Personalized MedicinePersonalized MedicineDirect to Consumer MarketingDirect to Consumer MarketingAnd FDAAnd FDA

Margaret Foster Riley, JDUniversity of Virginia School of LawMay 30, 2008

Personalized MedicinePersonalized MedicineHope or Hype?Hope or Hype?As we have discussed over the

last two days, personalized medicine offers great potential—but it’s far from fully realized

Even pharmocogenic success stories are “limited.”◦Her2/neu testing◦CYP450 testing

NEJM April 2009

Personalized MedicinePersonalized MedicineHope or Hype?Hope or Hype?NEJM April 2009

◦Great majority of newly identified risk-marker alleles confer very small relative risks

◦Those relative risks are not stable estimates due to the likelihood of identification of new risk loci

But the potential for preventive therapies, geared to the right population, is beguiling

Some risk loci may already be more stable◦Type 1 diabetes and HLA loci?

Personalized MedicinePersonalized MedicineHope or Hype?Hope or Hype?Once risk estimates are more stable,

the usefulness of genetic screening will need to be considered for each disease, and recommendations about potential interventions for people whose predicted risk exceeds a specified threshold (Source: Kraft et al. NEJM April 2009)

Who will decide and how will that be decided?

Personalized MedicinePersonalized MedicineHHS and its subsidiary agencies, FDA,

CMS etc., have long been aware of the critical questions that personalized medicine brings to the regulation of medical care and products—but little has actually been done

FDA’s “Critical Path Initiative” and NCTR’s Strategic Plan (March 2009) both focus on personalized medicine initiatives

FDA and Personalized FDA and Personalized MedicineMedicineThe Big PictureThe Big PictureSince 1962 FDA has regulated

drugs—and since 1976—devices—requiring a showing of safety and efficacy

The question in some instances will become “safe and effective” for whom?

Personalized MedicinePersonalized MedicineGroups promoting personalized

medicine have lobbied House Democrats hard regarding the Comparative Effectiveness Research Act of 2009

Research would study how treatments affect people based on gender, race, age and medical conditions

Some argue that every clinical trial comparing clinical treatments should include DNA sequencing of every volunteer

Regulation of Genetic Regulation of Genetic TestingTestingOne of the great challenges of

personalized medicine will be the development of “valid” testing—both for◦Practitioners◦And Consumers

Secretary’s Advisory Committee on Genetic Testing and GAO have recommended better regulation of genetic testing◦

Regulation of Genetic Regulation of Genetic TestingTesting

Many tests are already being commercially offered—not just to practitioners but also to consumers…

Is the horse already out of the barn?

Personalized MedicinePersonalized MedicineThose advocating inclusion of

personalized medicine in health reform packages argue that it will allow targeted treatments, avoid unnecessary adverse events, and save money by treating only those who will benefit…

But can it possibly achieve those goals?

Does personalized medicine save money?

RegulatorsRegulatorsCDC—to the extent involves public health

◦ EGAPPCMS—CLIA—with exceptionsFDA—to the extent fit within device

regulationFTC—advertising (although FDA plays a

role)

NIH, HRSA and AHRQ support research and therefore regulate supported research

FDA regulationFDA regulationLaw as ArchitectureFDA regulates products not practiceFDA has never defined “genetic test.”FDA regulates genetic tests as devices

—but not all genetic testing is subject to the device regulatory rubric

Devices are subject to different levels of control◦ 510K vs. PMA◦ Class 1-general controls◦ Class II◦ Class III

FDA RegulationFDA RegulationSome argue that genetic tests are no different

from other laboratory tests and should be regulated like other laboratory tests

Others argue that genetic tests, although having great potential benefit, have potential to cause great harm without adequate assurance of safety and effectiveness. In some instances, these tests may be the sole basis for making a clinical decision with significant consequences

The majority of genetic testing is subject to no oversight to ensure that they are safe and effective

FDA RegulationFDA RegulationGenetic tests fit within the definition of

in vitro diagnostics◦General-purpose reagents◦Analyte specific reagents (ASRs)◦Test systems or test kits

ASRs are regulated as restricted devices◦But regulatory compliance is poor

IVD test systems or test kits are manufactured for a specific laboratory test◦have specific intended use

FDA RegulationFDA RegulationLaboratory Developed Tests

◦Based on an in-house protocol and assembled by the laboratory for its own use

◦While specific reagents may be directly regulated, FDA has not directly regulated LDTs

◦CLIA rules do not evaluate the safety and effectiveness of the individual tests performed

FDA RegulationFDA RegulationTension in FDA regulation (or lack of)

of LDTs: ◦Recognition that there is unpredictable

quality and there may be a risk to public health

◦Mechanism for bringing novel, highly specialized tests, for relatively rare diseases

2006 draft guidance attempted to regulate IVDMIAs◦Characterized by proprietary algorithms

that generate patient specific results based on multiple pieces of data

FDA struggles with the FDA struggles with the appropriate level of regulationappropriate level of regulation “FDA considered designating as Class III devices

those ASR's that would be marketed independently for use in tests intended for use in overtly healthy people to identify a genetic predisposition to a dementing disease, or to fatal or potentially fatal medical disorders (e.g., cancers or Alzheimer's disease), in situations where penatrance is poorly defined or variable and latency is five years or longer. However, after reviewing the comments and currently available information, FDA has not yet identified criteria that would logically distinguish among genetic tests in order to determine which have the requisite impact to trigger more stringent controls.”

Source 62 Fed. Reg. 62,245-46

State RegulationState RegulationNew York as a model

◦ pre-market review process for genetic tests

◦Some better than none

Direct to Consumer Direct to Consumer MarketingMarketingIn 2002 Myriad Genetics

launched the first major direct to consumer genetic testing campaign for BRACanalysis

Since then there has been explosion of sorts—in both print, television and especially, internet advertising

Some of the leading Some of the leading companiescompanies23andMENavigenicsdeCode GeneticsDNA Direct

Direct to Consumer Direct to Consumer MarketingMarketingSome companies market clinically

available tests for disorders such as hemochromatosis and cystic fibrosis

Some websites offer genetic tests for nutrition, behavior and aging. A consumer may be offered cosmetics or nutraceuticals based on her “genetic make up”

Direct to Consumer Direct to Consumer MarketingMarketingGenetic tests are marketed not

only for health risk information but for genealogy, studying ancestry and as tools for social networking

Sponsored LinksPersonalized Medicine

◦ www.ageofpersonalizedmedicine.org Learn about a new era of healthcare and improving patient health

Genetic Tests◦ www.DNAtesting.com/Genetic_Tests

Purchase Genetic Tests Now available at a store near you!

Genetic Testing on Kids◦ www.ResponsibilityProject.com Do You Think

It Is Responsible To Use Genetic Testing on Kids?

Matrix Genomics' founding mission is to empower you to enhance your life and life expectancy.

Are you predisposed for developing breast cancer? Do you have an inherited risk for heart attack or Alzheimer's disease? A DNA home

testing kit from Matrix Genomics—a personal genomics company—can identify your propensity for developing common hereditary health

conditions, enabling you and your doctor to develop a personalized medicine plan for preventative care that's tailored to your DNA profile. By

arming you with powerful knowledge about your genetic risk factors, Matrix Genomics brings the science of genetics from the lab to real life.

Current Genetic Risk Assessment Tests Alzheimer's Disease»

Breast Cancer»Heart Attack»

From 23andmeOur customers are saying..."I thought how fascinating if I could

know more about my future. I should know. I should be aware for myself. For my children. If there's something that I could prevent for the future, or live my life in a different way, why not learn? Why not help myself? And be knowledgeable in that information for my health and well-being."

~ Susan M.

Direct to Consumer Direct to Consumer MarketingMarketingAdvertisers vary as to whether

they require a consumer to involve health care professionals or not◦Even those that do, do not require

expertise in genetic counselling

Arguments Posed Supporting Arguments Posed Supporting DTC Genetic TestingDTC Genetic TestingGenetic information is a “fundamental part

of you” and people have a right to it“It doesn’t say you have a disease…It says

you carry a genetic predisposition for the disease and should talk with a health care professional”

Patients deserve direct access to their health information without a physician intermediary

Source: Magnus et al. Genome Medicine 2009

Consumer-Directed GenomicsConsumer-Directed GenomicsOne ViewOne ViewAn extra medical surveillance practice that

has some preventive value and is complementary to traditional forms of health surveillance and patient care.

By engaging and educating people in their health care, they will be better served

The problem is not consumer-directed genomics itself, but establishing appropriate standards and practices for commercial providers

Consumer-Directed GenomicsConsumer-Directed Genomicsand Anotherand Another Our ability to read the genome is well

ahead of our ability to know whether medical intervention based on such a reading does more good than harm.

We can be sure that haphazard genetic testing will needlessly make well people worry about becoming sick.

We need more research, not pricey genomic scans.

FTC 2006 Consumer NoticeWarns against increased

(especially internet) salesBut who reads it?

Should the FTC do more?

State Law RegulationState Law RegulationAs of 2008, 25 state and the District of

Columbia permit DTC laboratory testing without restriction; 13 states categorically prohibit it, 12 states (including New York and California) permit some testing—these likely do not include genetic testing—without medical supervision

California and New York have begun sending “cease and desist” orders to genetic testing companies

Free Speech ConsiderationsRegulations affecting commercial speech

do not violate the First Amendment if: 1. The regulated speech concerns an illegal activity, 2. The speech is misleading, or 3. The government's interest in restricting the speech is substantial, the regulation in question directly advances the government's interest, and the regulation is narrowly tailored* to serve the government's interest.

*The original Central Hudson test required that the government prove the regulation was no more restrictive of speech than necessary to serve its interest.

Questions of LiabilityQuestions of LiabilityLearned Intermediary Doctrine