Non-invasive prenatal testing (NIPT) for Down's syndrome by analysis of cell-free DNA in maternal plasma is changing the way Down's syndrome screening (DSS) is offered in many countries. NIPT is procedurally safe for both mother and fetus, and can be conducted as early as 10 weeks gestation. It is highly accurate, with detection rates of 99.7% and false-positive rates of 0.04% for Down's syndrome in singleton pregnancies (Gil et al, 2017). Due to the small false positive rate, NIPT is considered an advanced screening test rather than a diagnostic test, and confirmation with invasive testing is recommended to confirm a positive result (Gregg et al, 2013; Royal College of Obstetricians and Gynaecologists, 2014; American College of Obstetricians and Gynecologists, 2015).
The need for accessible, high quality written information to facilitate informed decision-making is particularly acute given the potential for women to view NIPT as a routine test (de Jong et al, 2010; Alexander et al, 2015; Silcock et al, 2015; Hill et al, 2016). The importance of providing high quality written information about screening tests for Down's syndrome has also been emphasised by the NHS fetal anomaly screening programme (Public Health England, 2015). A recent study conducted in the USA evaluated the quality of commercially available patient information pamphlets describing NIPT for aneuploidy (Kloza et al, 2015). It concluded that none of the pamphlets addressed all of the recommendations suggested by professional organisations (Benn et al, 2013; Devers et al, 2013; Gregg et al, 2013; American College of Obstetricians and Gynecologists, 2015) and only scored adequately on a quality appraisal tool. In response, they developed their own patient information pamphlet for their patients, with six women reviewing it in focus groups. As far as the authors are aware, there is no patient information that has been developed and validated specifically for use within a public health care system. This is a concern, given the high expected uptake if the test becomes routinely available (Gil et al, 2015). The aim of this study was to develop a patient information leaflet (PIL) to support the future introduction of NIPT into the fetal anomaly screening programme (Department of Health, 2016). This article will describe the approach used to develop and validate the PIL to ensure delivery of information in a format that meets the needs of most women.
Methods
As part of the RAPID (Reliable Accurate Prenatal non-Invasive Diagnosis) research programme, the authors have evaluated the introduction of NIPT into Down's syndrome screening programme in eight maternity units across England and Scotland (The NIPT Evaluation Study) (Hill et al, 2014; Chitty et al, 2016). Development of written information to support pre-test counselling and ensure that women are adequately informed of the purposes, possible outcomes and limitations of NIPT is a key aim of the RAPID programme.
Ethical approval
Research approval for the NIPT evaluation study, which included the development and validation of the PIL was obtained from the National Research Ethics Committee (Camden and Islington).
Development of patient information
Development of the first draft of the PIL was based on the results of qualitative research with women to explore their views and preferences towards NIPT for Down's syndrome (Lewis et al, 2013) and published guidelines regarding NIPT for aneuploidy (Gregg et al, 2013; American College of Obstetricians and Gynecologists, 2015). The draft included information about Down's syndrome; information about the test (such as what conditions it tests for, test accuracy, how the test is conducted, gestation, and test turnaround time); how NIPT accuracy compares with other Down's syndrome screening tests; and options if the NIPT result is positive. It was then circulated for comment to an expert panel comprising an expert in fetal medicine and NIPT, two genetic counsellors, three midwives, and representatives from Antenatal Results and Choices and Genetic Alliance UK. Revisions were subsequently made and circulated for final review. The reading ease of the PIL was then tested using the Flesch method (Flesch, 1948), which resulted in a readability score of 66, indicating that the PIL was easily understood by those with a reading age of 13-15 year olds. No further changes were made at this stage [Supplementary material—available from the editor on request].
Validation of patient information
To evaluate the PIL, a short feedback questionnaire was developed [Supplementary material—available from the editor on request], which included questions from a questionnaire previously used to assess the quality of patient information about cancer (Jones et al, 1999), schizophrenia (Jones et al, 2001) and to support parents of children without a diagnosis (Lewis et al, 2012). It included questions to assess the usefulness, relevance, technicality and scope of the information, measured on a 4-point Likert scale. Additional questions to assess the clarity of the text used to describe specific aspects of NIPT (such as how NIPT works, testing pathway and test accuracy) were also included and measured using the same Likert scale. At the end of the questionnaire, responders were invited to comment on any aspects of the PIL they liked and/or disliked. To further validate the quality of the PIL, qualitative interviews were conducted with women being offered NIPT for Down's syndrome as part of the NIPT Evaluation Study. Quantitative responses were analysed using descriptive statistics performed with SPSS version 22. Qualitative responses (questionnaire free-text comments and interview transcripts) were analysed using thematic analysis facilitated by NVivo software version 10 (Braun and Clarke, 2006).
Recruitment
Recruitment into the overarching NIPT evaluation study is described in detail in the study protocol (Hill et al, 2014). In brief, women were recruited from eight maternity units across England and Scotland between November 2013 and February 2015. All pregnant women offered Down's syndrome screening were informed about the study and given a research participant information sheet during standard counselling for Down's syndrome screening. Following Down's syndrome screening, those women who had a risk higher than 1:1000 were invited to have NIPT. These women received the PIL on NIPT being evaluated and another different participant information sheet, alongside a more detailed discussion on NIPT with their local screening or research midwife. During the initial period of the study, a consecutive subset of women from four sites were invited to evaluate the NIPT PIL by completing the questionnaire.
Within the NIPT evaluation study, a separate subset of women from all eight sites were invited to take part in a nested questionnaire study looking at their views, experiences and informed choice (Lewis et al, 2016a; 2016b). As part of the informed choice study, a subset of women were invited to take part in an interview to explore their experience of being offered NIPT and to assess informed choice in more depth (Lewis et al, 2016a; 2016b; 2016c). During these interviews women were asked for feedback on the PIL they had received.
Results
Respondents
Questionnaires were completed and returned by 145 of the 152 invited participants (95% response rate). All chose to have NIPT, but one high-risk woman also chose invasive testing at the same time as NIPT.
In addition, 81 interviews were conducted where women were asked to provide feedback on the PIL (75% response rate). All but 3 of the 55 low risk women (5.5%) chose to have NIPT, but 7 of the 26 high risk women (26.9%) also chose invasive testing at the same time as NIPT. There was no overlap between women completing questionnaires and those participating in interviews. Demographic data from the questionnaire and interview respondents are detailed in Table 1.
| Questionnaires n=145 (%) | Interviews n=81 (%) | |
|---|---|---|
| Age (years) | ||
| Mean (range) | 34 (18–44) | 36 (22–45) |
| Gestational age at Down's syndrome screening (DSS) (weeks) | ||
| Mean (range) | 12+5 (11+3–16) | 13+0 (11+2–18) |
| Ethnicity | ||
| Caucasian | 104 (72) | 66 (81) |
| Asian | 28 (19) | 8 (10) |
| Black | 10 (7) | 3 (4) |
| Mixed | 2 (1) | 4 (5) |
| Unknown | 1 (1) | 0 (0) |
| Religion | ||
| Christian | 0 (0) | 24 (30) |
| Muslim | 0 (0) | 11 (14) |
| Jewish | 0 (0) | 3 (4) |
| Hindu | 0 (0) | 1 (1) |
| None | 0 (0) | 36 (44) |
| Unknown | 145 (100) | 6 (7) |
| Education | ||
| Degree | 0 (0) | 54 (67) |
| Vocational | 0 (0) | 11 (14) |
| A-Level/GCE | 0 (0) | 7 (9) |
| GCSE/O-Level | 0 (0) | 4 (5) |
| Unknown | 145 (100) | 5 (6) |
| Risk | ||
| Low DSS risk | 127 (88) | 55 (68) |
| High DSS risk | 18 (12) | 26 (32) |
| Parity | ||
| Nulliparous | 75 (52) | 35 (43) |
| Multiparous | 70 (48) | 46 (57) |
| Family income | ||
| Centre A (Central London) | 50 (34) | 28 (35) |
| Centre B (Essex) | 32 (22) | 14 (17) |
| Centre C (South London) | 53 (37) | 19 (23) |
| Centre D (Wiltshire) | 0 (0) | 7 (9) |
| Centre E (Hampshire) | 10 (7) | 12 (15) |
| Centre F (West London) | 0 (0) | 1 (1) |
Quantitative results
The results indicated that women overwhelmingly liked the PIL: 97% said they found all the information on the PIL useful; 91% found all of it easy to read, 95% found all the information relevant; and 71% found there to be sufficient information. The majority of respondents thought the information was at the right technical level (74%) and did not feel overwhelmed by the PIL (69%), with only 3% of women reporting they found the part of the PIL difficult to understand. Generally, women thought there was a sufficient explanation of Down's syndrome (81%) and that the PIL clearly explained how the test works (94%), its accuracy (95%) and the testing pathway (91%), including what happens following a positive NIPT result (88%). Most women thought the PIL provided sufficient information about finding additional information and support (74%) and that the PIL was balanced and unbiased (77%). Examples of responses can be found in Table 2.
| Definitely yes n (%) | To some degree n (%) | Not entirely n (%) | Definitely no n (%) | No response n (%) | |
|---|---|---|---|---|---|
| Did you find the information useful? | 141 (97) | 4 (3) | 0 (0) | 0 (0) | 0 (0) |
| Was the information easy to read? | 132 (91) | 13 (9) | 0 (0) | 0 (0) | 0 (0) |
| Was the information relevant? | 138 (95) | 6 (4) | 0 (0) | 1 (1) | 0 (0) |
| Did you feel overwhelmed with information? | 13 (9) | 34 (23) | 29 (20) | 69 (48) | 0 (0) |
| Did you find the information too limited? | 2 (1) | 8 (6) | 31 (21) | 103 (71) | 1 (1) |
| Did you find the information too technical? | 4 (3) | 6 (4) | 27 (19) | 107 (74) | 1 (1) |
| Did you find the explanation about Down's syndrome sufficient for this leaflet? | 118 (81) | 18 (12) | 5 (3) | 3 (2) | 1 (1) |
| Was the explanation about how the test works clear? | 136 (94) | 9 (6) | 0 (0) | 0 (0) | 0 (0) |
| Was the explanation about the testing pathway clear? | 132 (91) | 13 (9) | 0 (0) | 0 (0) | 0 (0) |
| Was the explanation about the accuracy of NIPT clear? | 137 (94) | 8 (6) | 0 (0) | 0 (0) | 0 (0) |
| Was the explanation about what happens following a positive NIPT clear? | 127 (88) | 8 (6) | 2 (1) | 0 (0) | 8 (6) |
| Does the leaflet provide sufficient information about finding additional info/support? | 116 (80) | 18 (12) | 2 (1) | 0 (0) | 9 (6) |
| Was there anything in the leaflet you found hard to understand? | 4 (3) | 7 (5) | 17 (12) | 107 (74) | 10 (7) |
| Is the leaflet balanced and unbiased? | 114 (79) | 8 (6) | 4 (3) | 6 (9) | 13 (9) |
Qualitative data
Qualitative data from the questionnaires and interviews supported the positive findings from the quantitative responses. Three main themes emerged from the qualitative data analysis which related to content, clarity and lay-out of the PIL.
Content
Women valued having contact details of support groups in case there were any questions at a later stage.
‘It was useful to have some contact details on there as well. I mean, I didn't feel the need to contact anyone about it, but it was useful to know I could have phoned up someone if I'd had any other concerns.’ (Interview P61, high DSS risk, negative NIPT result)
Women also valued the opportunity to have written information to take away with them to read at a later stage and share with their family.
‘It was great and I think it's really important to have it written down because when you're at appointments, you don't always remember everything and you're a bit emotional anyway and it's quite nice to be able to take it away and to take it away and share it.’ (Interview P19, low DSS risk, negative NIPT result)
There were a few suggestions as to areas which could have been covered more in depth in the PIL. One woman wanted more information about how the test worked.
‘How do they work out it's the baby's DNA and not the mum's DNA? How do they know that they're looking at the right thing?’ (Interview P41, high DSS risk, positive NIPT result)
Another woman thought it would be helpful to include additional information on the reasons for inconclusive results and false positives and negatives.
‘The only thing that I find that was missing was (but maybe that's only because I'm a bit of a control freak sometimes) was the reasons why some tests were inconclusive and some tests were false positive and some tests were false negative, so the test results. That's the only thing that was not there and that I was wondering so I looked it up on the internet.’ (Interview P22, High DSS risk, negative NIPT result)
Information on the options and timings related to termination of pregnancy was also suggested by one woman who had received a positive NIPT result.
‘I've retrospectively gone back to that fact sheet and it doesn't say anything about timings and there's nothing up front to say that if you participate in this test these are therefore your timings which therefore means if you want to or need to terminate, these are your options, it doesn't give you that.’ (Interview P8, high DSS risk, positive NIPT result)
Clarity
In general, most women felt that the PIL was clear and easy to understand.
‘It just made everything clear so I had no questions about anything on there because I understood it all and it was really clear.’ (Interview P46, low DSS risk, negative NIPT result)
For the majority of participants, comments indicated that the language was pitched at the right level, as highlighted by comments including ‘very easy to understand with no technical terms’ and ‘straightforward language’. However, a small number of concerns were raised relating to the language being overly technical, which may be off-putting or difficult to understand by people whose first language was not English or who have learning difficulties.
‘I just don't think it needs to be that medical or scientific, if you see what I mean—give them like, the basic on what it is and they would be quite … I think people would be more comfortable with that.’ (Interview P13, low DSS risk, negative NIPT result)
‘For me it was fine, but for those who don't speak English or have learning difficulties, it could be illustrated in a more simpler way. Yeah, that's my only concern about people who are unable to take in all that kind of information.’ (Interview P30, low DSS risk, negative NIPT result)
One woman suggested that visual representations of the information might be more suitable for some readers.
‘Perhaps an infographic would be easier for less educated or people whose first language is not English.’ (Questionnaire A5, low DSS risk, negative NIPT result)
Layout
Regarding the layout of the PIL, the use of subheadings was found to be useful, as highlighted by one woman who said she ‘particularly like[d] it where it is question and answer style’ (Questionnaire C49, low DSS risk, negative NIPT result). Another commented that the ‘subtitles make it very easy to locate information that you want to refer to’ (Questionnaire E7, low DSS risk, negative NIPT result).
A number of women gave feedback related to the PIL's layout being ‘very word heavy’ and ‘compact’ and suggested that PIL could be enhanced using pictures, colour and spacing the text out.
‘It was just a lot on the page, so if it could be broken down, maybe just visually a bit, sort of, easier to read, I think that might help people.’ (Interview P14, low DSS risk, declined NIPT)
Key areas of information
During the development and evaluation of the PIL, seven key areas of information women need when considering NIPT were identified (Figure 1). These areas can be explored more deeply during pre-test counselling to facilitate shared decision making, and should be incorporated into the development of any additional sources of information for expectant parents or health professionals, such as websites and guidelines.
Final leaflet
Following analysis of the quantitative and qualitative data further amendments were made. Additional information was added regarding how the results would be delivered; although it was decided that in-depth information about the technical aspects behind NIPT was not required as this might make the PIL overly complex and was unlikely to be of interest to most readers. Further information on the options and timings related to termination of pregnancy was also deemed unnecessary as it would be more appropriate to provide this as part of the pre-test counselling for patients requesting more detail, and may vary depending on local practice. Additionally, a more in-depth PIL could be developed and validated to provide more technical information about how NIPT works, including the possible reasons for false positives, such as confined placental mosaicism or maternal malignancy. Following comments that the PIL was word heavy, the PIL was adjusted so that the text was spaced out and further enhanced by pictures and colour.
Discussion
Ensuring that patients have access to good quality written information about NIPT that is both accurate and balanced is important, particularly given that studies have found that the media (Lewis et al, 2015), and NIPT provider websites (Skirton et al, 2015), are more likely to include portray NIPT as positive, with more emphasis given to the benefits than the potential limitations of the test. The method used to develop this PIL has a number of strengths. It was developed using both quantitative and qualitative data from women being offered NIPT in a clinical setting, ensuring that the PIL was evidence-based and focused on their particular information needs. Moreover, the mixed methods approach using qualitative and quantitative methodologies to evaluate the PIL also allowed for findings to be validated through triangulation.
The majority of feedback received about the PIL, from both the quantitative and qualitative arms of the study, was positive, suggesting that the PIL was well received by women and addressed their information needs adequately. There were a small number of concerns, namely that the language was too technical, but in contrast, some women suggested that the information was too limited. This highlights the complexity of trying to develop a ‘one size fits all’ approach to written patient information and highlights the need to provide pre-test counselling as well. Pre-test counselling, ideally face-to-face, allows the health professional to gauge and ensure patient understanding, and tailor information to the individual's needs to facilitate individualised, informed decision-making. In order for health professionals to provide effective pre-test counselling, specialist training in prenatal counselling about NIPT is essential so that they feel competent to impart information to patients and support a shared decision-making process. This has been addressed as part of the RAPID programme through the development of a training workshop, along with supplementary information leaflets and website for health professionals (Oxenford et al, 2017). Given the concerns that have been expressed regarding the facilitation of individualised and informed decision-making in the context of Down's syndrome screening (van den Berg et al, 2005; Potter et al, 2008), these steps are imperative to ensuring that introduction of NIPT into the Down's syndrome screening pathway does not encounter similar issues. The PIL could also be used as a starting point for the development of an intervention to further enhance the decision-making process for NIPT, such as a decision aid, a tool designed to assist individuals to make informed decisions about their health care. A systematic review of decision aids used in a variety of health care settings, including prenatal screening, has shown that they can improve patient knowledge and facilitate decision-making that are consistent with their values (Stacey et al, 2014). While much is known about the multiple factors that influence women's decisions to accept or decline Down's syndrome screening tests (Reid et al, 2009; Crombag et al, 2013), future research would be needed determine whether the introduction of NIPT would bring different factors that would need to be considered in the development of any interventions to support decision-making.
While the PIL in this study was well accepted by women, it is important to consider that people now get their information from a variety of different sources, such as newspapers, magazines, websites, chat forums, social media and via different mediums, including online, video and phone applications. Accordingly, the final PIL developed in this study was made freely available on the internet but it will be imperative for services to develop information about NIPT in other formats to cater for their particular patient demographic. For example, this PIL may be unsuitable for women whose first language is not English, or women with low literacy levels. In order to reach all audiences, translation to multiple languages and production in other formats, such as easy read and braille, will be required. Regular review of the information and tailoring to the platform being used will be essential, given that NIPT is a rapidly changing technology and different providers deliver NIPT with different performance.
Study limitations
As evaluation of the information described here was part of a research study, respondents received a number of written documents alongside the PIL, including two research participant information sheets and a consent form. As such, it cannot be known whether they only considered the PIL when responding to the questionnaire. Nevertheless, attempts were made to minimise this potential bias by ensuring that the research team asked participants to read the PIL during pre-test counselling and to answer questions relating to that PIL specifically. Another limitation is that only women who accepted NIPT completed the questionnaire and as such, it is not known whether women who declined NIPT were as positive. The study was further limited by only offering the questionnaire to women and not their partners, who will often be involved in pregnancy-related decisions, such as Down's syndrome screening (Jaques et al, 2004; St-Jacques et al, 2008). Further evaluation with partners would provide additional insight into their information needs, which may be different from those of pregnant women. The questionnaire and interview respondents were primarily Caucasian, well-educated and older and therefore we do not know whether these findings are generalisable. It will therefore be important to extend the validation to women from other sociodemographic groups, including those from minority ethnic groups and low educational backgrounds. This is particularly important given that these groups are less likely to make informed decisions and this is more likely to be related to a lack of understanding of the test (Lewis et al, 2016a).
Conclusion
In this study, an evidence-based PIL for women considering NIPT for Down's syndrome was developed and validated using a mixed methods approach. The PIL was well received and, following some minor amendments, is now freely available for health professionals to give to women considering NIPT provided by the North East Thames Regional Genetics Service at Great Ormond Street Hospital for Children NHS Foundation Trust. As information may vary between NIPT providers, a generic version of the PIL is available upon request from the RAPID team, which can be easily modified with test-specific information. The generic version includes the seven key areas of information that women need when considering NIPT, which were identified during the development of this PIL. These key areas of information could also be used to direct the development of other information sources, including guidelines for health professionals providing pre-test counselling to expectant parents. The development and validation of an intervention such as a decision aid may also provide a structured approach to shared decision making between healthcare professionals and expectant parents.
Practice implications
The development and validation of a PIL about NIPT for Down's syndrome has provided insight into the information needs of women. The validated PIL could inform the development of resources for women during the future introduction of NIPT into the UK fetal anomaly screening programme. The seven key areas of information can be explored more deeply during pre-test counselling to facilitate shared decision-making.