Telemedicine to Dhealth

March 9, 2015: Fox interviews Theranos and Cleveland Clinic.

http://video.foxbusiness.com/v/4100844587001/theranos-cleveland-clinic-ceos-on-innovation-partnership-/?#sp=show-clips

Note: These are my running notes and not a transcript.

Elizabeth Holmes, CEO Theranos, Toby Cosgrove MD, CEO Cleveland Clinic.

TC:  Theranos has developed some new technology with the opportunity to reduce the cost and trauma of lab tests.  A real game changer for patients, and improve access.

FOX:  The one thing people hate, "giving blood."

EH:  We've focused on bringing access to actionable health information to everyone, driven by lab data, and people have such a fear of having blood drawn.  We've spent 12 years redeveloping every lab test for tiny samples.  And access to tests that uniform transparent prices, regardless of insurance, and very low pricing, 50% of Medicare.  We've dropped further for some tests, to 90% off Medicare.  Everyone can afford getting tested. Moves us to the dream of early detection.

FOX:  We are getting in front of disease.  I was at your innovation summit, Craig Venter said, we'll live into the second century (> age 100).

TC:  That's correct, and people won't be afraid of a finger prick, and it will be cheaper.  For hospital patients, we can make them anemic. We avoid that.

FOX:  Elizabeth, you already have Wellness Centers, in California, in Arizona.  How come, the hospital, they take an enormous amount of blood?

EH:  It's effectively an infrastructure unchanged for a long time.  We have redeveloped the infrastructure.  We can do the combinations of tests from tiny samples.  We redeveloped the whole infrastructure.   It's a privilege to partner with Cleveland Clinic.  Not just outpatient, but inpatient. the exact same technology as outpatient world.

FOX:  We talked about the outpatient world, Walgreens.  You use it differently?

TC:  Think about a new born baby, if you can do a two drop heel prick, a huge advantage.  Tremendous potential.  Inpatient and outpatient.

FOX:  It's a marriage of health care and technology.  The worlds are merging.

TC:  We see tremendous opportunity with new technology - Theranos is one.  We also see opportunities with IT, looking at collecting the knowledge, the Big Data.  We see virtual visits.  Take the care to the patient.   We've done that with stroke, a CT scanner in an ambulance.  It's coming together as rapidly as we can.  We've been less technologically facile in the past.

EH:  I deeply believe, the answer to health challenges lies in the individual, engaging them, in the management of health, the more we can impact outcomes.  Access, engagement, dovetails with technology, you can connect with people and in our work getting them more and more focused on the power of this information, that they've never paid much attention to.  They know more about their credit cards than their lab data.  But you can do alot from a lifestyle perspective, you see the powerful change in your blood.  We provide technology, they allow engagement, connect to the healthcare process.  We are developing the retail Wellness Centers, a wonderful experience for patients.

TC:  You asked about tech and virtual reality.  We are partnering with Microsoft, VR goggles, for teaching, someday for patients.

FOX: It's exciting.  It's consumerism.  Taking responsibility.  Final question: What about the privacy end?  All that info in that drop of blood?

EH:  That's critical. It doesn't tell the world - individuals own their own data, we will never sell data or advertise on it.  We can delete it on request, or transfer it on request.  

TC:  The privacy of health information is better off electronic than a paper chart just floating around a hospital with access by many people.

FOX: Phenomenal.  Thanks.

Arizona HB2645 Direct Access testing.

Note:  Some FDA IVD test approvals require the test to be ordered by a physician, which would ?likely supersede state law.  For a news article, see here.

Accessed 03/05/2015.

http://www.azleg.gov/legtext/52leg/1r/bills/hb2645p.htm

HB 2645

Introduced by Representative Carter

AN ACT

AMENDING SECTION 36‑466, ARIZONA REVISED STATUTES; AMENDING TITLE 36, CHAPTER 4.1, ARTICLE 2, ARIZONA REVISED STATUTES, BY ADDING SECTION 36‑468; RELATING TO CLINICAL LABORATORIES.

(TEXT OF BILL BEGINS ON NEXT PAGE)

Be it enacted by the Legislature of the State of Arizona:

Section 1.  Section 36-466, Arizona Revised Statutes, is amended to read:

36-466.  Advisory committee on clinical laboratories; membership; duties

A.  The advisory committee on clinical laboratories is established consisting of the following members:

1.  Four physicians who are licensed pursuant to title 32, chapter 13 or 17 and who are actively engaged in the practice of medicine.  The director shall appoint these members.

2.  Two physicians who are licensed pursuant to title 32, chapter 13 or 17 and who are employed by a clinical laboratory as pathologists.  The director shall appoint these members.

3.  The director or the director's designee.

B.  The committee shall:

1.  Annually select a chairperson and vice‑chairperson from among its members.

2.  Advise the department in developing a list of direct access tests. The department shall make the list of direct access tests available to the public.

3.  2.  Advise the department on the use and renewal of standing orders.

4.  3.  Conduct regular meetings at the call of the chairperson or a majority of the committee members.

C.  The department's designation of a test as a direct access test does not require that the test be covered by a health insurance plan or product pursuant to title 20 or by any program administered by the Arizona health care cost containment system administration pursuant to chapter 29 of this title.

D.  C.  The department shall adopt rules based on the recommendations of the advisory committee.

E.  D.  Committee members are not eligible to receive compensation or reimbursement of expenses.

F.  E.  The department shall provide necessary staff services to the committee.

G.  F.  The appointed committee members serve three‑year terms.

H.  For the purposes of this section, "direct access tests" means tests that may be obtained without a physician referral including tests that have been granted waived status under the federal clinical laboratory improvement amendments of 1988 (P.L. 100‑518).  Direct access tests do not include tests that are required to be reported to this state for public health and safety reasons.

Sec. 2.  Title 36, chapter 4.1, article 2, Arizona Revised Statutes, is amended by adding section 36-468, to read:

36-468.  Laboratory testing without physician order; results; report; immunity; definition

A.  A PERSON MAY OBTAIN ANY LABORATORY TEST WITHOUT A PHYSICIAN'S REQUEST OR WRITTEN AUTHORIZATION.

B.  IF A LABORATORY TEST OF A PERSON IS CONDUCTED BY OR UNDER THE SUPERVISION OF A PERSON OTHER THAN A PHYSICIAN AND NOT AT THE REQUEST OR WITH THE WRITTEN AUTHORIZATION OF A PHYSICIAN, ANY REPORT OF THE TEST RESULTS SHALL BE PROVIDED BY THE PERSON CONDUCTING THE TEST TO THE PERSON WHO WAS THE SUBJECT OF THE TEST.  THE REPORT SHALL STATE IN BOLD TYPE THAT IT IS THE RESPONSIBILITY OF THE PERSON WHO WAS TESTED TO ARRANGE WITH THE PERSON'S PHYSICIAN FOR CONSULTATION AND INTERPRETATION OF THE TEST RESULTS.

C.  A PHYSICIAN IS NOT LIABLE FOR THE FAILURE TO REVIEW OR ACT ON THE LABORATORY TEST RESULTS OF ANY PATIENT IF THE PHYSICIAN NEITHER REQUESTED NOR AUTHORIZED THE LABORATORY TEST.

D.   THIS SECTION DOES NOT REQUIRE THAT A LABORATORY TEST BE COVERED BY A HEALTH INSURANCE PLAN OR PRODUCT PURSUANT TO TITLE 20 OR BY ANY PROGRAM ADMINISTERED BY THE ARIZONA HEALTH CARE COST CONTAINMENT SYSTEM ADMINISTRATION PURSUANT TO CHAPTER 29 OF THIS TITLE.

E.  FOR THE PURPOSES OF THIS SECTION, "PHYSICIAN" MEANS A PERSON WHO IS LICENSED PURSUANT TO TITLE 32, CHAPTER 13 OR 17.

Sec. 3.  Rulemaking; exemption

The department of health services shall amend or adopt rules to address the changes in direct access laboratory testing as enacted by this act.  For this purpose, the department is exempt from the rulemaking requirements of title 41, chapter 6, Arizona Revised Statutes, for one year after the effective date of this act.

AMP's language on clinically relevant DTC genetic tests.

In early 2015, the AMP updated its recommendations for DTC genetic testing.   It supported "access to clinically meaningful genetic testing" on a "direct access" (no prescription) basis, with several conditions.  For the full document see here.   What the AMP wrote is not far off from what the FDA required of 23andMe (here).

AMP Supports:

 Direct access to clinically meaningful genetic testing may add value to patients and consumers, when certain standards are met. Accordingly, AMP now supports direct access genetic testing for clinically meaningful tests under the following conditions:

• The association between the genetic marker for which testing is performed and the relevant disease must be robust and supported by strong scientific evidence in the peer reviewed literature, and/or be based on evidence referenced or annotated in current genetic/genomic databases. 
• Testing should comply with the CLIA statute and regulations, and all applicable state and federal laws and regulations. 
• Transparency regarding the analytical and clinical validity of the tests should be present in all marketing materials and included in the report. Specifications include but are not limited to, analytical and clinical sensitivity/ specificity, and the limitations of assay. These should be described in terms understandable to an educated lay reader (see next bullet point). In addition, the underlying data and analytical methodology, including computational and/or statistical methods employed, power analyses, confidence analyses, etc. upon request should be readily available to health professionals. 
• Reporting of test results and the limitations of the test should be in lay language. Additionally, the report should include an interpretation of the finding and describe its significance for the consumer’s health status. 
• Test validation and interpretation should be performed by certified molecular laboratory professionals. 
• AMP strongly supports referral for genetic counseling services and the provision of educational materials. Test providers should encourage genetic counseling as an additional step for consumer education. Resources such as referrals to the National Society of Genetic Counselors’ directory or through genetic counseling contracting services are considered appropriate. 
• Direct access laboratories should recommend that consumers discuss their test results with their physicians. 

For my blog on a half-dozen recent AMP positions (as of early 2015) see here.

The FDA and its Classification of Clinical Laboratory Diagnostic Tests.

Like CLIA, the FDA has a fairly dated-appearing classification system for diagnostic tests.

FDA regulations are found at CFR 21.

Subpart H is devices is found at 21 CFR 800-898 (radiology follows with mammography at 900.X and other radiology health at 10XX.).  

Within devices, 862 is clinical chemistry, 864 is hematology and pathology, and 866 is immunology and microbiology.

Most entries are specific.  for example, 862.110 is a direct bilirubin test system.  866.5210 is a ceruloplasmin immunology test system.   Tucked in alphabetic order between Biocarbonate Test System (866.1160) and Catecholamines (866.1165) is "Cardiac allograft gene expression profiling test system," e.g. Allomap (866.1163).

However, some categories are quite broad.  864.1850 is "dye and chemical solution stains" which may be "synthetic or natural dyes" and are "exempt" as Class I devices.   864.1860 is "immunohistochemistry" which may be Class I, II or III depending on indication.

• Class I IHC - "IHC's that provide the pathologist with adjunctive diagnostic information that may be incorporated into the pathologist's report, but that is not ordinarily reported to the clinician as an independent finding...used after the primary diagnosis of a tumor has been made...to subclassify tumors, such as keratin."
• Class II IHC - "Detection...to provdie prognostic or predictive data that are not directly confirmed by routine histopathologic control specimens...ordinarily reported as independent diagnostic information to the ordering clinician and the claims asasociated with these data are widely accepted and supported by valid scientific evidence...such as hormone receptors in breast cancer."
• Class III IHC - "Intended for any use not described above."

EGFR FISH has its own category, however, at 864.1870:

§864.1870   Early growth response 1 (EGR1) gene fluorescence in-situ hybridization (FISH) test system for specimen characterization.
(a) Identification. An early growth response 1 (EGR1) gene fluorescence in-situ hybridization (FISH) test system for specimen characterization is a device intended to detect the EGR1 probe target on chromosome 5q in bone marrow specimens from patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). The assay results are intended to be interpreted only by a qualified pathologist or cytogeneticist. These devices do not include automated systems that directly report results without review and interpretation by a qualified pathologist or cytogeneticist. These devices also do not include any device intended for use to select patient therapy, predict patient response to therapy, or to screen for disease as well as any device with a claim for a particular diagnosis, prognosis, monitoring, or risk assessment.
(b) Classification. Class II (special controls). The special controls for this device are:
(1) Premarket notification submissions must also include the following information:
(i) A detailed description of all probes included in the kit;
(ii) Purpose of each probe;
(iii) Probe molecular specificity;
(iv) Probe specificity;
(v) Probe limits;
(vi) Probe sensitivity;
(vii) Specification of required ancillary reagents, instrumentation, and equipment;
(viii) Specification of the specimen collection, processing, storage and slide preparation methods;
(ix) Specification of the assay procedure;
(x) Specification of control elements that are incorporated into the recommended testing procedures;
(xi) Specification of risk mitigation elements: Description of all additional procedures, methods, and practices incorporated into the directions for use that mitigate risks associated with testing;
(xii) Specification of the criteria for test result interpretation and reporting;
(xiii) Device analytical sensitivity data;
(xiv) Device analytical specificity data;
(xv) Device reference limit data;
(xvi) Device precision/reproducibility data;
(xvii) Device stability data to include:
(A) Real-time stability,
(B) Freeze-thaw stability,
(C) Transport and temperature stability,
(D) Post-hybridization signal stability,
(E) Photostability of probe, and
(xviii) Documentation that demonstrates the clinical validity of the device. The documentation must include data from clinical studies, a minimum of two peer-reviewed published literature references using the specific device seeking marketing clearance, or both. Documentation for the clinical studies and peer-reviewed published literature references cited must include the following elements:
(A) Documentation that the sponsor's probe was used in the literature reference,
(B) Number and type of specimens,
(C) Target population studied,
(D) Upper reference limit, and
(E) Range of positive probe results.
(2) Your §809.10(b)(12) of this chapter compliant labeling must include a statement summarizing the data identified in paragraphs (b)(1)(xiii) through (xviii) of this section and a description of the studies supporting the information, including the pre-specified acceptance criteria for these performance studies, justification for the pre-specified acceptance criteria, and whether the pre-specified acceptance criteria were met.
(3) Your §809.10 of this chapter compliant labeling must include:
(i) A warning that reads “The assay results are intended to be interpreted only by a qualified pathologist or cytogeneticist.”
(ii) A warning that reads “This device is not for high-risk uses such as selecting therapy, predicting therapeutic response or disease screening.”
(iii) A warning that reads “The use of this device for diagnosis, monitoring or risk assessment has not been established.”
[79 FR 52196, Sept. 3, 2014]

Whew! 

As noted earlier, the 866 category contains dozens and dozens of immunologic test names (tryptase system, thyroid autoantibody system, transferrin system, etc).  

Then sudden appears 866.5900, the Illumina CFTR genetic sequencing tes category (here).  

The 23andMe genetic screening tests will be in a generic, genetic test carrier screening category to appear next in series, at 866.5940.

Tumor associated antigens have their own category, at 866.6010.  

Class II (special controls). Tumor markers must comply with the following special controls: (1) A guidance document entitled “Guidance Document for the Submission of Tumor Associated Antigen Premarket Notifications (510(k)s) to FDA,” and (2) voluntary assay performance standards issued by the National Committee on Clinical Laboratory Standards.

Note that you "must comply with" the "voluntary standards" of the NCCLS.   

This tumor-associated immunology test system category is where CMS has also placed gene expression tests for breast cancer prognosis (e.g. Mammaprint, Prosigna) at 866.6040 and the Ova1 and ROMA ovarian mass tests, at 866.6050.  

30 Recent PUBMED Citations on the topic "Real World Evidence"

About 30, only lightly-selected hits from PUBMED on the topic "real world evidence."

1/26/2015 Interview with Liz Mansfield, FDA, on LDTs.

Find the full audio podcast at Mendelspod.com, here.

Below are some detailed notes I jotted down on a running basis while listening to the interview - the notes below are NOT a transcript.