Post on 22-Jan-2016
Concepts of Screening
Helena KempConsultant Chemical Pathologist
North Bristol NHS Trust
Outline of talk
• The definition & principles of screening• National screening policy• The screening ‘test’• The screening ‘programme’• Quality management• Public & professional education• A model of screening - MCADD• The balance of harm vs benefit
Definition of Screening
‘The systematic application of a test or enquiry to
identify individuals at risk of a specific disorder
to warrant further investigation or directpreventative action, amongst persons who
havenot sought medical attention on account ofsymptoms of that disorder. ‘
Principles of Screening Wilson and Jungner 1968
1. The condition is an important health problem 2. Its natural history is well understood 3. It is recognisable at an early stage 4. Treatment is better at an early stage 5. A suitable test exists 6. An acceptable test exists 7. Adequate facilities exist to cope with abnormalities
detected 8. Screening is done at repeated intervals when the onset
is insidious 9. The chance of harm is less than the chance of benefit 10. The cost is balanced against benefit
Screening in the UK
Improving Screening: A Public Health Task for the Nineties Public Health Network – March 1994
- Variations in policy, including no policy- Variations in practice- Absence of standards- Absence of performance measurement- Patchy training- Poor patient information- No clear lines of accountability
The UK National Screening Committee
• Established 1996
• The UK National Screening Committee advises Ministers, the devolved National Assemblies and the Scottish Parliament on:
– The case for implementing new population screening programmes.
– Screening technologies– The case for continuing, modifying or withdrawing
existing population screening programmes
• Set up practical mechanisms to oversee the introduction & implementation of a new programme in the NHS & monitor effectiveness and quality assurance
NSC
HTA Population Screening Panel
DH Policy Research Programme
Other sources of evidence e.g. MRC
Advisory groups egg Child Health Subgroup and antenatal Subgroup
Consumer groups
Royal Colleges
Professional organisations
NHS managing clinical innovationsgroup
Revised definition of screening
‘Screening is a public health service in which members of a defined population, who do not necessarily perceive they are at risk of, or are already affected by a disease or its complications, are asked a question or offered a test, to identify those individuals who are more likely to be helped than harmed by further tests or treatment to reduce the risk of a disease or its complications’.
UK National Screening Committee revised criteria 2003
www.nsc.nhs.uk/pdfs/criteria.pdf
• Appraise the viability, effectiveness and appropriateness of a screening test
• Additional criteria:
– Requirements of screening programmes which include mutation analysis
– Evidence base i.e. Randomised Controlled Trial data to indicate that screening programme effectively reduces mortality or morbidity
– Quality management of screening programmes
– Provision of information for informed choice to participate
NSC screening policieswww.nsc.co.uk
• Nationally managed programme– e.g. Antenatal Downs screening, Newborn CF, Breast Cancer
• Planned National programme– e.g National Chlamydia Screening Programme
• Screening - with reservations – e.g. Prostate Cancer (Prostate Cancer Risk Management
Programme)
• Under review– e.g. abdominal aortic aneurysm men over 65 years
• Not recommended – e.g. antenatal CF, CAH, bladder cancer
NSC Organisational Structure
UK National Screening Committee
Programmes Director, Sir Muir Gray
Fetal, Maternal & Child Health subgroup (FMCH) Vascular Screening
Cancer Screening Programmes
Down‘s SyndromeScreening
Sickle Cell and Thalassaemia Screening
Infectious Diseases; HIV, Hepatitis B, Syphilis, Rubella
Newborn Blood spot screening
Cystic Fibrosis screening
Newborn and 6-8 week Infant Physical Examinations
Vascular Diseases Risk Management
DiabeticRetinopathy
CervicalScreening
BreastScreening
Bowel CancerScreening
Fetal Anomaly Ultrasoundscreening
Newborn Hearing Screening
The screening test
• An enquiry e.g. ethnicity• An examination e.g. 6-8 wk physical
examination• An investigative procedure e.g. fetal anomaly
scanning • A single analytical test e.g. phenylalanine PKU• Multiple markers
• Multivariate risk calculation • Multi protocol
Screening Algorithm newborn CF screening
Assessing the performance of a screening test
Affected Unaffected Total
Test positive a b a + b
Test negative
c d c + d
Total a + c b + d n
Sensitivity = a / a + c
Specificity = d/ b + d
Positive predictive value = a/ a + bNegative predictive value = d/ c + d
Performance of a screening test
• Detection rate (sensitivity)The proportion of affected individuals with a positive result
• False positive rate (specificity = 1-FPR)The proportion of unaffected individuals with a positive result
• Positive predictive valueThe chance that those with a positive test result are affected
• Performance will depend on cut-off levels chosen
• Cut–off chosen will be influenced by many factors includingjustification for further tests and resources
Roc curve analysis
Screening programmes
• Systematic – Breast cancer, newborn bloodspot
• Opportunistic– STI
• Targeted– Tay sachs ashkenasi jewish population
Newborn bloodspot screening
Pre-analyticalObtaining informed consent Child, family, midwifeTaking the sample MidwifeSending sample to lab Midwife
AnalyticalPrimary screening test Screening labSecond tier tests Screening & referral labsInterpretation and reporting Screening lab consultant
Post analyticalChecking coverage Child Health DepartmentReporting normal results to parents Health visitorConfirmation of positives Specialist paediatricianGenetic counselling Genetic Nurse/midwife
Integration of screening programmes
Principles of quality management for screening
Nuffield Institute of Health March 2000
• A clear coherent framework of objectives, standards & guidance
• A culture of learning, not blame• A partnership with staff and users• Continuous quality improvement• Clear management structures• Effective & efficient performance measurement• Adequate systems & resources• Bridging the expectation gap
The UK Newborn Screening Programme Centre (est. 2002)
UKNSPC
Set process standardscoverage, timeliness, communication of results,referral standards
Patient Registers
Policy for parental consent
Informationfor parents and professionals
Training
Policy for blood spots retention
Informatics
Process standards Newborn bloodspot screening
1. Timely sample collection
2. Timely sample dispatch3. Completeness of
coverage4. Enhanced tracking
abilities5. Timely notification of
unscreened babies6. Timely processing of
positive screening samples
Laboratory quality standards newborn sickle cell screening
• Accreditation by an appropriate body (e.g. CPA).
• Consultant led service with defined lines of responsibility for all laboratory aspects of the service.
• HPLC & IEF methodology with a different technique for confirmation from initial screen.
• Appropriate internal quality control undertaken and documented
• Compulsory participation in an accredited EQA appropriate for newborn screening (NEQAS scheme)
• Provision of information on screening performance to monitoring groups (NSC, NPC).
• Workload should exceed 25,000 specimens per year (ideally 50,000).
Parent Information
Education resources for HCP
• Internet resources – www.screening.nhs.uk/cpd – Programme specific training material
• Educational programs – PEGASUS – NSC commissioned professional training for informed
choice
• Other Resources – Cards for Midwives
A model of screening -MCADD
• Evidence base
• Pilot study
• Assessment against NSC criteria
• Ministerial announcement Feb 2007
• Implementation
The balance of harm vs benefit
Benefits HarmsEarly detection allowing earlier effective treatment
False positive and false negative test results
Identification of risk allowing preventative measures
Invasive potentially dangerous tests
Greater awareness among individuals of their own health
Over detection of symptom less disease may lead to unnecessary treatment
Control of disease at population level
Psychological distress due to unfavourable test results
Identification of carrier status allows informed family planning
Genetic screening may impact on relatives raising questions re disclosure of information
Cost effective means of disease control
Extended newborn screening Newborn Screening with Tandem MS - New South Wales,
Australia B Wilcken et al NEJM 2003; 348:2304-12
• 4 years experience 1998-2002
• 362,000 newborns screened
• 31 disorders detected, 57 babies (15.7 per 100,000 screened)• Urea cycle 7• Amino acid disorders 9• Organic acid disorders 12• Fatty acid oxidation disorders 29
– SCAD 5– MCAD 17– VLCAD 3– Carnitine defects 4
Effect of Expanded Newborn screening for biochemical genetic disorders on child outcomes
and parental stressWaisbren et al JAMA 2003 290 2564-2572
• Prospective study of expanded screening 1999-2002
• Participants – 50 affected families – identified by NS– 33 affected families - clinically diagnosed– 94 false positive children– 81 screen normal children
• Main outcome measures– Child’s health and development – Parental Stress index
Results
1. Cases identified by newborn screening vs clinical diagnosis– 28% NS vs 55% clinically identified required hospitalisation– 1 NS vs 8 clinically identified children severe learning difficulties– Mothers in screened group reported lower stress on PSI than
mothers in clinically identified group
2. False positive group vs normal screening result• 21% children with false positive results vs 10% hospitalised• Mothers in false positive group attained higher scores on PSI• Mothers in false positive group attained higher scores on Parent
child dysfunction subscale
False positives in expanded newborn screening
• Prevalence of true positives– 1 in 2400 infants screened (0.04%)
• Prevalence of false positives– 1 in 300 infants screened (0.33%)
• 8 false positives for every true positive
• Approx 13,000 false positives/year
A review of the psychosocial effects of false positive results onparents and current communication practices in newborn screeningHewlett & Waisbren JIMD 2006 29:677-682
Useful resources
• www.nelh.nhs.uk/screening• www.nsc.nhs.uk• www.screening.nhs.uk
• Downs screening – www.nehl.nhs.uk/screening/dssp/home.htm
• Newborn screening – www.newbornscreening-bloodspot.org.uk
• Sickle cell and thalassaemia – www.kcl-phs.org.uk/haemscreening