Call to Action: Proposed FDA Regulations Could Limit Cancer Patient Access to Life-Saving Therapies

This article first appeared on my February 1, 2015, blog for Cure Today Magazine.  Reprinted here with permission.

As posted in a recent CURE article, the US Food and Drug Administration (FDA) has proposed draft regulations titled “Framework for Regulatory Oversight of Laboratory Developed Tests (LDTs).”  The FDA should withdraw this proposed framework because it could limit cancer patient access to potentially life-saving therapies.

Metastatic cancer patients have waited years for the hope that targeted therapies and genomic testing are now giving us. Don’t let the FDA throttle our hope. Knowledge of cancer genomics and proteins is evolving faster than government regulation can move.

Of course, we all want LDTs to be as validated, accurate and clinically relevant as possible. However, we also want the laboratories where these clinical testing services are performed to be able to exercise the flexibility, innovation and medical judgment necessary for good outcomes in thousands of cancer patients.  This isn’t possible with the proposed FDA regulations.

Please sign the petition at, and ask your friends and family to sign. If you or a loved one has benefited from molecular or genomic testing, please say so in the comments.  The petition and its comments will be submitted to the FDA as an official comment. The more signatures we have, the stronger our voice will be.

Here is a specific example of patient harm these proposed regulations might cause, taken from my own journey with metastatic ROS1-positive non-small lung cancer (NSCLC).

I live near Seattle. Because I was able to send my slides to University of Colorado for ROS1 testing, and my slides tested positive for ROS1, I was able to take crizotinib and achieve two years (and counting) of No Evidence of Disease. LDTs for ROS1 have been validated by medical research and have given many patients months or years of extra time.

Under the proposed regulations, some patients might have to travel to a distant or out-of-network medical facility to get the existing ROS1 test and receive treatment for their ROS1 cancer. In addition, some labs might stop offering the test because of the lengthy and cost-prohibitive process to obtain FDA approval. A medically validated test that is currently saving lives may become inaccessible to future lung cancer patients. The proposed FDA regulations would have effectively interfered with the practice of medicine.

Getting the best diagnostic and treatment outcomes from available cancer specimens relies of the practice of medicine, particularly the judgment and skill of pathologists, molecular pathologists and other molecular laboratory professionals.  The use and safety of LDTs can’t be regulated in the same manner as self-contained medical devices such as stents, or commercial test kits that come with pre-defined instructions.  Yet that is how the proposed regulations treat LDTs.

All cancer patients should have access to clinically validated tests that can help decide the best course of treatment.  Please sign the petition to tell the FDA to withdraw its proposed regulations.


A more detailed version of my ROS1 example:

ROS1-rearranged non-small cell lung cancer (NSCLC) testing and treatment with crizotinib are recommended in National Comprehensive Cancer Network guidelines because crizotinib, an FDA-approved drug for ALK-positive NSCLC, “showed marked antitumor activity” against ROS1 NSCLC, with a 72 percent  response rate in clinical trials—one of the highest response rates of any lung cancer drug—and a duration of response that exceeds 17.6 months.  Crizotinib is currently available off-label for ROS1 NSCLC through most insurance companies because of its strong clinical evidence of effectiveness.  Since most cancer treatment facilities do not offer an LDT for ROS1, they send slides to one of several CLIA-approved laboratories for testing, and treat ROS1-positive patients at home with crizotinib. Because no FDA-approved companion test exists for ROS1, any non-FDA approved LDT used to detect the ROS1 rearrangement would fall under the “LDT for Unmet Needs” exemption — IF the LDT is ONLY used for patients within the laboratory’s healthcare system. Therefore, any lung cancer patient whose home clinic does not offer ROS1 testing would have to either send specimens to a laboratory with an FDA-approved ROS1 LDT (none are available at present), or travel for diagnosis and treatment to a facility that offers a ROS1 LDT within its healthcare system–even if the patient’s insurance doesn’t cover that system.  Many patients may not be able to travel to another healthcare facility for ROS1 testing and treatment because they might be too sick, or face work, family, or financial constraints (insurance doesn’t cover travel expenses).  Thus, under the proposed regulations, some future ROS1 patients would not be able to get crizotinib treatment, even though that treatment is available today at their home cancer clinic.

Another example from lung cancer:

Under the proposed regulations, when using an FDA-approved companion test kit (currently available for EGFR and ALK NSCLC), any change in equipment, reagents, or patient specimen type must be submitted to the FDA and obtain the FDA’s approval before it can be offered to patients. Currently patients who have little tumor tissue (a common problem in lung cancer) can sometimes be tested for ALK based on cells obtained from pleural fluid or lymph nodes. Under the proposed regulations, only tumor tissue could be tested for ALK (that’s what the FDA-approved test kit requires) unless laboratories submit their modified ALK LDT for FDA approval. Also, published medical research has demonstrated that sometimes patients test negative for ALK using the FDA-approved test, but those patients may test positive using alternative, validated testing methods (such as genomic sequencing) and respond well to crizotinib. Under the new regulations, those alternative testing methods won’t be allowed unless they obtain FDA approval.  Lung cancer patients who don’t have enough tumor tissue would either go without testing, or undergo risky biopsies in hopes of obtaining enough tumor tissue.

Image credit:  “Researcher looks through microscope (2)” by Rhoda Baer. Licensed under Public Domain via Wikimedia Commons.

#LCSM Chat Topic 1/15 at 8PM ET: “Should the FDA Regulate Which Cancer Tests You Can Have?”

The US Food and Drug Administration (FDA) announced its intention to regulate laboratory developed tests.  Under the FDA’s proposed Framework for Regulatory Oversight of Laboratory Developed Tests (LDTs) — which treats LDTs as medical devices and healthcare providers as manufacturers — laboratories would have to submit applications for expensive premarket review for thousands of LDTs if they wish to continue offering them to patients.  This could limit access to life-saving genomic testing for patients who have cancer and other conditions treatable with targeted drugs.

This Thursday, January 15, 2015, at 8 PM Eastern, the subject for #LCSM Chat will be “Should the FDA regulate which cancer tests you can have?”  We invite patients, caregivers, doctors, researchers, professional societies, advocates, and regulators in all cancer communities to participate in this discussion.  Your moderator will be Janet Freeman-Daily.

Our discussion topics:

  • T1: What info about an LDT would give you confidence that it accurately identifies cancer or treatable mutations?
  • T2: Does FDA approval ensure accuracy and usefulness of LDTs? What other info/oversight could do this?
  • T3: Would FDA regulation of LDTs interfere with the practice of medicine?
  • T4: Should only FDA-approved LDTs be used to guide treatment of cancer patients?  Why or why not?

Background information about subject is below.

We look forward to seeing you Thursday 1/15 at 8 PM.  Please be sure to include #LCSM in your tweets to participate in the chat.  For more about how to participate, see our #LCSM Chat Primer.



Laboratory developed tests (LDTs) are developed, validated, performed and interpreted by trained professionals in hospital, academic, and commercial laboratories.  Examples of important LDTs for lung cancer patients include blood tests (blood count, liver function, cancer biomarkers), identification of biopsied cell types (e.g., adenocarcinoma, small cell lung cancer), molecular tests (EGFR, ALK, ROS1), and genomic panels (which can test for over 200 cancer-causing gene mutations and rearrangements from one set of tissue samples).  While some tests are automated, the results of these tests often depend on the judgment and skills of medical professionals such as MD pathologists or PhD scientists.  Cancer-related LDTs are often developed at the request of (and in consultation with) oncologists to allow physicians to tailor treatments for their patients.

LDTs that are performed in your hospital’s lab or commercial labs (like Foundation Medicine) typically are not regulated by the FDA.  However, labs are regulated and certified by the Centers for Medicare and Medicaid Services through Clinical Laboratory Improvement Amendments (CLIA), state health agencies, and organizations such as the College of American Pathologists.  They also participate in programs such as proficiency testing to ensure accuracy.

Unlike LDTs, tests that are boxed and shipped to other labs and professionals contain all of the components and information necessary to perform the test outside of the laboratory in which it was designed and manufactured.  Because they are manufactured by a company and not developed and validated by health professionals as part of a medical service, test kits are regulated by the FDA. The BRAF test manufactured by Roche is an example of an FDA-regulated kit.

Under the proposed framework for regulation of LDTs, the FDA would regulate LDTs just as they would medical devices such as stents, blood glucose monitors or hip replacements.  Regulations would vary depending on risk categories, with tests that determine patient treatments considered as “high risk.”  If this proposal were finalized, in many cases laboratories would have to pull their LDTs from their list of patient services or submit them for review by the FDA.

At first glance, FDA regulation of LDTs might seem like a good idea.  The number of commercially available LDTs to detect mutations in cancer tissue has exploded from a handful in 2011 to dozens today.  Some people argue we need regulations to protect vulnerable patients, citing as one example the Ovasure LDT for early detection of ovarian cancer, which the FDA forced off the market in 2008.  The test aimed to detect specific proteins in the blood that, when analyzed via a mathematical algorithm, could determine whether the patient had ovarian cancer.  However, the LDT was marketed before its accuracy was validated in a large group of patients.  As a result, Ovasure false positives caused some women to have their ovaries removed when they did not actually have ovarian cancer.  We need to prevent such things from happening, right?

Yes, we want LDTs to be as accurate and clinically useful as possible.  But FDA regulation will not change the fact that ALL tests, whether an LDT or test kit, occasionally have false readings.  Early in my cancer journey, a blood test said my blood glucose was 30-something (normal range is 70-120).  The doctor called me late at night, concerned that I was seriously ill (if not dead).  I was fine.  The test result was incorrect.

The FDA held a workshop on the proposed regulations on January 8-9, 2015 (see agenda day 1 and day 2 videos).  During the two days of presentations, several issues were raised :

  • PACE of scientific discovery: Our knowledge of cancer-causing genes, how they affect the body, and ways of detecting them is evolving rapidly. FDA regulations move slowly; approvals usually takes years.
  • VARIETY of labs producing LDTs: Some large for-profit labs that offer genomic tests might be able to afford the cost of additional personnel and fees to comply with proposed FDA regulations. Smaller labs such as those associated with hospitals might not be able to absorb the additional costs and might be forced to close.
  • SCOPE of tests: Determining which LDTs to perform, validating results, and applying the results to treatment is the practice of medicine, which the FDA is prohibited from regulating. Also, the FDA seeks to regulate LDTs as medical devices, but laboratory professionals claim LDTs are not medical devices because they involve medical judgment.

Our understanding of existing oncogenes (ALK, EGFR, BRAF, etc.) and their associated targeted therapies continues to evolve even after the FDA approves companion tests to detect targetable mutations.  It’s not unusual for an LDT to be developed that detects a new variation of an oncogene not detected by the FDA-approved test.  Must cancer patients wait years until the FDA approves the new LDT before they can receive an effective targeted therapy?  Most stage IV cancer patients can’t afford to wait that long.

Here’s an example of how pace, variety, and scope can make a difference for patients.  In a presentation to the FDA on January 8, University of Colorado pathologist Dara Aisner, MD, PhD, shared the following:

“This Kaplan-Meier Curve demonstrates survival benefit for patients with metastatic melanoma treated with vemurafinib [vs dacarbazine] when they have an ‘atypical’ mutation – V600K.  Of note, 34% of the V600K mutation positive patients in this cohort were classified as NEGATIVE by an FDA approved assay and were only detected using a non-FDA approved assay. … This is an example of the clinical validity that evolves rapidly with time.  Determining clinical validity is the physician’s job.”

 Survival Analysis of patients with BRAF V600K mutation

As you can see from this example, restricting the targeted therapy vemurafinib only to patients identified by the FDA-approved test would have prevented many patients from receiving effective treatment.  The current FDA approval process takes years, is resource intensive, and could potentially interfere with the practice of medicine.  Dr. Aisner has stated that if the FDA’s proposed regulations are enacted, her lab at the University of Colorado might have to close or at least stop providing many of its tests.

Another example: the current FDA-approved test for detecting ALK rearrangements in lung cancer is only approved for testing biopsied tumor tissue.  If a patient doesn’t have sufficient biopsied tissue for testing, sometimes other sources of cells (such as fluid collected from a pleural effusion or a lymph node) can provide enough cells for ALK testing.  Many labs have independently validated the test on such specimens.  However, under the proposed FDA regulations, testing these alternative specimens would no longer be allowed unless a lab submits the test to the FDA and obtains its approval.  As a result, some lung cancer patients would have more limited options for testing, and might require additional, potentially dangerous biopsies in order to obtain tumor tissue.

Note that the proposed regulations include an exemption for LDTs for unmet needs that would allow the use of non-FDA reviewed LDTs when no approved LDT is available for the condition.  For instance, ROS1 NSCLC (my diagnosis) does not have an approved LDT, so patients could be tested with an unapproved LDT.

This proposed regulation has the potential to prevent targeted therapy treatment for thousands of patients with cancers and other diseases.  We hope you’ll join us for #LCSM Chat on Thursday January 15 at 8 PM.

Comment period for the proposed FDA Framework for Regulation of Laboratory Developed Tests (LDTs) closes on February 2, 2015. Please let the FDA know what you think by submitting your comments ASAP to (be sure to include the docket number FDA-2011-D-0360).  You can also submit comments electronically here.


Overview Articles:

Opinions Divided on Proposed FDA LDT Regulations (Genetic Engineering and Biotechnology News)

To regulate or not: FDA hears arguments on medical tests (New England Center for Investigative Reporting)


Supporting the FDA’s Proposed Framework:

Advamed (medical device manufacturer’s trade association)

American Association of Cancer Research

American Cancer Society Cancer Action Network, American Heart Association, and Ovarian Cancer National Alliance

American Society of Clinical Oncology

Journal of American Medical Association (yes)


Opposing the FDA’s Proposed Framework:

American Clinical Laboratory Association

ARUP Laboratories

Association for Molecular Pathology (white paper)

Joint Letter to FDA (signed by 51 organizations, societies, and laboratory directors)

Journal of American Medical Association (no)