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
Warwick UniversityWarwick University
Warwick UniversityWarwick University
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.
Key Milestones in the Development of OSCARKey Milestones in the
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
Key Milestones in the Development of OSCARKey Milestones in the
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.
Key Milestones in the Development of OSCARKey Milestones in the
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