processes of technology diffusion and implementation around prenatal screening in europe jane...

Processes of

Technology Diffusion

and Implementation

Around Prenatal

Screening in Europe

Jane Sandall, King’s College, London IHT at the HTAi, Rome

21 – 22 June 2005

RCM

Social and Organisational Implications of One Stop First Trimester Prenatal Screening

Jane SandallJane Sandall

Gillian Lewando-HundtGillian Lewando-Hundt

Bob HeymanBob Heyman

Kevin SpencerKevin Spencer

Clare WilliamsClare Williams

Laura PitsonLaura Pitson

Maria TsouroufliMaria Tsouroufli

Rachel GrellierRachel Grellier

King’s College, King’s College,

Warwick UniversityWarwick University

City UniversityCity University

Harold Wood NHS Harold Wood NHS TrustTrust

King’s CollegeKing’s College

King’s CollegeKing’s College



Downs Syndrome in Europe

Analysis of data from 24 EUROCAT registries, Analysis of data from 24 EUROCAT registries, covering 8.3 million births 1980-99.covering 8.3 million births 1980-99.Since 1980, the proportion of births to Since 1980, the proportion of births to mothers of 35 years of age and over has mothers of 35 years of age and over has risen.risen.By 1995-99, the proportion of “older”mothers By 1995-99, the proportion of “older”mothers varied between regions from 10% to 25%, and varied between regions from 10% to 25%, and the total prevalence (including terminations the total prevalence (including terminations of pregnancy) of Down Syndrome varied from of pregnancy) of Down Syndrome varied from 1 to 3 per 1,000 births.1 to 3 per 1,000 births.The proportion of cases of Down Syndrome The proportion of cases of Down Syndrome whichwhichwere prenatally diagnosed followed by were prenatally diagnosed followed by termination of pregnancy in 1995-99 varied termination of pregnancy in 1995-99 varied from 0% - 77%.from 0% - 77%.

Eurocat Activity Report 2001-3Eurocat Activity Report 2001-3

European Screening PolicyCountry 1st 2nd PND TOP

Croatia Funding not stated

NT+Blood Triple >35, father >45

yes

Denmark 2005

NT+Blood ?Triple High risk, FH, >35

yes

France

All NT Free

Bio High risk, FH, >38 Free

yes

Germany NT Pay

Triple >35 Free

yes

Ireland No On request Pay

On request Pay

no

Netherlands NT Free > 36

Triple Free over 36

High risk, FH, >36 Free

yes

Norway USS > 38 Free

>38, FH Free

yes

Sweden None >35, FH Free

yes

Switzerland All Blood + NT Free

Blood NTD High risk, >35, FH Free

yes

UK 2004 All Blood + NT

Blood High risk, >35, FH Free

yes

Prenatal Screening Policies in Europe, Eurocat 2005Prenatal Screening Policies in Europe, Eurocat 2005

UK National Policy‘‘The aim of screening for fetal The aim of screening for fetal anomalies is to identify specific anomalies is to identify specific

structural malformations. This allows structural malformations. This allows the parents to plan appropriate care the parents to plan appropriate care

during pregnancy and childbirth or for during pregnancy and childbirth or for the parents to be offered other the parents to be offered other

reproductive choices…. reproductive choices…. The woman’s right to accept or decline the test

should be made clear’

Antenatal Care: Routine care for the healthy Antenatal Care: Routine care for the healthy pregnant woman, NICE October 2003pregnant woman, NICE October 2003

Prenatal Screening Prenatal Screening Practice in UKPractice in UK

HeadHead Upper limbsUpper limbs

Lower limbsLower limbs

Increased NTIncreased NT

Broader Issues Whether/how women make selective Whether/how women make selective

use of technologies use of technologies Inequalities of accessInequalities of access Broader ethical and public policy Broader ethical and public policy

implicationsimplications Women’s understanding of risk Women’s understanding of risk

languagelanguage Routinisation and informed decision-Routinisation and informed decision-

makingmaking Raising anxiety Raising anxiety

New Issues Raised by 1st Trimester Prenatal Screening

Offered to all women rather than those at riskOffered to all women rather than those at riskRequires redesign of care to ensure informed consentRequires redesign of care to ensure informed consentCreates uncertainty rather than certaintyCreates uncertainty rather than certaintyBenefits Benefits – – Avoids PND in older women unless necessary thus Avoids PND in older women unless necessary thus

reduce risk of fetal lossreduce risk of fetal loss- Increases equity of access when offered to all women- Increases equity of access when offered to all womenShould provide an informed choice to all womenShould provide an informed choice to all womenHarmsHarms- 5% women will screen high risk of whom 5% true 5% women will screen high risk of whom 5% true

positive thus risk of raised anxiety and fetal loss positive thus risk of raised anxiety and fetal loss with PNDwith PND

- Routine offer may reduce ability to opt outRoutine offer may reduce ability to opt out- Negative message to society re DSNegative message to society re DS

Prenatal Screening Technology Assessment

in UKTrialsTrialsReviewsReviewsImplementation and Implementation and

organisational studiesorganisational studiesAcceptabilityAcceptabilityEconomicEconomic

Project Aims to Improve Understanding Of:

• Impact of new screening technologies Impact of new screening technologies on social management of pregnancy, on social management of pregnancy, service delivery and professional rolesservice delivery and professional roles

Participants broader responses to new Participants broader responses to new reproductive technologies, and views reproductive technologies, and views about routinisation of screeningabout routinisation of screening

Perceptions of self, the fetus, and of Perceptions of self, the fetus, and of management of reproductive riskmanagement of reproductive risk

Lay and professional understanding of Lay and professional understanding of complex information, and influences on complex information, and influences on decision-makingdecision-making

Design

Antenatal and postnatal survey of 993 Antenatal and postnatal survey of 993 and 656 women respectivelyand 656 women respectively

Observation of 45 clinic sessions in Observation of 45 clinic sessions in hospital and community hospital and community

Interviews with 24 health professionals Interviews with 24 health professionals and a cohort of 27 women and some and a cohort of 27 women and some partners on a range of screening partners on a range of screening pathwayspathways

Analysis of 90 audio-taped Analysis of 90 audio-taped consultationsconsultations

Research SettingTwo sitesTwo sites

InnovativeInnovative one stop one stop – one of few NHS – one of few NHS sites in UKsites in UK

First trimester screening at a one-stop First trimester screening at a one-stop clinic at 12-13 weeks, NT ultrasound clinic at 12-13 weeks, NT ultrasound scan and blood test and result within scan and blood test and result within 1 hour1 hour

Standard two stopStandard two stopSecond trimester screening at 15-20 Second trimester screening at 15-20

weeks, result back within 1 weekweeks, result back within 1 week

Spencer et al (2003)BJOG,110:281-6.

OSCAR - A 1st Trimester One Stop Clinic for Assessment of

Risk for fetal anomalies

OSCAR - A 1st Trimester One Stop Clinic for Assessment of

Risk for fetal anomalies One stop clinics have developed over the past One stop clinics have developed over the past

decade in several clinical areas ranging from decade in several clinical areas ranging from breast cancer screening, menopausal breast cancer screening, menopausal clinics,oncology assessment, cardiovascular risk clinics,oncology assessment, cardiovascular risk clinics and one stop surgical clinics.clinics and one stop surgical clinics.

These services all have in common the integration These services all have in common the integration of a range of clinical and diagnostic services that of a range of clinical and diagnostic services that allow for a better use of clinical time and improved allow for a better use of clinical time and improved diagnostic efficiency.diagnostic efficiency.

They aim to maximise patient satisfaction by They aim to maximise patient satisfaction by reducing the number of patient visits; minimising reducing the number of patient visits; minimising patient travel costs, anxiety and stresspatient travel costs, anxiety and stress

Point-of-Care screening for Chromosomal Anomalies in the First Trimester of Pregnancy. Point-of-Care screening for Chromosomal Anomalies in the First Trimester of Pregnancy. Spencer K, Clin Chem 2002; 48: 403-404Spencer K, Clin Chem 2002; 48: 403-404

Evidence & Innovations Leading to Development of

OSCAR

Evidence & Innovations Leading to Development of

OSCAR Ultrasound markers of chromosomal Ultrasound markers of chromosomal

anomalies - fetal nuchal translucency anomalies - fetal nuchal translucency thickness at 11-14 weeks.thickness at 11-14 weeks.

Maternal serum Biochemical markers Maternal serum Biochemical markers of chromosomal anomalies - free b-of chromosomal anomalies - free b-hCG & PAPP-A at 10-14 weeks.hCG & PAPP-A at 10-14 weeks.

Development of new rapid assay Development of new rapid assay technology for biochemical marker technology for biochemical marker measurement leading to Point of Care measurement leading to Point of Care testing.testing.

Kryptor AnalyserNobel Prize winning chemistry

Kryptor AnalyserNobel Prize winning chemistry

Small bench top analyser - clinic basedSmall bench top analyser - clinic based Rapid assay times (19 mins)Rapid assay times (19 mins) Kinetic reading - leading to automatic rediluting Kinetic reading - leading to automatic rediluting

of high samples within 4 minutesof high samples within 4 minutes PrecisePrecise - cv less than 3% between day - cv less than 3% between day Continuous sample access Continuous sample access - stat capability- stat capability Small sample (<50ul) and reagent (<150ul) Small sample (<50ul) and reagent (<150ul)

volumes.volumes. User friendlyUser friendly Other manufacturers now developing POC Other manufacturers now developing POC

systems for Prenatal Screening.systems for Prenatal Screening.

Jean-Marie Lehn; Nobel Laureate in Chemistry 1987Jean-Marie Lehn; Nobel Laureate in Chemistry 1987

Point of Care 1st Trimester Platforms

KryptorKryptor

Delfia ExpressDelfia Express

Key Milestones in the Development of OSCARKey Milestones in the Development of OSCAR

1987 - Jean-Marie Lehn becomes Nobel 1987 - Jean-Marie Lehn becomes Nobel Laureate in Chemistry for the development Laureate in Chemistry for the development of the caged Kryptate molecules used in of the caged Kryptate molecules used in the Kryptor TRACE technology.the Kryptor TRACE technology.

1988 – CIS (French Company) part fund the 1988 – CIS (French Company) part fund the Down’s Screening Research program of Dr Down’s Screening Research program of Dr Spencer.Spencer.

1988 – CIS licences the Kryptate 1988 – CIS licences the Kryptate technology with the view to developing a technology with the view to developing a new immunoassay analyser system.new immunoassay analyser system.

1991 – Free 1991 – Free ββ-hCG identified as a Second -hCG identified as a Second Trimester Down’s marker by Dr SpencerTrimester Down’s marker by Dr Spencer

Key Milestones in the Development of OSCARKey Milestones in the

Development of OSCAR 1991- PAPP-A identified as a potential First 1991- PAPP-A identified as a potential First

Trimester Down’s marker by Dr Brambati.Trimester Down’s marker by Dr Brambati. 1991 - BHR Hospitals introduce early (12wk) 1991 - BHR Hospitals introduce early (12wk)

dating scan with early GP referall.dating scan with early GP referall. 1992 – Nuchal Translucency identified as a 1992 – Nuchal Translucency identified as a

potential First Trimester Down’s marker by potential First Trimester Down’s marker by Kypros Nicolaides.Kypros Nicolaides.

1992 – Free 1992 – Free ββ-hCG identiifed as a potential -hCG identiifed as a potential First Trimester Down’s marker by Dr First Trimester Down’s marker by Dr Spencer.Spencer.

1993 – Early prototype and concept of 1993 – Early prototype and concept of Kryptor first discussed.Kryptor first discussed.


Development of OSCAR 1994 – First studies indicating clinical 1994 – First studies indicating clinical

effectiveness of PAPP-A & Free effectiveness of PAPP-A & Free ββ-hCG as a -hCG as a First Trimester marker – Dr Spencer.First Trimester marker – Dr Spencer.

1995 – Fetal Medicine Foundation (FMF) set 1995 – Fetal Medicine Foundation (FMF) set up by Kypros Nicolaides to promote training, up by Kypros Nicolaides to promote training, certification and audit of NT measurement.certification and audit of NT measurement.

1995 – OSCAR concept conceived by Dr 1995 – OSCAR concept conceived by Dr Spencer.Spencer.

1995 – Kryptor development program begun 1995 – Kryptor development program begun for Free for Free ββ-hCG and PAPP-A-hCG and PAPP-A

1995/6 – First studies combing NT with Free 1995/6 – First studies combing NT with Free ββ-hCG – Nicolaides & Spencer-hCG – Nicolaides & Spencer


Development of OSCAR 1996 – FMF multicentre prospective NT study 1996 – FMF multicentre prospective NT study

starts – BHR a participating centre.starts – BHR a participating centre. 1996/7 - First retrospective clinical studies 1996/7 - First retrospective clinical studies

performed using Kryptor combing biochemistry performed using Kryptor combing biochemistry & NT in BHR.& NT in BHR.

1997 – Business case presented to BHR Trust to 1997 – Business case presented to BHR Trust to set up OSCAR clinic.set up OSCAR clinic.

1998 – Approval for OSCAR, live 11998 – Approval for OSCAR, live 1stst June 1998. June 1998. 1999 – Second OSCAR centre set up in Harley 1999 – Second OSCAR centre set up in Harley

Street.Street. 1999 – CIS announces a stop to the Kryptor 1999 – CIS announces a stop to the Kryptor

development program unless a buyer is found development program unless a buyer is found for its Immunodiagnostics business.for its Immunodiagnostics business.


Development of OSCAR 2000 – Brahms of Germany takes over the

marketing of Kryptor. CIS R&D facility makes management buy out enabling production and development of Kryptor to continue in a new company (Cezanne) part owned by Brahms.

2004 – PerkinElmer launches a ME2 Kryptor platform aimed at Point of Care testing for Down’s screening.

2005 – Over 250 Kryptor systems placed World Wide, 70% involved in Prenatal Screening.

2005 – Some 20 OSCAR clinics established World Wide.

NTNT BIOCHEMBIOCHEM SOFTWARESOFTWARE

STANDARDSTANDARD STANDARDSTANDARD STANDARDSTANDARD

TRAININGTRAINING APPROVED APPROVED SYSTEMSSYSTEMS

USES FMF USES FMF ALGORITHMALGORITHM

ASSESSMENTASSESSMENT EQAEQA APPROVED APPROVED SYSTEMSSYSTEMS

CERTIFICATIONCERTIFICATION LAB LAB CERTIFICATIONCERTIFICATION

LINKED TO LINKED TO CERTIFICATIONCERTIFICATION

ONGOING ONGOING AUDITAUDIT

ONGOING ONGOING AUDITAUDIT

AUDIT & AUDIT & UPDATEUPDATE

FMF QUALITY SYSTEM

Processes of technology innovation

Limits to evidenceLimits to evidence

Impact of professionalsImpact of professionals

Networks and networkingNetworks and networking

Communities of practiceCommunities of practice

Funding systemFunding system

Consumer agencyConsumer agency

What was the attitude of doctors and midwives to you having a screening test for

Down’s syndrome?

0

10

20

30

40

50

60

70

Enc neutral disc

Stand profOne stop prof

N=867N=867P=0.000P=0.000

Professional influenceProfessional influence

What do women value?

Most women in both sites said fast results and knowing results early were very important

75% of all women were prepared to pay for earlier screening in a future pregnancy

79% of women said that combined screening at about 12 weeks was the their option

55% of women had decided whether or not to have screening before being offered any

Technology, Routinisation and Informed decision-making

19% women said screening not fully discussed

DS as a condition and post screening options rarely discussed

27 % women in IHT site never made up mind and went along with offer

45% women in IHT site offered as part of routine care and it was assumed that they would accept

67% women in IHT site reported professionals encouraging

Pathways from innovation to national policy

Funding counts

Gaps in technology assessment

Importance of professional attitudes in the clinic

Influence of user demand

Investigating unintended consequences at implementation phase

Ignore organisation and delivery of IHT at your peril!

ImplicationsImplications

DisseminationOn Being At Higher Risk: A Qualitative Study Of Prenatal Screening For Chromosomal Anomalies, Heyman,B. Lewando-Hundt,G. Sandall,J. Spencer,K. Williams,C. under review Social Science and Medicine.

Women as ‘moral pioneers’?: experiences of first trimester antenatal screening’, Williams, C. Sandall, J. Lewando Hundt, G. Grellier, R. Heyman, B, Spencer, K. in press Social Science and Medicine

Constraints on informed choice in a one-stop first trimester prenatal screening for Down’s syndrome: a cross-sectional survey of women’s experiences, Sandall,J. Pitson,L. Williams, C. Lewando Hundt, G., Heyman, B. Spencer, K. under review BJOG

Wellcome People Production Award, Social, ethical and cultural impacts of genetic prenatal screening technologies on experience and personhood: synthesising Biochemistry and Ultrasound technologies with Live Performance, Visual and Aural Media.

http://www.kcl.ac.uk/nmvc/research/project/moreinfo.php?id=11&the_group=1

processes of technology diffusion and implementation around prenatal screening in europe jane...

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