, the U.S. Food and Drug Administration (FDA) announced plans to regulate laboratory developed tests, many of which are diagnostics developed as result of the exploding field of genetics. The new regulatory framework proposes that any test used to diagnose a disease or to decide on a course of treatment will need to be cleared by FDA before it can be utilized.

It’s Time for Us to Think About Cancer Differently by Paul Mejia, Newsweek

A recent genomic study published in the journal Cell suggests that 1 in 10 cancer patients could be more accurately diagnosed if cancer were defined by molecular and genetic characteristics, rather than by where it is located. Researchers believe that reclassifying cancer by identifying the type of cell that caused the disease, instead of the tissue type, could ultimately lead to better treatment in the future.

RNA Combination Therapy for Lung Cancer Offers Promise for Personalized Medicine by Kevin Leonardi, MIT News

Early research at the Koch Institute for Integrative Cancer Research at MIT offers promise for personalized cancer treatments using RNA combination therapies to improve therapeutic response. The development of an efficient delivery system of individual or combined small RNAs to solid tumors could help regulate genetic mutations underlying a given patient’s cancer.

Survey Reveals Insights About Awareness, Understanding of Personalized Medicine, Part 1

August 22, 2014

Earlier this year, the Personalized Medicine Coalition (PMC) commissioned U.S. Public Opinion About Personalized Medicine, a nationally representative survey of 1,024 adults gauging consumer awareness, knowledge and attitudes about personalized medicine.

The key findings of the survey were positive. Although less than 4 in 10 Americans had heard of it prior to being surveyed, respondents are interested in learning more about personalized medicine and are supportive of the concept. For those who had heard of personalized medicine, their knowledge was shallow and did not associate the term with diagnostic testing or targeted treatments. This highlights the need for education to a willing public.

When the surveyed individuals were given a definition of personalized medicine, approximately two-thirds were receptive and expressed positive opinions about its prospects.

Respondents easily pointed out the major benefits of personalized medicine, noting that it could give them more knowledge to prevent or treat their illness, help them choose the most effective treatments with their doctors, and lead to a decline in unnecessary treatments, side effects, invasive procedures and trial and error medicine.

Many of the individuals who were surveyed even raised questions, specifically regarding the efficacy, potential risks, cost, access and affordability. A majority agreed that insurance should cover personalized medicine if it is recommended by a doctor.

We’re at the beginning of the golden age of personalized medicine. Armed now with a clear picture of the public’s opinion, we have an opportunity to raise awareness and increase understanding of what personalized medicine is, and how it can transform approaches to healthcare delivery.

Stay tuned for part two of this blog post series as we hear from leading experts, and the researcher who conducted the survey, on what key benefits of personalized medicine they think the public needs to know about in order to embrace this approach to healthcare.

In the meantime, learn more about U.S. Public Opinion About Personalized Medicine and review the survey findings by viewing the slideshow below or visiting the PMC website.

FDA Outlines Personalized Medicine Policy with Publication of LDT Draft Guidance Document, Final Guidance on Companion Diagnostics

August 15, 2014

On July 31, FDA announced drastic changes to regulation for personalized medicine products and services when it coupled the release of the long-awaited final guidance document on the regulation of companion diagnostic devices with a proposed framework for regulating laboratory developed tests (LDTs), which was also long-awaited or long-feared, depending on your perspective.

The final guidance on In Vitro Companion Diagnostic Devices was welcomed by the personalized medicine community because in the document, FDA clarified the path for co-developed drug-diagnostic products, and finalized their assertion that new targeted therapeutics will not be kept from the market if the diagnostic kit is not ready at the same time. This enables promising new drugs to come to market while also allowing the laboratory community to fill testing needs in cases where an FDA-approved kit is not available for therapeutic selection, dosing and avoidance decisions.

However, many issues remain to be addressed.

To address concerns that FDA regulation will pose obstacles to an already challenged laboratory industry, there is a rather long transition phase — nine years — and an initial focus on high-risk. FDA defines high-risk LDTs as those with the same intended use as cleared or approved companion diagnostics, LDTs with the same intended use as an FDA-approved Class III medical device, and certain LDTs for determining the safety and efficacy of blood or blood products. This focus and transition period will allow clinical laboratories and FDA time to adjust. By focusing initial regulation on high-risk LDTs, FDA makes a strong argument for the framework, and slices off a rather small segment of the LDT market.

Many have argued that FDA does not have the bandwidth to regulate LDTs. FDA responded to this claim by reiterating enforcement discretion for the vast majority of LDTs and outlining a process for LDT regulation, which might be less onerous than traditional regulatory pathways for medical devices.

Although FDA made great efforts to address concerns about the Agency’s new regulatory enforcement, it did not address perceived conflicts between laboratory regulation under Clinical Laboratory Improvement Amendments (CLIA) and this new framework. Furthermore, FDA intends to use an expert advisory panel to provide recommendations to the Agency on LDTs risks and classification on certain categories of LDTs, as appropriate. I suspect that defining those categories will be contentious and, at times, difficult.

Investors have long argued that clarity is necessary in both regulation and reimbursement for continued advancement of personalized medicine. We now have clarity on FDA’s current thinking although many issues remain unresolved. The community has time to consider this framework and may soon have a chance to provide public comments. And finally, the pharmaceutical industry has the FDA’s assurance that targeted treatments will not be held up by co-development challenges.

BREAKING NEWS: FDA Notifies Congress of its Intent to Publish Framework for Regulatory Oversight of Laboratory Developed Tests (LDTs)

July 31, 2014

Summers in D.C. are notoriously slow. FDA, however, has added excitement to this summer by informing Congress of its intent to publish a long-awaited framework for LDT regulation.

In its notice to Congress, FDA included what appears to be a draft of the document. After the mandatory 60-day Congressional review, the draft guidance document will be formally issued for public comment.

Within the draft framework, FDA proposes a risk-based, phased system of oversight. They recognize community concerns around access and do not intend to interrupt the marketing and sale of currently available tests. Furthermore, FDA expresses the intent to continue using enforcement discretion for forensic and organ transplantation uses, traditional LDTs, and LDTs for unmet needs.

The document outlines the history of LDT regulation, FDA’s policy of enforcement discretion, and how personalized medicine has caused FDA to reconsider that policy.

We will continue to provide updates on the development of framework for regulatory oversight of LDTs, with additional in-depth commentary next week on this issue and the related news of FDA’s final guidance on companion diagnostics.

For additional information on the current regulation of LDTs, please read PMC’s report “Pathways for Oversight of Diagnostics.”

Key SGR Fix Brings Relief to Diagnostics Industry

April 8, 2014

On April 1, the diagnostics industry let out a collective sigh of relief as President Obama signed into law HR 4302. Officially known as the Protecting Access to Medicare Act of 2014, many refer to the law as “Doc Fix” or “SGR fix”, focusing on the delay, yet again, of the 24 percent physician pay cut as a part of Medicare’s sustainable growth rate (SGR) formula.

However, my attention, along with that of the diagnostics industry, focused on the provisions in the law that protect clinical diagnostics from unpredictable repricing (subscription required) under the Centers for Medicare and Medicaid Services (CMS) Clinical Lab Fee Schedule (CLFS).

The passage of this law showcases the need and value of the industry to unite in highlighting policies that, though unintended, challenge innovators by creating an uncertain reimbursement environment. Predictable reimbursement policies encourage exploration and innovation within the diagnostics community, improving health care through advances in diagnosis and beyond.

This law acknowledges the transformative scientific advancements the industry has achieved in recent years, catching our policies up with our technologies.

Many questions remain as we look at the implementation of this law, and as such we remain committed to convening the personalized medicine community to work in collaboration with CMS.

New Approaches for Practical Challenges in Personalized Medicine

January 27, 2014

When I received the invitation to speak at the Personalized Medicine World Conference (PWMC), I was excited. When I saw the program and faculty, I was honored. When I received my “assignment,” I was intimidated. To share the podium with many of the luminaries in the field of genomics — even to hear them speak — is tremendously exciting. In contrast, how can they really be interested in hearing me speak on the real-world challenges providers and payers face in bringing genomics advances from bench to bedside more quickly?  I cannot answer this question. Although based solely on the number of conferences to which I am invited on this topic, someone must care. They should. Making the science “work” is only the first step in moving from bench to bedside.

As I was preparing my talk, I reflected on the story Sid Mukherjee, M.D., Ph.D., tells in his fabulous book, The Emperor of All Maladies: A Biography of Cancer. I’m not usually a big non-fiction fan, but if you are involved in cancer care in any way, this is a must read. Perhaps the book resonated because my professional career spanned many of the seminal events described in the book. That, and I share Dr. Mukherjee’s general perspective on the challenges of making meaningful advances in cancer treatment. The bottom line: cancer is tough. Just when we think we’ve made some great progress, it teaches us humility. Still, it is impossible not to be excited and enthusiastic about how far we have come in our understanding of the genetics of cancer. I really think we are experiencing a sea change. We must begin to think about navigating these changing currents in the world of health care reform in order to take best advantage of that progress.

So what are the practical challenges? There are many. And many share the underlying theme that the old paradigms do not work so well. Traditional methods of quality control in test performance, i.e. analytical validity, are a big problem. Proficiency testing and standards do not currently exist. To be honest, most doctors do not think about them when ordering a test. The billing and coding of molecular tests have been undergoing dramatic evolution but is still not suited to multi-analyte assays. Perhaps the biggest challenges lie in the area of clinical utility, which impacts providers, payers and regulatory agencies. Patients are impacted in a huge way. Most people have an idea of where we need to go, but we have a shortage of ideas about how to get there. Finally, all of this occurs in the setting of unsustainable growth in health care spending, and the near uniform agreement that we need to spend our money in a more intelligent, impactful way.

We have a lot of work to do together. It is important to remember we are all on the same side. We have a chance to make a huge difference, but we need to do it right.

What do you think our greatest challenges and opportunities are today? I look forward to the discussion in California.

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Read additional posts from speakers and participants of the 6th Annual Personalized Medicine World Conference on January 27-28, 2014. For more information and the full agenda, visit: 2014sv.pmwcintl.com.


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