Transcript Document

The promises of genomic screening: building a
governance infrastructure
Lund,
Sweden
Genetics &
Democracy
Martina Cornel, MD, PhD and Carla van El, PhD
Community Genetics, Dept Clinical Genetics
Quality of Care
5th October 2009
EMGO Institute for Health and Care Research
Screening:
Definition US Commission on Chronic Illness 1951:
The presumptive identification of unrecognized disease or
defect by the application of tests, examinations or other
procedures which can be applied rapidly. Screening tests
sort out apparently well persons who probably have a
disease from those who probably do not. A screening test
is not intended to be diagnostic. Persons with positive or
suspicious findings must be referred to their physicians
for diagnosis and necessary treatment.
Neonatal screening (heelprick)
Neonatal screening NL 2006-2007
•
Biotinidase deficiency
•
Cystische fibrosis (conditional; pilot 2008)
•
Galactosemia
•
Glutaric aciduria type I
•
HMG-CoA-lyase deficiency
•
Holocarboxylase synthase deficiency
•
Homocystinuria
•
Isovaleric acidemia
•
Long-chain hydroxyacyl CoA dehydrogenase
deficiency
•
Maple syrup urine disease
•
MCAD deficiency
mental retardation or
•
3-methylcrotonyl-CoA carboxylase deficiency
sudden death
•
Sickle cell disease
•
Tyrosinemia type I
•
Very-long-chain acylCoA dehydrogenase deficiency
2006
• PKU
• Congenital
hypothyroidism
• Congenital Adrenal
Hyperplasia
Medication or
diet to avoid
Why more diseases?
• More treatment available
– Early detection: less health damage
• More tests available
– MS/MS
• Many more promises: governance needed?
Sources of presentation:
• Health Council of the Netherlands. Screening:
between hope and hype. The Hague: Health
Council of the Netherlands, 2008; publication no.
2008/05E. Available from www.gr.nl.
• Grosse SD, Rogowski WH, Ross LF, Cornel MC,
Dondorp WJ, Khoury MJ. Population Screening for
Genetic Disorders in the 21st Century: Evidence,
Economics and Ethics. Public Health Genomics,
Epub.
Screening: between hope and hype
• the rate at which useful new screening
opportunities become available is not as rapid as
reports in the media might sometimes indicate.
• cultural, social and economic factors contribute to
a situation in which various types of screening
(including self-testing kits) are placed on the
market without any proper investigation having
been conducted to ascertain whether the benefits
for those affected outweigh the disadvantages
that always also exist.
www.gr.nl Screening between hope and hype. Presentation of report.
Definition
Screening involves the clinical and laboratory
examination of individuals who exhibit no
health problems with the aim of detecting
disease, predisposition to disease, or risk
factors that can increase the risk of
disease.
(Health Council of the Netherlands, 2008)
Note: “systematic offer” not in this definition
Social developments relevant for screening
• Health care moving from a government-regulated
health care sector to one which is driven to a
greater or lesser extent by market forces.
• Blurring distinction between collective prevention
and individual client-focused care.
– Clinical genetic family testing vs cascade
screening for FH
• Need for reassurance: people increasingly
receptive to anything that promises to eliminate
risk.
What does this mean for the government?
• A fresh approach is needed to encourage sensible
screening and to protect individuals against the
risks of unsound screening.
• Extending regulations??????? Not..most suitable
• Independent body… nat screening committee UK
• Establish a quality-mark for responsible screening,
based on scientific assessments of new
developments and aimed at promoting responsible
provision and responsible choices.
www.gr.nl Screening between hope and hype.
Presentation of report
www.gr.nl, Screening: between hope and hype, p 34
New technological possibilities
– Attunement between parties
Achterbergh et al. Health Policy 2007; 83: 277-286.
Screening:
• Presymptomatic
(no symptoms or complaints yet)
• Offer of health care
• Systematic offer
(all newborns or all women aged 50-75)
• Sometimes voluntary, seldom “mandatory”
• Often low risk population; similar to self tests
Neonatal screening NL
Available from: www.gr.nl
Neonatal screening NL: the committee
Neonatal screening NL: disease categories
• Considerable, irreparable damage can be
prevented (category 1)
– Add 14 diseases (biotinidase deficiency,
galactosemia, glutaric
aciduria type I, HMG-CoA lyase deficiency, holocarboxylase synthase
deficiency, homocystinuria, isovaleric acidemia, longchain hydroxyacylCoA dehydrogenase deficiency, maple syrup urine disease, MCAD
deficiency, 3-methylcrotonyl-CoA carboxylase deficiency, sickle cell
disease, tyrosinemia type I and very-long-chain acyl-CoA
dehydrogenase deficiency).
• Less substantial or insufficient evidence of
prevention of damage to health (category 2)
– Consider adding cystic fibrosis if better test becomes
available (improve specificity)
• No prevention of damage to health (category 3)
Screening criteria: W&J still apply!
• When to screen?
– Wilson en Jungner WHO 1968.
– A variety of sets of criteria derived from W&J
• Important public health problem (prevalence & severity)
• Is treatment available? Does early treatment help?
• Course of disease known; frequency known
• Good test (high sensitivitity; high specificity, high positive
predictive value)
• Uniform treatment protocol; knowing whom to treat
• Etc
Balancing pros and cons
1. Treatment available? Effective? Available for all
and for ever? Affordable?
2. Good test available?
• False positives
• Specificity (1-FP)
• False negatives
• Sensitivity (1-FN)
• Positive predictive value
3. Unintended side effects
• Mild phenotypes
• Carriers identified
Disease
→
Present
Absent
Test
Result↓
Positive
Negative
A
B
C
D
Screening criteria
(Grosse et al, Public Health Genomics)
• Evidence
– Early treatment leads to less mortality, morbidity, loss of
weight, days in hospital, pain, suffering, better QoL
• Economics
– Limited health care resources; cost per QALY under limit
• Ethics
– More pros (longer and healthier life) than cons (false
positives; mild cases; incidental findings)
What’s new? (Grosse; Tab 1)
•Quality of the overall screening program
monitored & assured
•Informed choice
•Equity in access
•Acceptability
Balancing pros and cons; Grosse et al.
•Technical issues of analytic and clinical
validity
Clinical utility:
•Scientific evidence – medical benefits &
harms
•Balance of economic costs & health
outcomes
•Ethical issues
Evidence
High quality observational evidence is
lacking for most disorders-> little
agreement between countries.
• Systematical assessment EGAPP
genetic tests: BRCA/Lynch
• Systematical assessment neonatal
screening:
1. CDC review 2004;
2. ACMG: clinical experts criticized by
advocates of EBM
Evidence
Systematical assessment (neonatal)
screening:
NL: Health Council:
• 2005: endorsed 14 additional disorders for
which acceptable test was available & early
treatment could prevent irreparable damage
• 2007: self test kits
• 2008: new approaches to evaluate tests to
avoid coverage of unsound screening tests ..
promote.. worthwhile approaches.
Evidence
Discussion: CF & CAH
The number of deaths prevented
through screening for either disorder
is difficult to quantify.
Deaths before diagnosis? Case-control
studies needed.
Evidence not convincing: population wide
screening for HFE mutations
Economic criteria
• Cost-effectiveness analysis
Net cost per death prevented or lifeyear gained
• Cost-utility analysis
combine information on mortality &
morbidity; cost per QALY
Limited in the ability to inform policy
decisions-> alternative methods need to
be explored
Economic criteria
• Cost saving? Averted cost>>
intervention cost?
• If not, good value for money?
1. NICE-UK:GBP 30.000 per QALY Nat
Health Service
2. €80.000 per QALY NL
3. USA: wide range of cost per QALY
Ethics
• Informed consent; mandatory neonatal
screening; parental consent or awareness
required; opt out;
• Promotion of informed participation
• NL: always voluntary, but parents not
informed of the option to decline
screening
• France: written consent for DNA (99,8%)
Ethics: informed consent
• USA: Voluntary screening for disorders
for which the evidence of benefit to the
child is less compelling?
Conclusion Grosse et al.
• Genetic screening policies have typically
been determined by technological
capability, advocacy, and medical opinion
rather than through a rigorous, objective,
evidence-based review process.
• Ethical and economic evidence alongside
scientific evidence.
• Transparent and open to stakeholder
engagement.
• BUT WHO & HOW?
The role of the government
(Health Council 2008)
• Duty of care: ensure worthwhile screening
– National population screening programme:
provide facility itself
– Available in basic healthcare package
– Reproductive screening: special position:
provide worthwhile options and guarantee both
quality and informed decision making
• Duty of protection against unsound screening
– Guard citizens against health damage from
risky or unsound forms of screening
Protection
(Health Council 2008)
• Population Screening Act: unique in the world
• Some forms of screening must undergo
independent quality test before Minister issues
licence:
– Population screening using ionising radiation
– Population screening for cancer
– Population screening for serious diseases or
abnormalities for which no treatment or
prevention exists
Protection – 2
(Health Council 2008)
• Self testing: European IVD directive
• Purpose clear? Works as it is supposed to?
Does not endanger health or safety of patients
and users?
• Risk classes: high, medium, low
• High & medium: must be assessed by notified
body
• Low: assessed by the manufacturer
• NL: Marketing channel regulations: High risk only
sold via professional intermediary
Protection – 3 - Bottlenecks
(Health Council 2008)
• Population screening act: arbitrary categories for
licencing, inflexible. Why are some intensively
evaluated while others are not?
– Cardiovascular disease vs. cancer
• Enforcement: prosecution only for parties who
carry out screening, not those who offer it and
carry it out over the German border
• Do it yourself testing kits easily obtained from
Internet or pharmacist
• Ban=restriction on freedom?
Protection – 4 – Self regulation?
• Quality control
• Accreditation/certification
• Standards
• Recognition of competence
www.epbs.net/brussels/
An active approach is needed
(Health Council 2008)
• Responsible screening should be available and
accessible
– Strong proactive engagement government
• Protect citizens against risk of unsound screening
– Quality mark: information, education,
exposure, trust
• Positive evaluation->public provision
• No significant benefits, but no major drawbacks
either-> leave to market forces
• Negative evaluation->independent information; public
exposure