Original Paper Fetal Diagn Ther 2014;35:193–198 DOI: 10.1159/000356075
Received: July 12, 2013 Accepted after revision: October 1, 2013 Published online: November 13, 2013
Patient’s Choice between a Non-Invasive Prenatal Test and Invasive Prenatal Diagnosis Based on Test Accuracy Yiu Man Chan Tak Yeung Leung Oi Ka Catherine Chan Yvonne Kwun Yue Cheng Daljit Singh Sahota Department of Obstetrics and Gynaecology, The Chinese University of Hong Kong, Shatin, Hong Kong, SAR, China
Key Words Down syndrome · Non-invasive prenatal DNA diagnosis · Amniocentesis · Chorionic villus sampling · Standard gamble
that the test is 95% accurate in the diagnosis of Down syndrome. Current evidence indicates that the detection rate of NIDT will be higher than this level. Health professionals should consider NIDT as an alternative to IPD when counseling women with a positive screening test. © 2013 S. Karger AG, Basel
© 2013 S. Karger AG, Basel 1015–3837/13/0353–0193$38.00/0 E-Mail [email protected] www.karger.com/fdt
Introduction
Women undergoing Down syndrome screening are generally labeled as either ‘low’ or ‘high’ risk of having fetal aneuploidy based on their post-test-adjusted risk [1]. Those indicated as ‘high’ risk are offered an invasive prenatal diagnostic (IPD) procedure, such as amniocentesis or chorionic villus sampling, to confirm the presence of the suspected fetal aneuploidy. Whilst IPD tests are highly accurate and considered the gold standard, they are however not without risk as the procedure itself carries a risk of miscarriage [2]. In addition, IPD tests require interpretation by a skilled laboratory cytogeneticist. The successful isolation of cell-free DNA (cfDNA) in maternal blood and development of non-invasive DNA tests (NIDT) using various sequencing methods have resulted in the introduction of a non-invasive prenatal test (NIPT) for Down syndrome in several countries [3–5]. Current published reports would indicate that cfDNAChan Yiu Man Department of Obstetrics and Gynaecology Prince of Wales Hospital Shatin, Hong Kong, SAR (China) E-Mail chanyiuman @ cuhk.edu.hk
Downloaded by: NYU Medical Center Library 128.122.253.212 - 4/20/2015 3:12:31 AM
Abstract Objective: To assess how pregnant women choose between a non-invasive DNA test (NIDT) and an invasive prenatal test (IPD) based on the accuracy of the test. Materials and Methods: Pregnant women who attended for first-trimester combined screening assessment of risk of Down syndrome were invited to participate in an interviewer-administered survey. Women were asked to choose between NIDT (variable detection rate but no miscarriage risk) and IPD (∼100% detection rate but 0.5–1% miscarriage risk) if their screening test was positive for Down syndrome using the standard gamble technique. Results: 358 women were approached of which 106 (29.6%) were unwilling to participate in the study as it had already been decided in advance which additional test they would have if they were screened positive. Of these 106 women, 70 (19.6%) would only choose IPD whereas 36 (10%) would only choose NIDT. Among those who agreed to undertake the gamble and participate in the study (n = 252), 50% were willing to accept NIDT as an alternative to IPD provided that NIDT had a detection rate of 95%. Conclusion: The majority can accept NIDT as an alternative to IPD provided
Materials and Methods This was a prospective observational study conducted in a university unit in Hong Kong which offered universal first-trimester combined screening [14]. The first-trimester screening test is a free of charge test offered by the Hong Kong Hospital Authority under its universal screening program for Down syndrome since July 2010 [14]. Women who attended the clinic for assessment of fetal Down syndrome risk in April 2012 were invited to participate in an interviewer-administered survey, prior to undertaking their nuchal translucency ultrasound examination. Women who were non-
194
Fetal Diagn Ther 2014;35:193–198 DOI: 10.1159/000356075
Chinese or who did not speak Chinese were excluded from the study. The study was approved by the institutional ethics committee and informed consent was obtained from all study participants. Those consenting to participate were requested to read written information before undergoing a structured interview regarding Down syndrome, NIDT and IPD tests. The written material focused primarily on explaining the incidence, detection and management options relating to Down syndrome, as well as the procedure, detection rate and miscarriage risk of each NIDT and IPD test which would be required should the screening test indicate that their age-adjusted term risk was 1: 250 or higher (screened positive). Prior to conducting the interview, the interviewer specifically reminded all study participants that (1) invasive tests had a 100% detection rate for Down syndrome as well as other fetal aneuploidies but did have a 1% risk of miscarriage [15]; (2) that non-invasive tests did not have a risk of miscarriage, but were not 100% accurate and that the quoted detection rate was 99.1% [16]; (3) that if their NIDT test was positive then a confirmatory invasive diagnostic test would still be required, and (4) that no additional tests would be performed if their NIDT test was negative. All interviews were performed by someone with previous experience on administering the standard gamble technique [17]. The survey was composed of two sections. The first section was designed to elicit relevant demographic information, including maternal age, marital status, educational history, family income level, obstetric history and family history. The second section was designed to elicit patient preferences using the standard gamble metrics. In a standard gamble test [13], participants will be asked to choose from a guaranteed outcome (e.g. being blind for the rest of their life), or who whether they would prefer an alternative state with some chance of a worst outcome (e.g. dying, ‘1-p’) and a complementary chance of an ideal outcome (e.g. continue to live healthily, ‘p’). The risks for the two situations are varied until the participant is indifferent to either of the two options, at which stage the ‘utility’ for the health state under consideration equals ‘p’. This allows quantitative comparison of qualitatively different health states, which guides our understanding of the decision-making process of the patients. In order to ensure that our participants understood the standard gamble metrics, the interviewer first assessed their utilities towards the health state of blindness. The participant was asked to make a decision starting with a probability of 100%, which was then reduced in steps of 5% until it reached 10% after which it was decreased at 1% interval until 2% and thereafter at 0.1% interval, until the participant was unable to make a choice between the two options. After ensuring that participants understood the standard gamble methodology, the exercise was repeated and the preferences towards different prenatal diagnostic tests were then assessed. Women were asked to choose between one of the prenatal tests if their pregnancy was screened positive: (1) the IPD test, which was 100% accurate in the diagnosis of Down syndrome but could result in procedure-related miscarriage (around 1%) or (2) a non-invasive test, which is not associated with procedure-related miscarriage risk but with a variable detection rate for Down syndrome. In order to assess the detection rate of the non-IPD tests that our women can accept as an alternative to IPD test, the assumed detection rate of the test was initially quoted as 75% and varied in steps of 5% until it reached 90%, then increased at 1% interval until 98%, and then at 0.1% interval until it reached 99.9%. The ≈1% procedure-related miscarriage rate quoted in the study is the figure cur-
Chan/Leung/Chan/Cheng/Sahota
Downloaded by: NYU Medical Center Library 128.122.253.212 - 4/20/2015 3:12:31 AM
derived tests for detection of Down syndrome are able to achieve both high sensitivity (≈99%) and specificity (>99%) [5–9]. Universal access to NIDT is at present restricted by its high cost, thus limiting its general availability within the care pathway. There are also significant differences in relative values placed by women and health professionals with regard to NIDT test safety, accuracy and time of results compared to IPD. The recent study by Hill et al. [10] would suggest women highly valued tests with no risk of miscarriage, even though it may be less accurate, compared to health professionals who placed greater emphasis on test accuracy. As NIDT is not yet a diagnostic test due to its limited scope and accuracy, it cannot be regarded as a direct alternative to IPD. It has thus been suggested that NIDT be used as a secondary contingent test in women who have been identified as high risk as a result of a positive screening test, advanced maternal age or past obstetric history. By adopting NIDT as a secondary test it would be expected that it would decrease the number of IPD tests performed which in return would result in fewer miscarriages. Previous studies however would indicate that pregnant women view a Down syndrome-affected birth a worse life event compared to having a procedure-related miscarriage [11, 12]. In contrast, the analysis of Hill et al. [10] indicated that women preferred an NIDT test with no risk of miscarriage and were willing to accept 16% reduction in accuracy in order to avoid having a miscarriage [10]. Although current NIDT detection rates for Down syndrome are lower than invasive tests, the findings of Hill et al. would suggest that pregnant women would accept a less accurate test as an alternative to IPD if their pregnancies were screened to be high risk for Down syndrome. The objective of this study was therefore to assess to what extent pregnant women’s preferences for NIDT or IPD was influenced by the detection rate of the NIDT using the standard gamble metrics, which is the classical method of measuring preferences in economics and health state [13].
Table 1. Demographic characteristics of the study population
Characteristic
Overall (n = 358)
Prefer IPD (n = 70)
Prefer NIDT (n = 36)
Willing to gamble (n = 252)
Age, years Married Education Secondary or below Tertiary or above Family income (HKD per month)
Received: July 12, 2013 Accepted after revision: October 1, 2013 Published online: November 13, 2013
Patient’s Choice between a Non-Invasive Prenatal Test and Invasive Prenatal Diagnosis Based on Test Accuracy Yiu Man Chan Tak Yeung Leung Oi Ka Catherine Chan Yvonne Kwun Yue Cheng Daljit Singh Sahota Department of Obstetrics and Gynaecology, The Chinese University of Hong Kong, Shatin, Hong Kong, SAR, China
Key Words Down syndrome · Non-invasive prenatal DNA diagnosis · Amniocentesis · Chorionic villus sampling · Standard gamble
that the test is 95% accurate in the diagnosis of Down syndrome. Current evidence indicates that the detection rate of NIDT will be higher than this level. Health professionals should consider NIDT as an alternative to IPD when counseling women with a positive screening test. © 2013 S. Karger AG, Basel
© 2013 S. Karger AG, Basel 1015–3837/13/0353–0193$38.00/0 E-Mail [email protected] www.karger.com/fdt
Introduction
Women undergoing Down syndrome screening are generally labeled as either ‘low’ or ‘high’ risk of having fetal aneuploidy based on their post-test-adjusted risk [1]. Those indicated as ‘high’ risk are offered an invasive prenatal diagnostic (IPD) procedure, such as amniocentesis or chorionic villus sampling, to confirm the presence of the suspected fetal aneuploidy. Whilst IPD tests are highly accurate and considered the gold standard, they are however not without risk as the procedure itself carries a risk of miscarriage [2]. In addition, IPD tests require interpretation by a skilled laboratory cytogeneticist. The successful isolation of cell-free DNA (cfDNA) in maternal blood and development of non-invasive DNA tests (NIDT) using various sequencing methods have resulted in the introduction of a non-invasive prenatal test (NIPT) for Down syndrome in several countries [3–5]. Current published reports would indicate that cfDNAChan Yiu Man Department of Obstetrics and Gynaecology Prince of Wales Hospital Shatin, Hong Kong, SAR (China) E-Mail chanyiuman @ cuhk.edu.hk
Downloaded by: NYU Medical Center Library 128.122.253.212 - 4/20/2015 3:12:31 AM
Abstract Objective: To assess how pregnant women choose between a non-invasive DNA test (NIDT) and an invasive prenatal test (IPD) based on the accuracy of the test. Materials and Methods: Pregnant women who attended for first-trimester combined screening assessment of risk of Down syndrome were invited to participate in an interviewer-administered survey. Women were asked to choose between NIDT (variable detection rate but no miscarriage risk) and IPD (∼100% detection rate but 0.5–1% miscarriage risk) if their screening test was positive for Down syndrome using the standard gamble technique. Results: 358 women were approached of which 106 (29.6%) were unwilling to participate in the study as it had already been decided in advance which additional test they would have if they were screened positive. Of these 106 women, 70 (19.6%) would only choose IPD whereas 36 (10%) would only choose NIDT. Among those who agreed to undertake the gamble and participate in the study (n = 252), 50% were willing to accept NIDT as an alternative to IPD provided that NIDT had a detection rate of 95%. Conclusion: The majority can accept NIDT as an alternative to IPD provided
Materials and Methods This was a prospective observational study conducted in a university unit in Hong Kong which offered universal first-trimester combined screening [14]. The first-trimester screening test is a free of charge test offered by the Hong Kong Hospital Authority under its universal screening program for Down syndrome since July 2010 [14]. Women who attended the clinic for assessment of fetal Down syndrome risk in April 2012 were invited to participate in an interviewer-administered survey, prior to undertaking their nuchal translucency ultrasound examination. Women who were non-
194
Fetal Diagn Ther 2014;35:193–198 DOI: 10.1159/000356075
Chinese or who did not speak Chinese were excluded from the study. The study was approved by the institutional ethics committee and informed consent was obtained from all study participants. Those consenting to participate were requested to read written information before undergoing a structured interview regarding Down syndrome, NIDT and IPD tests. The written material focused primarily on explaining the incidence, detection and management options relating to Down syndrome, as well as the procedure, detection rate and miscarriage risk of each NIDT and IPD test which would be required should the screening test indicate that their age-adjusted term risk was 1: 250 or higher (screened positive). Prior to conducting the interview, the interviewer specifically reminded all study participants that (1) invasive tests had a 100% detection rate for Down syndrome as well as other fetal aneuploidies but did have a 1% risk of miscarriage [15]; (2) that non-invasive tests did not have a risk of miscarriage, but were not 100% accurate and that the quoted detection rate was 99.1% [16]; (3) that if their NIDT test was positive then a confirmatory invasive diagnostic test would still be required, and (4) that no additional tests would be performed if their NIDT test was negative. All interviews were performed by someone with previous experience on administering the standard gamble technique [17]. The survey was composed of two sections. The first section was designed to elicit relevant demographic information, including maternal age, marital status, educational history, family income level, obstetric history and family history. The second section was designed to elicit patient preferences using the standard gamble metrics. In a standard gamble test [13], participants will be asked to choose from a guaranteed outcome (e.g. being blind for the rest of their life), or who whether they would prefer an alternative state with some chance of a worst outcome (e.g. dying, ‘1-p’) and a complementary chance of an ideal outcome (e.g. continue to live healthily, ‘p’). The risks for the two situations are varied until the participant is indifferent to either of the two options, at which stage the ‘utility’ for the health state under consideration equals ‘p’. This allows quantitative comparison of qualitatively different health states, which guides our understanding of the decision-making process of the patients. In order to ensure that our participants understood the standard gamble metrics, the interviewer first assessed their utilities towards the health state of blindness. The participant was asked to make a decision starting with a probability of 100%, which was then reduced in steps of 5% until it reached 10% after which it was decreased at 1% interval until 2% and thereafter at 0.1% interval, until the participant was unable to make a choice between the two options. After ensuring that participants understood the standard gamble methodology, the exercise was repeated and the preferences towards different prenatal diagnostic tests were then assessed. Women were asked to choose between one of the prenatal tests if their pregnancy was screened positive: (1) the IPD test, which was 100% accurate in the diagnosis of Down syndrome but could result in procedure-related miscarriage (around 1%) or (2) a non-invasive test, which is not associated with procedure-related miscarriage risk but with a variable detection rate for Down syndrome. In order to assess the detection rate of the non-IPD tests that our women can accept as an alternative to IPD test, the assumed detection rate of the test was initially quoted as 75% and varied in steps of 5% until it reached 90%, then increased at 1% interval until 98%, and then at 0.1% interval until it reached 99.9%. The ≈1% procedure-related miscarriage rate quoted in the study is the figure cur-
Chan/Leung/Chan/Cheng/Sahota
Downloaded by: NYU Medical Center Library 128.122.253.212 - 4/20/2015 3:12:31 AM
derived tests for detection of Down syndrome are able to achieve both high sensitivity (≈99%) and specificity (>99%) [5–9]. Universal access to NIDT is at present restricted by its high cost, thus limiting its general availability within the care pathway. There are also significant differences in relative values placed by women and health professionals with regard to NIDT test safety, accuracy and time of results compared to IPD. The recent study by Hill et al. [10] would suggest women highly valued tests with no risk of miscarriage, even though it may be less accurate, compared to health professionals who placed greater emphasis on test accuracy. As NIDT is not yet a diagnostic test due to its limited scope and accuracy, it cannot be regarded as a direct alternative to IPD. It has thus been suggested that NIDT be used as a secondary contingent test in women who have been identified as high risk as a result of a positive screening test, advanced maternal age or past obstetric history. By adopting NIDT as a secondary test it would be expected that it would decrease the number of IPD tests performed which in return would result in fewer miscarriages. Previous studies however would indicate that pregnant women view a Down syndrome-affected birth a worse life event compared to having a procedure-related miscarriage [11, 12]. In contrast, the analysis of Hill et al. [10] indicated that women preferred an NIDT test with no risk of miscarriage and were willing to accept 16% reduction in accuracy in order to avoid having a miscarriage [10]. Although current NIDT detection rates for Down syndrome are lower than invasive tests, the findings of Hill et al. would suggest that pregnant women would accept a less accurate test as an alternative to IPD if their pregnancies were screened to be high risk for Down syndrome. The objective of this study was therefore to assess to what extent pregnant women’s preferences for NIDT or IPD was influenced by the detection rate of the NIDT using the standard gamble metrics, which is the classical method of measuring preferences in economics and health state [13].
Table 1. Demographic characteristics of the study population
Characteristic
Overall (n = 358)
Prefer IPD (n = 70)
Prefer NIDT (n = 36)
Willing to gamble (n = 252)
Age, years Married Education Secondary or below Tertiary or above Family income (HKD per month)
