1. Helena Kemp Consultant Chemical Pathologist North Bristol NHS Trust
Concepts of Screening
Helena Kemp
Consultant Chemical Pathologist
North Bristol NHS Trust

2. 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

3. 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 direct
preventative action, amongst persons who have
not sought medical attention on account of
symptoms of that disorder. ‘

4. Principles of Screening Wilson and Jungner 1968
The condition is an important health problem
Its natural history is well understood
It is recognisable at an early stage
Treatment is better at an early stage
A suitable test exists
An acceptable test exists
Adequate facilities exist to cope with abnormalities detected
Screening is done at repeated intervals when the onset is insidious
The chance of harm is less than the chance of benefit
The cost is balanced against benefit

5. 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

6. 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

7. NSC Consumer groups HTA Population Screening Panel Advisory groups egg
Child Health Subgroup
and antenatal Subgroup
DH Policy Research
Programme
NSC
Royal Colleges
Other sources of
evidence e.g. MRC
Professional organisations
NHS managing
clinical innovations
group

8. 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’.

9. UK National Screening Committee revised criteria 2003 www. nsc. nhs
UK National Screening Committee revised criteria
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

10. NSC screening policies www.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

11. UK National Screening Committee Programmes Director, Sir Muir Gray
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 Syndrome
Screening
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
Diabetic
Retinopathy
Cervical
Breast
Bowel Cancer
Fetal Anomaly
Ultrasound
screening
Newborn Hearing Screening

12. 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

13. Screening Algorithm newborn CF screening

14. Assessing the performance of a screening test
Affected
Unaffected
Total
Test positive a b
a + b
Test negative c d
c + d
a + c
b + d n
Sensitivity = a / a + c
Specificity = d/ b + d
Positive predictive value = a/ a + b
Negative predictive value = d/ c + d

15. 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 value
The 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 including
justification for further tests and resources

16. Roc curve analysis

17. Screening programmes Systematic Breast cancer, newborn bloodspot
Opportunistic
STI
Targeted
Tay sachs ashkenasi jewish population

18. Newborn bloodspot screening
Pre-analytical
Obtaining informed consent Child, family, midwife
Taking the sample Midwife
Sending sample to lab Midwife
Analytical
Primary screening test Screening lab
Second tier tests Screening & referral labs
Interpretation and reporting Screening lab consultant
Post analytical
Checking coverage Child Health Department
Reporting normal results to parents Health visitor
Confirmation of positives Specialist paediatrician
Genetic counselling Genetic Nurse/midwife

19. Integration of screening programmes

20. 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

21. The UK Newborn Screening Programme Centre (est. 2002)
UKNSPC
Set process standards
coverage, timeliness,
communication of results,
referral standards
Patient Registers
Policy for parental consent
Information
for parents and
professionals
Training
Policy for blood
spots retention
Informatics

22. Process standards Newborn bloodspot screening
Timely sample collection
Timely sample dispatch
Completeness of coverage
Enhanced tracking abilities
Timely notification of unscreened babies
Timely processing of positive screening samples

23. 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).

24. Parent Information

25. Education resources for HCP
Internet resources
Programme specific training material
Educational programs
PEGASUS
NSC commissioned professional training for informed choice
Other Resources
Cards for Midwives

27. A model of screening -MCADD
Evidence base
Pilot study
Assessment against NSC criteria
Ministerial announcement Feb 2007
Implementation

28. The balance of harm vs benefit
Benefits
Harms
Early 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

29. Extended newborn screening Newborn Screening with Tandem MS - New South Wales, Australia B Wilcken et al NEJM 2003; 348:
4 years experience
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

30. Effect of Expanded Newborn screening for biochemical genetic disorders on child outcomes and parental stress Waisbren et al JAMA
Prospective study of expanded screening
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

31. Results 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
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

32. 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 on
parents and current communication practices in newborn screening
Hewlett & Waisbren JIMD :

33. Useful resources www.nelh.nhs.uk/screening www.nsc.nhs.uk
Downs screening
Newborn screening
Sickle cell and thalassaemia