mp-2.236 general approach to genetic testing · 2015. 5. 13. · medical policy policy title...

MEDICAL POLICY

POLICY TITLE GENERAL APPROACH TO GENETIC TESTING

POLICY NUMBER MP- 2.326

Page 1

Original Issue Date (Created): March 25, 2014

Most Recent Review Date (Revised): March 25, 2014

Effective Date: August 1, 2014

I. POLICY

This policy applies only if there is not a separate Medical Policy that outlines specific

criteria for testing. If a separate policy does exist, then the criteria for medical necessity in

that policy supersede the guidelines in this policy.

Genetic testing classified in one of the categories below may be considered medically

necessary when all criteria are met for each category.

Medical criteria

Genetic testing is considered medically necessary for a genetic or heritable disorder when the

following are met:

1. Diagnostic testing for genetic or heritable mutations of an affected individual

an association of the marker with the disorder has been established AND

symptoms of the disease are present AND

a definitive diagnosis cannot be made based upon history, physical

examination, pedigree analysis, standard diagnostic studies/tests AND

the clinical utility of a diagnosis has been established, (see Appendix) for

example by demonstrating that a definitive diagnosis will lead to changes in

clinical management of the condition, changes in surveillance or changes in

reproductive decision making, and the changes will lead to improved health

outcomes AND

establishing the diagnosis by genetic testing will end the clinical work-up for

other disorders

POLICY PRODUCT VARIATIONS DESCRIPTION/BACKGROUND

RATIONALE DEFINITIONS BENEFIT VARIATIONS

DISCLAIMER CODING INFORMATION REFERENCES

POLICY HISTORY

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2. Risk assessment

a. Predictive and presymptomatic:

an association of the marker with future disorder has been established AND

the clinical utility has been established (see Appendix), for example by

demonstrating that testing will lead to improved health outcomes based on

prevention or early detection strategies

b. Carrier testing

an association of the marker with the disorder has been established AND

the genetic disorder is associated with a potentially severe disability or has a lethal natural history AND

the clinical utility has been established (see Appendix), for example by demonstrating that the results of the test will have an impact on family planning

3. Prognostic testing

an association of the marker with the natural history of the disease has been

established AND

the clinical utility of identifying the mutation has been established, for example

by demonstrating that it will lead to changes in clinical management of the

condition or changes in surveillance

4. Genetic variants that alter response to treatment or to an environmental factor

a. Constitutional (germline) testing:

the association of the marker with a phenotype/metabolic state that relates to drug efficacy or adverse drug reactions has been established AND

the clinical utility has been established (see Appendix), for example by demonstrating that the results of the genetic test will impact clinical decision

making and will be expected to result in improved clinical outcomes for the patient

based upon drug selection or dosage

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b. Tissue-specific or tumor testing:

the association of a mutation with response to a particular drug has been

established AND

the clinical utility has been established (see Appendix), for example by

demonstrating that the patient is a candidate for targeted drug therapy which

is associated with a specific mutation

Genetic testing that does not meet the criteria for a specific category is considered

investigational or not medically necessary, according to the standard definitions used for these

terms (see Policy Guidelines).

Other Testing

“At-home” or “direct-to-consumer” genetic testing

“At-home” or “direct-to-consumer” genetic testing is considered investigational as there is

insufficient evidence to support a conclusion concerning the health outcomes or benefits associated

with this procedure.

Frequency of testing

In the absence of specific information regarding advances in the knowledge of mutation

characteristics for a particular disorder, the current literature indicates that genetic tests for inherited

disease need only be performed once per lifetime of the patient.

Policy Guidelines

Genetic testing is considered investigational when there is insufficient evidence to determine

whether the technology improves health outcomes.

Genetic testing is considered not medically necessary when:

testing is not considered standard of care, such as the clinical diagnosis can be made without

the use of a genetic test

testing is not clinically appropriate for the patient’s condition, for example, when it would

not change diagnosis and/or management. Other situations where testing is not clinically

appropriate include, but are not limited to:

o testing is performed entirely for non-medical (e.g., social) reasons

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o testing is not expected to provide a definitive diagnosis that would obviate the need

for further testing.

testing is performed primarily for the convenience of the patient, physician or other health

care provider.

testing would result in outcomes that are equivalent to outcomes using an alternative

strategy, and the genetic test is more costly.

Cross-reference: Also see Appendix 2 for additional policies related to genetic testing.

MP-2.323 General Approach to Evaluating the Utility of Genetic Panels

MP-7.009 Preimplantation Genetic Testing

MP- 2.242 Chromosomal Microarray (CMA) Analysis for the Genetic Evaluation of Patients

with Developmental Delay/Intellectual Disability or Autism Spectrum Disorder

MP-2.050 Diagnostic Testing and Risk Assessment for Alzheimer’s disease

MP-2.233 Genetic Testing for Congenital Long QT Syndrome

MP-2.304 Pervasive Developmental Disorders

II. PRODUCT VARIATIONS TOP [N] = No product variation, policy applies as stated

[Y] = Standard product coverage varies from application of this policy, see below

* Benefits are available for specialized diagnostic genetic testing when it is medically necessary

to diagnose and/or manage a patient’s medical condition. However, genetic screening is not

covered.

* The FEP program dictates that all drugs, devices or biological products approved by the U.S.

Food and Drug Administration (FDA) may not be considered investigational. Therefore, FDA-

approved drugs, devices or biological products may be assessed on the basis of medical

necessity.

** Refer to Centers for Medicare and Medicaid Services (CMS) National Coverage Determination

(NCD) 190.3, Cytogenetic Studies. Also see Novitas Solutions Local Coverage Determination

(LCD) L34796 Biomarkers for Oncology and L33640 Biomarkers Overview.

[N] Capital Cares 4 Kids [N] Indemnity

[N] PPO [N] SpecialCare

[N] HMO [N] POS

[Y] SeniorBlue HMO** [Y] FEP PPO*

[Y] SeniorBlue PPO**

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III. DESCRIPTION/BACKGROUND TOP

There are numerous commercially available genetic tests, including those used to guide

intervention in symptomatic or asymptomatic individuals, to identify individuals at risk for

future disorders, to predict the prognosis of diagnosed disease and to predict treatment

response. This concept policy offers a framework for evaluating the utility of genetic tests, by

classifying the types of genetic tests into clinically relevant categories and developing criteria

that can be used for evaluating tests in each category.

Purpose The purpose of this policy is to provide assistance in evaluating the utility of genetic

tests. In providing a framework for evaluating genetic tests, this policy will not attempt to determine the clinical utility of genetic testing for specific disorders. Rather, it provides

guidelines that can be applied to a wide range of different tests.

This policy does not include cytogenetic testing (karyotyping), biochemical testing, or

molecular testing for infectious disease.

This policy does not address prenatal testing. Prenatal testing involves particular ethical

concerns that are not easily addressed via review of the scientific evidence.

Definitions

Genetic testing: Genetic testing involves the analysis of chromosomes, DNA

(deoxyribonucleic acid), RNA (ribonucleic acid), genes or gene products to detect inherited

(germline) or non-inherited (somatic) genetic variants related to disease or health.

Carrier testing: A carrier of a genetic disorder has one abnormal allele for a disorder. When

associated with an autosomal recessive or X-linked disorder, carriers of the causative mutation

are typically unaffected. When associated with an autosomal dominant disorder, the individual

has one normal and one mutated copy of the gene, and may be affected with the disorder, may

be unaffected but at high risk of developing the disease later in life, or the carrier may remain

unaffected because of the sex-limited nature of the disease.

Carrier testing may be offered to individuals: A) who have family members with a genetic

condition; B) who have family members who are identified carriers; and C) who are members

of ethnic or racial groups known to have a higher carrier rate for a particular condition.

Germline mutations: Mutations that are present in the DNA of every cell of the body, present

from the moment of conception. These include cells in the gonads (testes or ova) and could

therefore be passed on to offspring.

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Somatic mutations: Variations that occur with the passage of time, and are restricted to a

specific cell or cells derived from it. If these variations are limited to cells that are not in the

gonads, these variations will not be passed on to offspring.

Pharmacogenomics: The study of how an individual’s genetic makeup affects the body’s

response to drugs.

IV. RATIONALE TOP

General principles of genetic tests

The test should be cleared or approved by the U.S. Food and Drug Administration (FDA), or

performed in a Clinical Laboratory Improvement Amendment (CLIA) -certified laboratory.

Peer-reviewed literature on the performance and indications for the test should be available.

This evaluation of a genetic test focuses on 3 main principles: 1) analytic validity, which refers

to the technical accuracy of the test in detecting a mutation that is present or in excluding a

mutation that is absent; 2) clinical validity, which refers to the diagnostic performance of the

test (sensitivity, specificity, positive and negative predictive values) in detecting clinical disease;

and 3) clinical utility, i.e., how the results of the diagnostic test will be used to change

management of the patient and whether these changes in management lead to clinically

important improvements in health outcomes.

Types of genetic tests addressed in this policy

1. Diagnostic testing for genetic or heritable mutations in a symptomatic individual. This

refers to a molecular diagnosis defined by the presence of a known pathologic mutation.

For the purposes of genetic testing, a symptomatic individual is defined as an individual

with a clinical phenotype that is correlated with a known pathologic mutation.

2. Risk assessment for genetic and heritable mutations.

a. Predictive and presymptomatic types of testing are used to detect gene mutations associated with disorders that appear after birth, usually later in life. These tests can

be used in individuals with a family history of a genetic disorder, but who

themselves have no features of the disorder at the time of testing. Predictive testing

can identify mutations that increase an individual’s risk of developing disorders with

a genetic basis, such as certain types of cancer or cardiovascular disease.

Presymptomatic testing can determine whether a person will develop a genetic

disorder, before any signs or symptoms appear, by determining whether an

individual has a genetic mutation that may lead to development of the disease.

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b. Carrier testing is performed in an individual who may be at risk of passing on a mutation to their children. This type of testing is offered to individuals who have a

family history of a genetic disorder and to people in certain ethnic groups with an

increased risk of specific genetic conditions.

3. Prognostic testing of diagnosed disease, to predict natural disease course, e.g., aggressiveness, recurrence, risk of death. This type of testing uses gene expression of

affected tissue to predict the course of disease, e.g., testing breast cancer tissue with

Oncotype DX

4. Genetic variants that alter response to treatment or to an environmental factor

a. Constitutional (germline) testing to detect genetic variants that alter risk of treatment response, adverse events, drug metabolism, drug effectiveness, etc., e.g.,

cytochrome p450 testing (also referred to as pharmacogenomics).

b. Tissue-specific or tumor testing: to detect mutations that predict response to a certain type of treatment (e.g., ALK mutation in non-small-cell lung cancer to

predict response to crizotinib)

c. Genetic mutations that adversely affect response to exposures in the environment that are ordinarily tolerated, such as G6PD deficiency, genetic disorders of immune

function, and aminoacidopathies.

Genetic counseling

The interpretation of the results of genetic tests and the understanding of risk factors can be very

difficult and complex. Therefore, most or all genetic testing for heritable conditions should be

preceded by genetic counseling so that the patient understands whether genetic testing should be

performed, or, if it is performed, what the potential impact of the information could be on the

patient and on his or her family.

Limitations of genetic testing

The testing methods may not detect all of the mutations that may occur in a gene

Genetic testing may identify variants of unknown clinical significance

Genetic testing may not necessarily determine the clinical outcome

Different genes can cause the same disease (genetic heterogeneity)

A mutation in a gene may cause different phenotypes (phenotypic heterogeneity)

Some disease-causing genes may not be identified as of yet

Genetic testing is subject to laboratory error

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V. DEFINITIONS TOP

ANALYTIC VALIDITY of a genetic test defines its ability to accurately and reliably measure the

genotype of interest.

ARRAY COMPARATIVE GENOMIC HYBRIDIZATION (also CMA, Chromosomal Microarray Analysis,

Microarray-based comparative genomic hybridization, array CGH, a-CGH, aCGH, or Virtual

Karyotype) is a technique to detect genomic copy number variations at a higher resolution level than

chromosome-based comparative genomic hybridization (CGH).

CHROMOSOME is one of the threadlike “packages” of genes and other DNA in the nucleus of a cell.

COPY-NUMBER VARIATIONS are alterations of the DNA of a genome that results in the cell having an

abnormal number of copies of one or more sections of the DNA. CNVs correspond to relatively large

regions of the genome that have been deleted (fewer than the normal number) or amplified (more than

the normal number) on certain chromosomes. For example, the chromosome that normally has

sections in order as A-B-C-D might instead have sections A-B-C-C-D (a duplication of "C") or A-B-D

(a deletion of "C").

CLINICAL VALIDITY of a genetic test defines its ability to detect or predict the associated disorder

(phenotype).

DIRECT-TO-CONSUMER GENETIC TESTING refers to genetic tests that are marketed directly to

consumers via television, print advertisements, or the Internet. This form of testing, which is also

known as at-home genetic testing, provides access to a person’s genetic information without

necessarily involving a doctor or insurance company in the process.

DNA a large nucleic acid molecule, found principally in the chromosomes of the nucleus of a cell,

that is the carrier of genetic information.

FIRST-DEGREE RELATIVE refers to a parent, sibling or child.

GENE is the basic unit of heredity, made of DNA, the code for a specific protein.

GENOTYPE is the specific genetic makeup of an individual, usually in the form of DNA.

KARYOTYPE is the chromosomal complement of an individual, including the number of

chromosomes and any abnormalities

MICROARRAY is a tool for analyzing gene expression that consists of a small membrane or glass slide containing samples of many genes arranged in a regular pattern. Each spot on an array is associated with a

particular gene. Each color in an array represents either healthy (control) or diseased (sample) tissue.

Depending on the type of array used, the location and intensity of a color will indicate whether the gene, or

mutation, is present in either the control and/or sample DNA. It will also provide an estimate of the

expression level of the gene(s) in the sample and control DNA.

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MITOCHONDRIA are intracellular organelles that are responsible for energy production and cellular

respiration.

MITOCHONDRIAL DISEASE refers to one of hundreds of congenital illnesses that result from

mutations in mitochondrial DNA. As a result, the mitochondria are unable to completely burn food

and oxygen in order to generate energy.

MUTATION is a permanent structural alteration in DNA.

PHENOTYPE IS the physical characteristics of an organism or the presence of a disease that may or

may not be genetic.

RNA is a chemical similar to a single strand of DNA. RNA delivers DNA’s genetic message to the

cytoplasm of a cell where proteins are made.

SECOND-DEGREE RELATIVE refers to an aunt, uncle, niece, nephew, or grandparent.

SUBTELOMERIC is below the telomere, the end of a chromosome.

THIRD-DEGREE RELATIVE refers to a great aunt/uncle, first cousin or great grandmother/grandfather.

VARIABLE EXPRESSION REFERS to variation in the manner in which a trait is manifested. When

there is variable expressivity, the trait may vary in clinical expression from mild to severe.

VI. BENEFIT VARIATIONS TOP

The existence of this medical policy does not mean that this service is a covered benefit under

the member's contract. Benefit determinations should be based in all cases on the applicable

contract language. Medical policies do not constitute a description of benefits. A member’s

individual or group customer benefits govern which services are covered, which are excluded,

and which are subject to benefit limits and which require preauthorization. Members and

providers should consult the member’s benefit information or contact Capital for benefit

information.

VII. DISCLAIMER TOP

Capital’s medical policies are developed to assist in administering a member’s benefits, do not constitute medical

advice and are subject to change. Treating providers are solely responsible for medical advice and treatment of

members. Members should discuss any medical policy related to their coverage or condition with their provider and

consult their benefit information to determine if the service is covered. If there is a discrepancy between this medical

policy and a member’s benefit information, the benefit information will govern. Capital considers the information

contained in this medical policy to be proprietary and it may only be disseminated as permitted by law.

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VIII. CODING INFORMATION TOP

Note: This list of codes may not be all-inclusive, and codes are subject to change at any time. The identification of a code in this section does not denote coverage as coverage is determined by the terms

of member benefit information. In addition, not all covered services are eligible for separate

reimbursement.

Covered when medically necessary:

Effective in 2013, if the specific analyte is listed in codes 81200-81355 or 81400-81408, that

CPT code would be reported. If the specific analyte is not listed in the more specific CPT

codes, unlisted code 81479 would be reported.

Current Procedural Terminology (CPT) copyrighted by American Medical Association. All Rights Reserved.

Diagnosis coding would depend on the condition for which the testing is being performed, if the

test is being performed as screening or carrier testing, and any family history of the condition.

*If applicable, please see Medicare LCD or NCD for additional covered diagnoses.

IX. REFERENCES TOP

1. Available online at: http://www.ncbi.nlm.nih.gov/sites/GeneTests/ Accessed November 6,

2013.

2. Available online at: http://www.nhmrc.gov.au/guidelines/publications/e99. Accessed

November 6, 2013.

3. Teutsch SM, Bradley LA, Palomaki GE et al. The evaluation of genomic applications in

practice and prevention (EGAPP) initiative: methods of the EGAPP Working Group.

Genet Med 2009; 11(1):3-14.

Other Sources

Novitas Solutions. Local Coverage Determination (LCD) L34796 Biomarkers for Oncology.

Effective 7/24/14. Assessed June 20, 2014.

Novitas Solutions. Local Coverage Determination (LCD) L33640 Biomarkers Overview.

Effective 12/5/13. Assessed June 25, 2014.

http://www.ncbi.nlm.nih.gov/sites/GeneTests/http://www.nhmrc.gov.au/guidelines/publications/e99http://www.novitas-solutions.com/webcenter/faces/oracle/webcenter/page/scopedMD/sad60252a_5537_4c5d_9350_ca405e36e159/Page128.jspx?wc.contextURL=%2Fspaces%2FMedicareJL&wc.originURL=%2Fspaces%2FMedicareJL%2Fpage%2Fpagebyid&contentId=00081277&_afrLoop=499336768241000#%40%3F_afrLoop%3D499336768241000%26wc.contextURL%3D%252Fspaces%252FMedicareJL%26wc.originURL%3D%252Fspaces%252FMedicareJL%252Fpage%252Fpagebyid%26contentId%3D00081277%26_adf.ctrl-state%3D104pm9zq50_61

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Centers for Medicare and Medicaid Services (CMS) National Coverage Determination (NCD) 190.3.

Cytogenetic Studies. Effective 7/16/1998. CMS [Website]: http://www.cms.hhs.gov.

Accessed June 25, 2014.

X. POLICY HISTORY TOP

MP- 2.326 CAC 5/24/14 New policy adopting BCBSA with additional CBC statements.

Guidelines provided for genetic testing when no specific policy is in place. MP

2.232 Genetic Testing for Inheritable Disease retired. The following statements

were extracted from that policy and placed in the new policy.

Information on at home or direct to consumer testing

Information regarding once per lifetime limit. Now silent on karyotyping (i.e. chromosome analysis)

APPENDIX 1 APPROACH TO DETERMINING CLINICAL UTILITY FOR GENETIC TESTING

Direct Evidence If direct evidence is available on the impact of testing on outcomes, this evidence takes precedence. Examples of direct evidence would be:

• Trial comparing outcomes with use of the test versus outcomes without use of the test • Associational study of genetic testing with outcomes

Indirect Evidence When direct evidence is not available, indirect evidence should be evaluated. Indirect evidence is evidence that addresses one or more components of a chain of evidence, but does not itself connect the intervention with the outcome. An example of indirect evidence is the accuracy of the genetic test for diagnosing the clinical condition, ie, clinical sensitivity and specificity. If improved accuracy leads to improved diagnosis of the disorder, and if more accurate diagnosis leads to management changes that improve outcomes, then clinical utility has been established. Many of these disorders are rare, and high-quality evidence on the efficacy of treatment for the disorder is often lacking. This is particularly true for aspects of management such as increased surveillance for complications, ancillary treatments (physical therapy, occupational therapy, etc.), and referrals to specialists. When evidence on outcomes is lacking, a consideration may be given as to whether these aspects of care are considered standard-of-care for that disorder, especially when they are part of guidelines by authoritative bodies.

http://www.cms.hhs.gov/

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There are a number of factors that influence the strength of indirect evidence that is needed to determine whether health outcomes are improved. None of these factors are by themselves determinative of whether genetic testing should be performed, but they may be important determinants of the potential clinical utility of testing. Some of these considerations are as follows:

I. Factors impacting the strength of indirect evidence for diagnostic testing Disease Characteristics

Is life expectancy reduced with this disorder?

What is the level of physical and/or psychosocial morbidity (disability) associated with the disorder? o Severe morbidity/disability o Moderate morbidity/disability o Minor or no morbidity/disability

Impact of genetic test on diagnosis

Can genetic testing confirm the suspected diagnosis?

Can the diagnosis be confirmed by alternate methods without genetic testing?

o Disorder is defined by the presence of genetic mutation o Genetic test is one of several factors contributing to diagnosis o Unable to make diagnosis without genetic test in some patients

Can genetic testing rule out the disorder?

Can genetic testing eliminate the need for further clinical work-up?

o Is this a disorder in which the diagnosis can be difficult, and the patient may be subjected to long and complicated work-ups?

Impact of genetic test on management

Does confirmation of diagnosis by genetic testing lead to improved outcomes? o Initiation of effective treatment o Discontinue of ineffective treatment

Does confirmation of diagnosis by genetic testing lead to the Initiation of other management changes with uncertain impact on outcomes (referrals to specialists and/or ancillary care, initiate screening, etc.)

Does confirmation of diagnosis by genetic testing lead to initiation of other management changes that are considered “standard of care” treatment for disorder

Impact on Health Outcomes

Is there a definite improvement in health outcomes with genetic testing? o Eg, diagnosis cannot be made without genetic testing, and confirmation of diagnosis leads to

initiation of effective treatment

Is there a possible, but not definite, improvement in health outcomes with genetic testing?

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o Eg.diagnosis cannot be made without genetic testing, and confirmation of diagnosis leads to

management changes with uncertain impact on outcomes

Are there significant barriers to research, such as rarity of the disorder?

What is the impact of genetic testing on lifestyle factors? o Employment/occupational decision-

making

o Leisure activities

o Reproductive decision-maker

Appendix Table A – Factors influencing the strength of an indirect chain of evidence on

clinical utility – diagnostic testing

Disorder Disease Characteristics

Impact on diagnosis

Impact on Management

Impact on outcomes

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II. Factors impacting the strength of indirect evidence for risk assessment testing Disease Characteristics

Is life expectancy reduced with this disorder?

What is the level of physical and/or psychosocial morbidity (disability) associated with the disorder? o Severe morbidity/disability o Moderate morbidity/disability

o Minor or no morbidity/disability

Is there a pre-symptomatic phase during which a clinical diagnosis cannot be made? Impact of genetic test on defining risk of disease

Can genetic testing determine the risk of subsequent disease in at least a substantial proportion of the population tested?

Is there a known mutation in the family?

Is the penetrance of the genetic mutation known?

Are there other factors that impact the clinical expression of disease?

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Does confirmation of risk lead to interventions that are indicated for this condition in the pre-symptomatic phase

o Interventions that prevent or delay disease onset

o Surveillance for manifestations or complications of disease

Does confirmation of risk by a positive genetic test lead to the initiation of other management changes that may or may not lead to improved outcomes (referrals to specialists and/or ancillary care, initiate screening, etc.)

Does a negative test confirm a lack of risk for the disease, and does this lead to “turning off” interventions, such as surveillance, that would otherwise be performed?

Is it likely that knowledge of mutation status will lead to alterations in reproductive decision-making?


Is there a definite improvement in health outcomes with genetic testing? o Eg, risk assessment cannot be made without genetic testing, and confirmation of risk leads to

initiation of effective preventive interventions that delay onset of disease

Is there a possible, but not definite, improvement in health outcomes with genetic testing?

o Eg risk assessment cannot be made without genetic testing, and confirmation of risk leads to

management changes with uncertain impact on outcomes

Are there significant barriers to research, such as rarity of the disorder?

What is the impact of genetic testing on lifestyle factors?

o Employment/occupational decision-making



Appendix Table 2 – Factors influencing the strength of evidence for risk assessment testing.


Impact on defining risk


Impact on outcomes

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III. Factors influencing the strength of indirect evidence for prognosis testing

Disease Characteristics

• Is life expectancy reduced with this disorder? • What is the level of physical and/or psychosocial morbidity (disability) associated with the disorder?

o Severe morbidity/disability

o Moderate morbidity/disability


Impact of genetic test on prognosis

• Does the genetic test have an association with prognosis of disease? • Does genetic testing lead to an incremental improvement in prognosis above that which can be done

by usual testing?

• Does the genetic testing allow classification of patients into clinically credible prognostic groups? o Have these prognostic groups been defined clinically?


• Are different prognostic groups associated with different treatment interventions?

o Type of intervention

o Timing of intervention

• Has treatment according to risk category been demonstrated to improve outcomes? • Is treatment according to risk category considered standard of care for this disorder?


• Is there a definite improvement in health outcomes with genetic testing? o Eg, Reclassification by prognosis leads to change in management that is known to be effective for the condition.

• Is there a possible, but not definite, improvement in health outcomes with genetic testing?

o Eg Reclassification by prognosis leads to changes in management with uncertain impact on outcomes

• Are there significant barriers to research, such as rarity of the disorder? • What is the impact of testing on lifestyle factors?

o Employment/occupational decision-making



MEDICAL POLICY



Page 16

Appendix Table 3 – Factors influencing the strength of indirect evidence - prognostic testing


Impact on prognosis


Impact on outcomes

Sho

rten

ed L

E

Seve

re m

orb

idit

y/d

isab

ility

Mo

der

ate

mo

rbid

ity/

dis

abili

ty

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or

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dis

abili

ty

Mu

tati

on

ass

oci

ate

d w

ith

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gno

sis

Incr

emen

tal i

mp

rove

men

t ab

ove

clin

ical

mea

sure

s

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ntr

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tes

to a

bili

ty t

o m

ake

dia

gno

sis

Clin

ical

ly c

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ible

pro

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stic

gro

up

s

Init

iate

eff

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ve t

reat

men

t fo

r

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er

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isco

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effe

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iate

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anag

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tmen

t fo

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ite

imp

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d h

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oss

ible

imp

act

on

ou

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,

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rier

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res

earc

h

Imp

act

on

life

styl

e fa

cto

rs

IV. Factors influencing the strength of indirect evidence for genetic variants that alter response to

treatment Disease Characteristics • Is life expectancy reduced with this disorder? • What is the level of physical and/or psychosocial morbidity (disability) associated with the disorder?

o Severe morbidity/disability

o Moderate morbidity/disability


• Is there effective pharmacologic therapy for this disorder? Impact of genetic testing on assessing response to treatment

• Can genetic testing define variants that are associated with different pharmacokinetics of drug metabolism?

• Are these changes in drug metabolism clinically important?

o Variants have been associated with clinically significant differences in outcomes of treatment

• Are there genetic variants that are associated with increased risk for adverse effects?

Impact of genetic test on pharmacologic management • Does identification of genetic variants lead to changes in pharmacologic management?

o Initiation of alternate agents

o Discontinue of ineffective agents

o Changes in dosing

MEDICAL POLICY



Page 17


• Is there a definite improvement in health outcomes with genetic testing?

o Eg, identification of variants leads to initiation of medications that are known to be effective.

• Is there a possible, but not definite, improvement in health outcomes with genetic testing?

o Eg identification of variants leads to change in pharmacologic management with uncertain impact

on outcomes

• Are there significant barriers to research, such as rarity of the disorder?

Appendix Table 3 – Factors influencing the strength of indirect evidence – genetic variants

that alter response to treatment Disorder Disease Characteristics

Impact on response to treatment


Impact on outcomes

Sho

rten

ed L

E

Seve

re m

orb

idit

y/d

isab

ility

Mo

der

ate

mo

rbid

ity/

dis

abili

ty

M

ino

r o

r n

o m

orb

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y/d

isab

ility

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ctiv

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har

mac

oki

net

ics

ph

arm

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c th

erap

y

Def

ine

vari

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wit

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iffe

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ph

arm

aco

kin

etic

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nt

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aco

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cs a

re

clin

ical

ly im

po

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ad t

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iffe

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ian

ts w

ith

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ease

d r

isk

for

adve

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cts

Init

iati

on

of

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oss

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act

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,

dat

a la

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rier

s to

res

earc

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Appendix 2: Policies related to genetic testing.

Please note: Due to the rapid changes taking place in the genetic testing field this may not

be a complete list of all the CBC genetic testing policies. Please review the CBC policy

website for additional policies which may have been added since the effective date of this

policy.

MP-2.235 Assays of Genetic Expression in Tumor Tissue as a Technique to Determine

Prognosis in Patients with Breast Cancer

MP-2.242 Chromosomal Microarray (CMA) Analysis for the

Genetic Evaluation of Patients with Developmental Delay/Intellectual

Disability or Autism Spectrum Disorder

MP-2.234 Cytochrome p450 Genotyping

MP-2.050 Diagnostic Testing and Risk Assessment for Alzheimer’s Disease

(Biochemical and Genetic)

MEDICAL POLICY



Page 18

MP-2.244 DNA-Based Testing for Adolescent Idiopathic Scoliosis

MP-2.241 Epidermal Growth Factor Receptor (EGRF) Mutation Analysis for Patients

with Non-Small Cell Lung Cancer (NSCLC)

MP-7.006 First-Trimester Detection of Down Syndrome Using Fetal-Ultrasound

Markers Combined with Maternal Serum Assessment

MP-2.313 Gene Expression Testing to Predict Coronary Artery Disease

MP-2.323 General Approach to Evaluating the Utility of Genetic Panels

MP-2.251 Genetic Testing for Alpha-1 Antitrypsis Deficiency

MP-2.320 Genetic Testing for Alpha Thalassemia

MP-2.322 Genetic Testing for CHARGE Syndrome

MP-2.257 Genetic Testing for Duchenne and Becker Muscular Dystrophy

MP-2.321 Genetic Testing for Facioscpulohumeral Muscular Dystrophy

MP-2.246 Genetic Testing for Familial Cutaneous Malignant Melanoma

MP-2.308 Genetic Testing for Helicobacter Pylori Treatment

MP-2.312 Genetic Testing for Hereditary Hemochromatosis

MP-2.318 Genetic Testing for Hereditary Pancreatitis

MP-2.211 Genetic Testing for Inherited Breast and Ovarian Cancer

MP-2.253 Genetic Testing for Inherited Thrombophilia

MP-2.232 Genetic Testing for Inheritable Disease – to be retired 8/1/14

MP-2.310 Genetic Testing for Lipoprotein(a) Variant as a Decision Aid for Aspirin

Treatment

MP-2.233 Genetic Testing for Cardiac Ion Channelopathies (Formerly Genetic Testing

for Long QT Syndrome)

MP-5.013 Genetic Testing for Lynch Syndrome and Inherited Colon Cancer Syndromes

MP-2.319 Genetic Testing for Non-syndromic Hearing Loss

MP-2.248 Genetic Testing for Predisposition to Inherited Hypertrophic Cardiomyopathy

MP-2.255 Genetic Testing for PTEN Hamartoma Tumor Syndrome

MP-2.307 Genetic Testing for Tamoxifen Treatment

MP-2.306 Genetic Testing for Warfarin Dose

MP-2.311 Genotyping for 9p21 Single Nucleotide Polymorphism

MP-9.002 Immune Cell Function Assay

MP-2.210 In Vitro Chemoreistance and Chemosensitivity Assays

MP-2.309 KIF6 Genotyping for Predicting Cardiovascular Risk and/or Effectiveness of

Statin Therapy

MP-2.240 KRAS Mutation Analysis in Non Small Cell Lung Cancer (NSCLC)

MP-2.316 KRAS and BRAF Mutation Analysis in Metastatic Colon Cancer

MP-2.245 Microarray-Based Gene Expression Test for Cancers of Unknown Primary

MP-2.231 Morphometric Based Testing

MP-2.252 Multianalyte Assays with Algorithmic Analysis for the Evaluation and

Monitoring of Patients with Chronic Liver Disease

MP-2.254 Multianalyte Assays with Algorithmic (MAAA) Interpretation for Predicting

Risk of Type 2 Diabetes

MEDICAL POLICY



Page 19

MP-2.315 Multi-Gene Expression Assay for Predicting Colon Cancer Recurrence

MP- 2.249 Non-BRCA Breast Cancer Risk Assessment (OnceVue)

MP-2.247 NOTCH3 Genotyping for Diagnosis of CADASIL

MP-2.218 Pharmacogenomic and Metabolite Markers for Pts with Inflammatory Bowel

Disease Treated with Thiopurenes

MP-7.009 Preimplantation Genetic Testing

MP-2.256 Sequencing-Based Tests to Determine Trisomy 21 for Maternal Plasma DNA

MP-2.228 Serologic Diagnosis of Celiac Disease

MP-2.237 Systems Pathology for Predicting Risk of Recurrence in Prostate Cancer

MP-2.212 Tumor Markers and Tumor Related Molecular Testing

MP-2.250 Use of Common Genetic Variants to Predict Risk of Non-Familial Breast

Cancer

MP-2.324 Whole Exome Sequencing

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Health care benefit programs issued or administered by Capital BlueCross and/or its subsidiaries, Capital Advantage Insurance

Company®, Capital Advantage Assurance Company® and Keystone Health Plan® Central. Independent licensees of the BlueCross

BlueShield Association. Communications issued by Capital BlueCross in its capacity as administrator of programs and provider

relations for all companies.

mp-2.236 general approach to genetic testing · 2015. 5. 13. · medical policy policy title...

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