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