Transcript Growth Hormone Replacement Therapy

Growth Hormone Replacement
Therapy: Interpreting Guidelines for
Clinical Practice
Pinchas Cohen, MD
Dean, USC Davis School,
Adjunct Professor of Pediatric Endocrinology
Growth Hormone Replacement Therapy:
Interpreting Guidelines for Clinical Practice
• History of growth hormone (GH) consensus statements &
clinical guidelines
• Value of GH consensus statements & clinical guidelines
• Review of key GH statements & clinical guidelines
• Future of guidelines and statements on GH therapy
History of Growth Hormone
Why Consensus Statements
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Needs from the community
Emerging standard of care
New studies and data change practices
New controlled trials
New FDA approved indications
Unpublished clinical experience
Unpublished registry data
Geographical variability in clinical practice
Changing payer climate
Litigious environment
Who is Served by Consensus Statements
The pediatric endocrine community:
•FDA approvals were broad and lacked specific guidance
•De facto, these guidelines establish a standard of care
•Protect doctors who follow guidelines from frivolous lawsuits
•Establishing the basis for dialogue with payers
Patients:
•Providing detailed guidelines on the approach to diagnosis,
treatment, and monitoring of growth disorders
•Establish best unbiased proven practices for effective treatment
The First GH Consensus Statement - 1990
Issues and concerns:
• Industry sponsored
• Driven by a single drug company
• No involvement of learned societies
A New Era in Consensus Statements
1992 – Growth Hormone Research Society (GRS) founded:
• Developed a philosophy for support of the GH field
• Recognized need for unbiased guidelines
• Developed independence from commercial influence
• Established a tradition of consensus workshops
• Worked with other societies
GRS Consensus Statements 1998-2005
• Consensus guidelines for the diagnosis and treatment of adults with
growth hormone deficiency: summary statement of the Growth Hormone
Research Society workshop on adult growth hormone deficiency.
J Clin Endocrinol Metab. 1998;83:379–381.
• Consensus guidelines for the diagnosis and treatment of growth hormone
(GH) deficiency in childhood and adolescence: summary statement of the
GH Research Society. J Clin Endocrinol Metab. 2000;85:3990–3993.
• Critical evaluation of the safety of recombinant human growth
hormone administration: statement from the Growth Hormone Research
Society. J Clin Endocrinol Metab. 86:2001;1868–1870.
• Biochemical assessment and long-term monitoring in patients with
acromegaly: statement from a joint consensus conference of the Growth
Hormone Research Society and The Pituitary Society. J Clin Endocrinol
Metab. 2004;89:3099–3102.
• Consensus statement on the management of the GH-treated adolescent in the
transition to adult care. Eur J Endocrinol.2005;152:165–170.
GRS Consensus Statements 2007-2013
• Management of the child born small for gestational age through to adulthood:
a consensus statement of the International Societies of Pediatric Endocrinology and the
Growth Hormone Research Society. J Clin Endocrinol Metab.2007;92:804–810.
• Consensus guidelines for the diagnosis and treatment of adults with GH deficiency II: a
statement of the GH Research Society in association with ESPE and LWPES. Eur J
Endocrinol.2007;157:695–700.
• Consensus statement on the diagnosis and treatment of children with idiopathic short
stature: a summary of the Growth Hormone Research Society, the LWPES and ESPE
workshop. J Clin Endocrinol Metab.2008;93:4210–4217.
• Statement by the Growth Hormone Research Society on the GH/IGF-I axis in extending
health span. J Gerontol A Biol Sci Med Sci.2009;64A:1039–1044.
• Consensus statement on the standardization and evaluation of growth hormone and
insulin-like growth factor assays. Clin Chem.201;57:555–559.
• Growth Hormone Research Society workshop summary: consensus guidelines
for recombinant human growth hormone therapy in Prader-Willi syndrome. J Clin
Endocrinol Metab.2013 Mar 29. [Epub ahead of print]
Goals of Consensus Workshops
1. Ultimate goal: to serve patients and doctors
2. Aim: to set a standard in a field fraught with controversy
3. Final product: consensus statement
4. Consumers of the statement: clinicians, payers, regulators
5. Address the key issues outlined in the questions posed
6. Define an INTERNATIONAL perspective
7. Not to focus on important items outside the defined scope
Structure of Consensus Workshops
• Based on the NIH consensus model
• Evidence review of published (and unpublished) data on the
topic in the first part of the workshop
• A set of questions addressing unresolved issues in the
diagnosis and management of the condition are circulated
• Succinct review lectures and focused presentations of relevant
topics were given by invited experts
• Breakout sessions discuss specific topics
• Discussions are reviewed and summarized
• Consensus document is written and reviewed in real time
Representation in Consensus Workshops
Example – ISS consensus
• 32 experts
• 15 countries
• 8 professional societies
• 6 industry observers
Most of the funding came in the form of grants from
participating organizations, such as GRS, LWPES, and
ESPE as well as small unrestricted educational grants
from several supporting industry members of GRS.
ISS = idiopathic short stature.
Sample Workshop Format
Review
Review
Definition
& Epidem.
Ethics &
Therapy
Review
Review
Review
Review
Consensus
drafting
Day 3
Diagnostic
work up
GH
treatment
Review
Review
Writing up
Writing up
Day 1
Day 2
Workshop structure
• Breakout group discussion
and review of key issues
• A writing group transcribes
discussion summaries into a
consensus draft
• Critical review by all
participants in a plenary
forum
• Participants vote and reach a
majority decision on each
section
• They are sent a polished draft
for additional comments and
give signed approval to the
final revision
Limited GH Guidelines
from PES (last one 2003)
GH is indicated in children with a clinical
picture of GHD who fail GH stimulation tests.
In addition, a trial of GH therapy is warranted
in children who may have atypical GHD with
unexplained short stature and the following
clinical findings:
Height >2.25 SD below the mean for age or >2
SD below the midparental height percentile
Growth velocity <25th percentile for bone age
Bone age >2 SD below the mean for age
Low serum IGF-1 and/or IGFBP-3
Other clinical features suggestive of GHD
2013 update coming?
GHD = growth hormone deficiency.
More from PES
More from PES
Use of AIs in boys with ISS, GHD, or CDGP may increase adult
height modestly; however, data are lacking, and there is no
information identifying which children are likely to benefit most.
We urge physicians to exercise caution in the use of these agents
outside of controlled clinical trials.
AI = aromatase inhibitors; CDGP = constitutional
delay in growth and puberty.
Pediatrics.2008;121:e975–e983.
Use of GH for ISS in the US
Patients (#)
10,000
?
ISS CONSENSUS
FDA APPROVAL
5,000
HINTZ PAPER NEJM
1992
2002
YEAR
2012
A Backlash?
Normal at Any Cost:
Tall Girls, Short Boys,
and the Medical
Industry's Quest to
Manipulate Height.
Susan Cohen. 2009.
Consensus Statement on the
Diagnosis and Treatment of
Children with Idiopathic
Short Stature: A Summary of
the Growth Hormone Research
Society, the Lawson Wilkins
Pediatric Endocrine Society
and the European Society for
Paediatric Endocrinology
Workshop.
J Clin Endocrinol Metab.2008;
93:4210–4217.
Investigation of the GH Secretion
Consensus Statement on the Diagnosis and Treatment of Children with Idiopathic Short
Stature. J Clin Endocrinol Metab.2008;93:4210–4217.
• GHD must be excluded to make a diagnosis of ISS
• Majority: Short, with normal height velocity, no bone age
delay and a plasma IGF-I level above the mean does not
require GH testing
• Minority: GH testing irrespective of IGF-I levels
• The choice of GH stimuli is country-dependent, as is the
decision to prime with sex steroids
• Traditionally, a peak GH < 10 ng/mL = GHD, but new GH
standards and assay methodologies may require a
downward adjustment of the lower limit
• Assessing spontaneous GH secretion not indicated
Criteria for Treating Children with ISS
Consensus Statement on the Diagnosis and Treatment of Children with Idiopathic Short
Stature. J Clin Endocrinol Metab.2008;93:4210–4217.
• Auxological: FDA approved < -2.25 SDS (1.2 percentile)
• Expert opinions range from - 2 SDS to – 3 SDS
• Optimal age for initiating treatment is 5 years to early
puberty
• There are no accepted biochemical criteria for initiating
GH
• Psychological: weigh the degree of short stature and the
coping capacity of the child
Response to GH Treatment
• Successful 1st year response: delta height SDS > 0.3; a
HV increment >3 cm/year; HVSDS > +1
• Emerging tools: prediction modeling/specific charts
• Serial IGF-I to assess efficacy, safety and compliance,
and as tool for adjusting the GH dose
• No other biochemical tests are routinely recommended in
GH-treated ISS patients
• If after 1-2 years, plus higher doses of GH, growth rate is
still inadequate, GH should be stopped and alternative
therapies could be entertained
Female
Male
n=842
n=2318
16
14
12
10
8
6
4
2
0
2
3
4
5
6
7
8
9 10 11 12 13 14
Age at baseline
First-year height velocity (cm/yr)
First-year height velocity (cm/yr)
First-Year Growth Responses to Daily GH in ISS
16
14
12
10
8
6
4
2
0
2
Mean HV +1 SD
Mean HV
Mean HV –1 SD
Mean Pretreatment HV
3
4
5
6
7
8
9 10 11 12 13 14
Age at baseline
HV = height velocity.
Figure copyright © 2008, The Endocrine Society. Reproduced with permission.
First-year growth responses to daily GH expressed as HV at age of treatment onset (x-axis) in patients with GHD using data from the
Genentech National Cooperative Growth Study; Data given for mean, mean  1, and mean pretreatment HV.
Adapted from Bakker B et al. J Clin Endocrinol Metab. 2008;93(2):352-357.
GH Treatment Adjustment Strategies
Consensus Statement on the Diagnosis and Treatment of Children with Idiopathic Short
Stature. J Clin Endocrinol Metab.2008;93:4210–4217.
• Dosage is usually selected and adjusted by weight
• If the growth response is considered inadequate, the
dose may be increased
• There are no definitive data concerning the long-term
safety of doses higher than 70 mcg/kg/day in ISS
• IGF-I levels may be helpful in assessing compliance
and GH sensitivity; levels that are consistently elevated
(>2.5 SDS) should prompt consideration of GH dose
reduction
Duration of GH Treatment
Consensus Statement on the Diagnosis and Treatment of Children with Idiopathic Short
Stature. J Clin Endocrinol Metab.2008;93:4210–4217.
Two schools of thought:
1. Treatment should stop when near adult height is
achieved (HV < 2 cm/year, and/or BA > 16- boys / 14girls).
2. Therapy can be discontinued when height is in the
“normal” adult range (> – 2 SDS), or as in Australia, the
10th percentile or the 50th percentile
Stopping therapy is influenced by patient/family
satisfaction and cost-benefit analysis
BA = bone age.
Care of Turner Syndrome (Led from the NIH)
Care of the Child with SGA
Consensus Statement
• Diagnosis should be based on accurate
anthropometry at birth
• At-risk children: early neurodevelopment
evaluation and intervention
• Endocrine and metabolic disturbances are
infrequent
• 10% lack “catch-up” growth
• GH therapy can increase linear growth in
those lacking catch-up growth
• For severe growth retardation (-2.5 SD, 24 yr), start GH at 35-70 μg/kg/d
• SGA associated with coronary disease
and stroke later in life
• Presently, inadequate evidence to
recommend routine surveillance outside
normal clinical practice
SGA = small for gestational age.
Consensus Guidelines for Adult GHD &
Transition-Age Patients
• Appropriate patients should undergo repeat GH testing at
least one month after discontinuation of GH treatment
• In patients with CO GHD
– Before the age of 20 years, the need for
continuation of GH replacement should be
evaluated following completion of statural growth
– At approximately 25 years of age, a second reinvestigation can be considered in those with COisolated idiopathic GHD
• Repeat GH testing is not required in patients with
– Transcription factor mutations (eg, POU1F1 [Pit-1],
PROP-1, HESX-1, LHX-3, LHX-4)
– >3 pituitary hormone deficits
– Isolated GHD associated with identified mutation
(eg, GH-1, GHRH-R)
Ho KKY. Eur J Endocrinol. 2007;157(6):695–700.
The Latest Workshop: Prader-Willi
Syndrome (PWS)
•
Objective:
Compose recommendations for the use of rhGH in children and adult patients with PWS
Recommendations:
• Consideration of rhGH treatment should be made in patients with genetically confirmed PWS in
conjunction with dietary, environmental, and lifestyle interventions
– Cognitive impairment should not be a barrier to treatment
– Risk/benefit information should be part of informed consent
– GH Dose should be adjusted to maintain IGF-I levels within the normal range (<-2SDS)
Reviews on Consensus Statements and
Clinical Guidelines
The Actual Utility of Clinical Guidelines
• Leverage industry: (eg, the diagnostic companies now
provide better assays and express values as SDS)
• Dealing with rogue practices & off-label use of GH/IGF
• Feedback and citations (eg, ISS consensus cited > 50
times; safety consensus cited >30 times)
Future of Guidelines and Consensus
Statements
• GH safety, take-2 (2014)
• IGFD (2015)
• Emerging issues? (audience suggestions?)
A Managed Care View of Growth
Hormone Replacement Therapy:
Plan Perspectives
Michael Fine, MD
Senior Medical Director
Health Net of California
Woodland Hills, California
Can Managed Care afford health
care reform?
Can Managed Care afford not to
have reform?
Cumulative Increases in Health Insurance Premiums, Workers’
Contributions to Premiums, Inflation, and Workers’ Earnings, 1999-2011
Kaiser/HRET Survey of Employer-Sponsored Health Benefits,
1999-2011. Bureau of Labor Statistics, Consumer Price Index,
U.S. City Average of Annual Inflation (April to April), 19992011; Bureau of Labor Statistics, Seasonally Adjusted Data
from the Current Employment Statistics Survey, 1999-2011
(April to April).
Who is paying for healthcare?
Who is paying for
growth hormone?
Percent Distribution of National Health
Expenditures, by Type of Sponsor, 1987, 2000, 2010
68.2%
64.5%
State & Local
Other Private Revenues
Federal
Household
Private Business
55.1%
44.9%
35.5%
31.8%
Government
Private
1987 (Total = $519.1 billion)
Government
Private
2000 (Total = $1,377.2 billion)
Centers for Medicare and Medicaid Services, Office of the Actuary, National Health
Statistics Group at https://www.cms.gov/NationalHealthExpendData/ (see Historical;
NHE Web tables, Table 5).
Government Private
2010 (Total = $2,593.6 billion)
Percent Distribution of Source of Funds for Selected
Personal Health Care Services, 1970 and 2010
1970
2010
Hospital Care
1970
2010
Physician & Clinical
Services
Centers for Medicare and Medicaid Services, Office of the Actuary, National
Health Statistics Group at https://www.cms.gov/NationalHealthExpendData/
(see Historical; NHE Web tables, Tables 7, 8, 11, 12).
1970
2010
Retail Prescription Drugs
1970
2010
Nursing Care Facilities &
Continuing Care Retirement
Communities
Distribution of Health Coverage Costs as a
Percentage of Payroll for Employees with Access to
Coverage, 1999-2010
Kaiser Family Foundation calculations based on data from the National
Compensation Survey, 1999-2010, conducted by the Bureau of Labor Statistics.
Who will sign up for the
healthcare exchanges?
Percent of Total Health Care Spending
Concentration of Health Care Spending in the U.S.
Population, 2009
(≥$51,951) (≥$17,402) (≥$9,570)
(≥$6,343)
Kaiser Family Foundation calculations using data from U.S. Department of
Health and Human Services, Agency for Healthcare Research and Quality,
Medical Expenditure Panel Survey (MEPS), Household Component, 2009.
(≥$4,586)
(≥$851)
(<$851)
Is the management of growth
hormones a priority for managed
care organizations (MCOs)?
La Merie Top 30 Biologics for 2013.
Drug Cost Trends
• Drug overall cost trends = 2.6%
• Specialty drug cost trend = 17.1%
• Growth hormone class trend = 6.6%
Express Scripts. Drug Trend Report 2011.
Growth Deficiency
Express Scripts. Drug Trend Report 2011.
Growth Hormone Product Trends
• Despite a decrease in the use of growth hormone medications in 2011, drug
trend for the class still was up 6.6%, due to increased cost.
• Double-digit growth was seen in the cost of several older brands of growth
hormones.
• Large utilization increases for the newer somatropin formulations, Nutropin
AQ® NuSpin™ (approved in 2009) and Norditropin® FlexPro® (approved
in 2010), contributed to higher utilization trend in 2011.
• Cost for Norditropin FlexPro actually dropped considerably, however, and
cost for Nutropin AQ NuSpin rose only moderately.
• Cost trends for two biosimilar growth hormones, Omnitrope® and TevTropin®, were down significantly (by 21.6% and 13.8%, respectively).
Utilization of each, however, increased more than 100% in 2011.
Express Scripts. Drug Trend Report 2011.
MCO Management of Growth Hormone
• Benefit Design
• Utilization Management
• Cost Management
% of Plans
Increasing Co-Insurance but More Out-ofPocket Max
MOOP = maximum out-of-pocket.
EMD Serono Specialty Digest 2013.
Growth Hormone is Highly Managed
EMD Serono Specialty Digest 2013.
Preferred Growth Hormone Products are
Very Common
EMD Serono Specialty Digest 2013.
One Plan’s Approach
• All human growth hormone products are therapeutically
equivalent.
• The use of preferred brand growth hormones is
appropriate.
• Growth hormones are interchangeable and can be used
for any FDA-approved indication, even off-label.
• All growth hormone products require prior
authorization.
• Specialty pharmacy is mandatory.
• Continued authorization for treatment in children
requires demonstration of adequate growth response.
Approved Indications
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Growth hormone deficiency in children and adolescents
Growth hormone deficiency in adults
Idiopathic short stature syndrome
Small for gestational age
SHOX (short stature homeobox-containing gene) deficiency
Chronic renal failure in pre-transplantation children
Prader-Willi syndrome, Turner syndrome, Noonan syndrome
Therapy of infantile hypoglycemia
Central nervous system tumor treated with radiation
Short-bowel syndrome
Growth Hormone Deficiency in Children
• Two (2) pharmacologic provocation tests (insulin, clonidine, arginine, levodopa,
glucagon) with a result < 10 ng/mL
• Patients who do not meet stimulation test criteria < 10ng/mL on both tests or
whose stimulation tests are discordant can be approved for a 6 month trial of
growth hormone if the other criteria for growth hormone deficiency have been
met and both IGF-1 and IGFBP-3 levels are below the normal range for gender
and age
• Diagnosis by a pediatric endocrinologist
• The patient's baseline height must be > 2 standard deviations [SD] below the
mean forgender and age (which corresponds to < 2.3 percentile)
• Growth rate is such that the patient is unlikely to attain an adult height in the
normal range - 59 inches for girls and 63 inches or boys (ie, growth velocity
below the 25th percentile or, alternatively, in children aged <3 years, pretreatment
growth velocity < 7cm per year and for children aged 3 years and older growth
velocity < 4 cm per year measured accurately for at least one year)
Idiopathic Short Stature Syndrome
• The patient's baseline height must be > 2.25 standard deviations
[SD] below the mean for gender and age (which corresponds to
< 1.2 percentile)
• The epiphyses must be open
• Growth rate is such that the patient is unlikely to attain an adult
height in the normal range - 59 inches for girls and 63 inches for
boys (ie, growth velocity below the 25th percentile or,
alternatively, in children aged < 3 years, pretreatment growth
velocity < 7cm per year and for children aged 3 years and older
growth velocity < 4 cm per year measured accurately for at least
one year measured accurately for at least one year)
Small for Gestational Age
• Child was born small for gestational age, defined as
birth weight or length 2 or more standard deviations
below the mean for gestational age
• Child must be at least two years old
• The patient's baseline height must be > 2 standard
deviations [SD] below the mean for gender and age
(which corresponds to < 2.3 percentile)
Continuation Criteria for hGH RX in Children
• Increased growth rate by two cm over baseline in first
year or one cm over baseline in 6 months for those
patients undergoing a 6-month trial
• Continued growth rate exceeds 2.5 cm/year
• For treatment of growth hormone deficiency child's
height remains below median adult height (5'10"for
males, 5'5" for females) and mid-parental height
• For non-growth hormone deficiency treatment, the
child' height continues to be >2.25 standard deviations
below the normal adult height for gender (5' 3" for a
male, 4' 11” for a female)
Adults with Growth Hormone Deficiency
• Pharmacologic provocation tests (insulin, clonidine, arginine,
levodopa, glucagon) with a result <10 ng/ml with RIA
(Radioimmunoassay) or <2.5ng/ml with IRMA
(Immunoradiometric assay)
• Hypothalmic or pituitary disease
• Significant clinical symptoms related to growth hormone
deficiency such as fatigue, poor endurance, poor sense of well
being persist despite maximizing treatment of other hormonal
disorders, mood disorders, and medical illness
• Patient has multiple pituitary hormone deficiencies resulting
from structural hypothalamic/pituitary disease, radiation, defined
CNS pathology, cranial radiation, trauma, pituitary surgery, or
genetic defect affecting the GH axis with low IGF-1 and low
IGFBP-3
Growth Hormone Utilization Management
Challenges 2013
• Adolescents in transition
• Adults with growth hormone deficiency
• HIV wasting
Future Landscape
• The growth hormone class is stable, with no late-phase
medications in the pipeline.
• More patient access under the Affordable Care Act
• Increase utilization in transition and adult patients
• More utilization management especially concerning
discontinuation and dose adjustment
• Parity of drug benefits under the medical and pharmacy
benefits
• Value based pricing
• Accountable Care Organizations (ACOs)
• Biosimilars
Value-Based Payment Methodologies
Approach to payment to providers that includes
incentives for achieving identified quality standards
and cost management targets
Accountable Care Organization (ACO)
As defined by the Affordable Care Act (ACA), ACOs
are provider-based organizations (medical groups,
hospitals that employ physicians, integrated delivery
systems, physician- hospital organizations, and
independent practice associations) that take
responsibility for the health care needs of a defined
population, e.g., Medicare patients.
Challenges for Success of ACOs
• Misalignment of physician and hospital incentives
• Absence of value based payment methodologies
• Need for greater integration of physicians and hospitals
• Absence of sufficient competition in some areas
Practical Considerations for the Use of
Growth Hormone Replacement Therapy
in a Managed Care Environment
Clifford A. Bloch, MD
Pediatric Endocrine Associates, P.C.
Greenwood Village, Colorado
Clinical Professor of Pediatrics
University of Colorado School of Medicine
Short Stature: Why Should We Care?
• Many attempts to discredit us as endocrinologists
• “Short stature is a cosmetic issue.”
• “There are no psychosocial consequences of being
short.”
• “Use of growth hormone is unethical in today’s
environment in which healthcare resources are already
stretched.”
We Should Care Because:
• Short stature is a symptom that may be a marker of an
underlying disease.
• Failure to evaluate a child with short stature under
certain circumstances is a violation of the standard of
care.
• Failure to diagnose may result in an adverse outcome
for the child and expose the physician to potential
malpractice litigation.
We Should Care Because:
• The reason why most kids are referred is because the
parents and kids are concerned.
• There is nothing unethical about practicing
evidence-based medicine!
• Since we, as physicians, do not set or fix the price of
growth hormone (GH), we cannot be responsible for
stretching the scarce resources, as long as we follow
the “on label” indications for use.
Why Are Parents and Kids Concerned?
A.
B.
C.
D.
E.
Something is wrong with the child.
The child is being teased at school.
The child’s younger sibling is as tall or taller
The child feels inadequate in class.
The child is struggling to keep up with the other
kids in sports.
F. When a teenage boy answers the phone, the caller
mistakes him for his sister or mother.
G. All of the above.
Evaluation of a Short Child In an Office
Setting
• A 7 year-old girl is
referred for short
stature.
• Linear growth velocity
has been subnormal
for the past year
Evaluation of a Short Child In an Office
Setting
• A 7 year-old girl is referred for short stature.
• Linear growth velocity has been subnormal for the past
year
• Prenatal, natal and postnatal history are unremarkable
• Mid-parental height at 50th percentile
• Physical exam reveals a morphologically normal,
prepubertal female, with proportionate short stature
• Her dental age is delayed.
• Thyroid is normal
• Optic funduscopy and visual fields are normal
Evaluation of a Short Child In an Office
Setting
• Bone age is delayed by 1 ½ years
• Lab investigations: Blood is drawn in the office for a
screening evaluation. In compliance with the
recommendations of Medicaid and the American
Medical Association (AMA), only the necessary tests
are ordered.
Lab Investigations
1. CBC or Hgb + Hct?
2. ESR?
3. Electrolyte panel or creatinine?
4. CO2 content?
5. Biochemistry panel 22?
6. Calcium, phos, alk phos?
7. AST, ALT?
8. IgA, TTG IgA AB’s?
9. TSH or thyroid panel?
CBC = complete blood count, Hgb = hemoglobin blood, Hct = hematocrit,
ESR = erythrocyte sedimentation rate, CO2 = carbon dioxide, phos =
10. Karyotype?
phosphorus, alk phos = alkaline phosphatase, AST = aspartate
aminotransferase, ALT = alanine aminotransferase, IgA = immunoglobulin
11. IGF-1, IGFBP-3?
A, TTG = tissue transglutaminase, AB = antibody, TSH = thyroid
stimulating hormone, IGF-1 = insulin-like growth factor 1, IGFBP-3 =
insulin-like growth factor-binding protein 3.
Would you do a sed rate, and if so, what are
you looking for?
A. Yes, I am looking for possible JRA or
inflammatory bowel disease.
B. No, the child is asymptomatic and these
diseases are uncommon in this age group.
Would you do a sed rate, and if so, what are
you looking for?
A. Yes, I am looking for possible JRA or
inflammatory bowel disease.
B. No, the child is asymptomatic and these
diseases are uncommon in this age group.
Would you check full electrolyte panel,
including BUN, creatinine, Na, K, Cl, and CO2
content or would you just check creatinine?
A. Full electrolyte panel
B. Creatinine only, because RTA and Bartter
syndrome are unlikely to present at this age,
and there is no reason to suspect electrolyte
abnormalities in an asymptomatic 7-year-old.
Would you check a biochemistry-22 panel or
would you just cherry pick tests like Ca, Phos,
Alk phos, AST, ALT?
A. Biochemistry panel-22
B. Selected tests only
Would you check a biochemistry-22 panel or
would you just cherry pick tests like Ca, Phos,
Alk phos, AST, ALT?
A. Biochemistry panel-22
B. Selected tests only
Would you check IgA and TTG IgA AB’s in
this girl, who has no weight loss or steatorrhea?
A. Yes, this is a routine part of my screen in all
children with growth failure of any kind.
B. No, I only check these in children who are
symptomatic.
Would you check IgA and TTG IgA AB’s in
this girl, who has no weight loss or steatorrhea?
A. Yes, this is a routine part of my screen in all
children with growth failure of any kind.
B. No, I only check these in children who are
symptomatic.
Would you check a TSH with reflex free T4 or
thyroid panel [free T4 and TSH]?
A. TSH only, because this is what is
recommended by the AMA for screening for
hypothyroidism
B. Thyroid panel, because I am screening for
primary or central hypothyroidism
Would you check a karyotype in this girl?
A. Yes. All short girls ought to be karyotyped, as
short stature may be the only manifestation of
Turner syndrome.
B. No. Abrupt linear growth failure and a
delayed bone age point to an acquired cause
for growth failure.
Would you check a karyotype in this girl?
A. Yes. All short girls ought to be karyotyped, as
short stature may be the only manifestation of
Turner syndrome.
B. No. Abrupt linear growth failure and a
delayed bone age point to an acquired cause
for growth failure.
Office-Based Growth Hormone Testing
• Despite the controversy about the value of GH testing,
the repeatability of GH testing, the variation in assay
methodologies, etc., most 3rd party payers require
documentation of GH deficiency in the setting of a
high index of clinical suspicion.
• If GH testing is to be done in an office setting, it needs
to be done safely, using standardized tests.
• To be reimbursed for the drugs used for testing, the
medication needs to be administered parenterally.
What do you think of GH testing in an
office setting?
A. I do not do GH testing, because it is unreliable.
B. GH testing is too risky to be done in an office
setting.
C. GH testing is safe in an office setting with
glucagon and arginine as the pharmacologic
stimuli.
What do you think of GH testing in an
office setting?
A. I do not do GH testing, because it is unreliable.
B. GH testing is too risky to be done in an office
setting.
C. GH testing is safe in an office setting with
glucagon and arginine as the pharmacologic
stimuli.
Office-Based Growth Hormone Testing
• Since 2 tests are required to increase the positive
predictive value of the results, we choose glucagon,
followed by arginine.
• We reject insulin, because of its high risk.
• We reject clonidine and L-dopa, because they are oral
agents.
• We have a designated testing room, replete with,
supplies, an infusion pump for the arginine, O2,
suction, and a crash cart.
• Room includes a DVD player and TV.
Growth Hormone Authorization
• Results are collated and documented in a table.
• They are interpreted, and the diagnosis of GH
deficiency is made.
• This is followed by a 1 mcg cortrosyn [ACTH] stim
test in the office, and a hypothalamic-pituitary, focused
MRI scan, pre- and post contrast in an outpatient MRI
facility.
• [Sometimes the ACTH stim test is done at the same
time as the GH stim testing.]
ACTH = adrenocorticotropic hormone, MRI = magnetic resonance imaging.
Reimbursement for the Costs of GH Testing
•
•
•
•
•
Nursing time
IV supplies
IV pump
Heparin flush
Drugs
– Arginine
– Glucagon
- 96365 [1st hr] + 96366 [x4]
- Bundled into nursing charge
- E0781
- J1642
- J3490
- J1610
• Physician time - E&M code
E&M = evaluation and management.
Reimbursement for the Costs of ACTH Testing
•
•
•
•
Nursing time
IV supplies
Heparin flush
Drugs
– Cortrosyn
- 96365 [1st hr] + 96366 [x1]
- Bundled into nursing charge
- J1642
- J0833
• Physician time - E&M code
Should cranial MRI scans with contrast
and conscious sedation be done in an
outpatient facility?
A. No. They should always be done in an inpatient
facility where pediatric anesthesia is available.
B. They could be done in an outpatient facility as
long as there are facilities and staff available to
deal with complications.
Should cranial MRI scans with contrast
and conscious sedation be done in an
outpatient facility?
A. No. They should always be done in an inpatient
facility where pediatric anesthesia is available.
B. They could be done in an outpatient facility as
long as there are facilities and staff available to
deal with complications.
How do you choose the brand of GH?
A. I have a rotation of brands.
B. I only use a few brands of my choice.
C. I use the preferred brand that is on formulary for the
patient’s insurance carrier.
D. I let my nurse or MA choose the brand before
writing a prescription.
How do you choose the brand of GH?
A. I have a rotation of brands.
B. I only use a few brands of my choice.
C. I use the preferred brand that is on formulary for the
patient’s insurance carrier.
D. I let my nurse or MA choose the brand before
writing a prescription.
Authorization of GH Therapy
• The letter with the results and documentation of GH
deficiency and recommendations for GH therapy is
submitted to insurance for authorization.
• We complete a patient demographic form and make a
copy of the insurance card and submit them to a
company that performs a “Pharmacy Benefits
Investigation” [PBI].
• Within 24 hrs, we receive a report indicating which
brands of GH are preferred by the patient’s insurance
company and/or pharmacy benefits manager [PBM],
and the patient co-payments for each.
Commencement of GH Therapy
• The physician selects the brand of GH that is most
advantageous, financially, for the patient and his/her
family.
• A prescription is written and submitted with a
“Statement of Medical Necessity” [SMN] to the case
manager of GH company, requesting a “rapid start.”
• A limited supply of “free” drug is shipped to the
patient.
• Once drug is received, patient is instructed to call our
office to schedule GH teaching for their GH start.
Who does the teaching for the GH start?
A. We have the GH company or a nursing
agency send a nurse to do the teaching at the
patient’s home.
B. We have our own staff do the teaching at our
facility.
Who does the teaching for the GH start?
A. We have the GH company or a nursing
agency send a nurse to do the teaching at the
patient’s home.
B. We have our own staff do the teaching at our
facility.
Commencement of GH Therapy
• Patient and family receive teaching at our office,
provided by a medical assistant, with full discussion
about anticipated response and known side-effects
• Patient and family also meet with physician
• Follow-up is scheduled in 3 months
• Sometime in the 3 month interval, the family and our
office will hear from the insurance company about
approval or denial of therapy.
• Patient has the option of continuing with therapy at the
family’s own expense if coverage is denied by
insurance
GH therapy is denied, because “GH is not a
covered benefit.” How do you respond?
A. I write a letter of appeal and am willing to do a
“peer-to-peer” conference call
B. I tell the patient’s family that they will need to
apply for assistance or bear the costs of therapy
themselves
GH therapy is denied, because “GH is not a
covered benefit.” How do you respond?
A. I write a letter of appeal and am willing to do a
“peer-to-peer” conference call
B. I tell the patient’s family that they will need to
apply for assistance or bear the costs of therapy
themselves
Continued GH Therapy
• Unlike previous times, we do not typically write letters
of appeal if the reason for the denial is that GH therapy
is “not a covered benefit.”
• Only if GH therapy is a covered benefit for the
diagnosis that is submitted, and insurance issues a
denial, based upon erroneous interpretation of the
rationale for the diagnosis, do we write a letter of
appeal.
• Repeat SMN’s are submitted upon request by the PBM
or insurance, with updated information.
Continued GH Therapy
• Visits are scheduled every 3 months.
• Usual standards of care are followed, including
documentation and communication with the primary care
physician.
• Prescriptions are given to the patient/family, who are
expected to submit them to their pharmacy.
• It is the patient’s responsibility to notify us of any changes
in their insurance.
• If the insurance formulary changes, a new SMN is
completed by us and sent together with a new prescription.
• Patient returns for re-teaching regarding the new GH
delivery system.
Criteria for Discontinuation (D/C) of
GH Therapy
• Unless the patient requests to D/C therapy early or
there are financial issues, side effects, etc., GH therapy
is continued to near-final height.
• It is my practice to D/C therapy after we document a
linear growth velocity of <0.5 cm every 3 months over
2 successive visits, assuming good compliance with
therapy.
• We also document a near-mature/mature bone age.
• All GH deficient patients undergo repeat GH testing
after a washout period, following D/C of GH.
Do you perform repeat GH testing in children
with idiopathic, isolated GH deficiency upon
completion of growth?
A. Not usually
B. Only in selected cases, where the diagnosis of
GH deficiency was made in early childhood,
outside of the period of physiologic, prepubertal growth deceleration
C. Yes, in most or all children with idiopathic,
isolated GH deficiency
D. Never, because GH testing is a waste of time
Do you perform repeat GH testing in children
with idiopathic, isolated GH deficiency upon
completion of growth?
A. Not usually
B. Only in selected cases, where the diagnosis of
GH deficiency was made in early childhood,
outside of the period of physiologic, prepubertal growth deceleration
C. Yes, in most or all children with idiopathic,
isolated GH deficiency
D. Never, because GH testing is a waste of time
Panel Discussion
Is there any consensus on the use
of growth hormone in
inflammatory bowel disease?
If a patient is growth hormone
deficient by stimulation test, why
would you consider their height?
And why would you consider their
velocity of growth?
Why don’t you just treat them?
What should be the appropriate
trajectory for the reduction in the
price of growth hormone over
time?
How do we bill for physician time
when we do growth hormone
stimulation tests if we don’t see the
patient?
There are long-acting growth
hormones in early stage
development now that probably
will be available in a few years.
How will they be handled?