Required Reading: September 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.

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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.

Required Reading: August 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.

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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.

FDA Outlines Personalized Medicine Policy with Publication of LDT Draft Guidance Document, Final Guidance on Companion Diagnostics

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)

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.”