Preferences for interventions designed to increase cervical screening uptake in non‐attending young women: How findings from a discrete choice experiment compare with observed behaviours in a trial

Abstract Background Young women’s attendance at cervical screening in the UK is continuing to fall, and the incidence of invasive cervical cancer is rising. Objectives We assessed the preferences of non‐attending young women for alternative ways of delivering cervical screening. Design Postal discrete choice experiment (DCE) conducted during the STRATEGIC study of interventions for increasing cervical screening uptake. Attributes included action required to arrange a test, location of the test, availability of a nurse navigator and cost to the National Health Service. Setting and participants Non‐attending young women in two UK regions. Main outcome measures Responses were analysed using a mixed multinomial logit model. A predictive analysis identified the most preferable strategy compared to current screening. Preferences from the DCE were compared with observed behaviours during the STRATEGIC trial. Results The DCE response rate was 5.5% (222/4000), and 94% of respondents agreed screening is important. Preference heterogeneity existed around attributes with strong evidence for test location. Relative to current screening, unsolicited self‐sampling kits for home use appeared most preferable. The STRATEGIC trial showed this same intervention to be most effective although many women who received it and were screened, attended for conventional cytology instead. Conclusions The DCE and trial identified the unsolicited self‐sampling kit as the most preferred/effective intervention. The DCE suggested that the decision of some women receiving the kit in the trial to attend for conventional cytology may be due to anxieties around home testing coupled with a knowledge that ignoring the kit could potentially have life‐changing consequences.


| INTRODUC TI ON
For a growing proportion of young women, embarrassment, anxiety, fear and inconvenience around testing are barriers to cervical screening. [1][2][3][4] The reluctance of many to engage with the National Health Service (NHS) Cervical Screening Programme (CSP) is reflected in national screening statistics. Five-year screening coverage rates in England are lowest amongst 25-to 29-year-old women and are falling (72% in 2005 to 65% in 2017), whilst the incidence of invasive cervical cancer has begun to increase. 5,6 Similarly in Scotland, non-attendance is highest amongst young women, with a screening uptake rate during 2017/2018 of just 62% in those aged 25 to 29 years. 7 Furthermore, screening uptake is known to be lower with increasing levels of deprivation, with uptake rates amongst young women shown to vary as much as 4% between highest and lowest deprivation categories. 8,9 This is a concern and is driving research into tailored interventions aiming to address women's barriers to screening and which could potentially be embedded within the existing CSP to increase uptake.
The decision to invest in any such interventions should be informed by evidence on effectiveness and cost-effectiveness.
Complementary data on the acceptability of an intervention to women might also reassure policymakers that the intervention will work in routine practice. Discrete choice experiments (DCEs) offer a way of eliciting preferences for the characteristics or attributes of an intervention; they also provide information on the trade-offs (the decision to sacrifice the benefits of one attribute in favour of another) that respondents are prepared to make between attributes.
DCEs have been used in health-care settings to improve the design and delivery of patient services. [10][11][12] Their use also extends to cancer screening programmes; a systematic review identified 22 stated preference studies published between 1990 and 2013 addressing breast, cervical and colorectal cancer screening. 13 The DCE reported in this paper was conducted as part of the STRATEGIC study (Strategies to Increase Cervical Screening Uptake at First Invitation) which evaluated novel interventions intended to make screening more acceptable to young women receiving their first invitation. 14,15 Interventions were evaluated in a phased cluster randomized trial conducted in the Greater Manchester area of England and the Grampian area of Scotland. In phase 1, pre-invitation information leaflets and Internet booking options were trialled to increase initial attendance. In phase 2, young women who had not attended within six months of an initial invitation were randomized to one of six alternatives: a human papillomavirus (HPV) self-sampling kit (SSK) for home use which was trialled as an unsolicited (sent) and a solicited (offered) intervention, a pre-specified timed appointment (PTA) for a routine screening test, access to a nurse navigator (NN) whom women could contact to discuss concerns about screening and for help in navigating the screening process, a choice between a PTA and the NN, or no further action. The feasibility of these interventions was confirmed in a pilot study. The primary outcome measure for phase 2 of the trial was uptake in screening at 12 months post-initial invitation. Cost-effectiveness was also assessed. 15,16 The DCE was conducted simultaneously with the trial. Its objectives were to determine young women's preferences for the individual characteristics of the phase 2 interventions and to predict which interventions were likely to be most preferable to women.
The study design also afforded a unique opportunity to compare the effectiveness of the STRATEGIC interventions with their potential acceptability to women if implemented widely in the UK. Given the defining characteristics of the study cohort (a hard to reach, growing group of young women about whom little is known regarding their preferences for screening interventions), this is a novel study which should be of interest to policymakers, clinicians, researchers and women themselves.

| Designing the discrete choice experiment
In a DCE, participants are presented with a number of questions, each asking them to make a choice between two or more alternatives (together referred to as a choice set). The alternatives within a choice set are described using a set of common attributes (eg in a study of follow-up care, attributes might include frequency of follow-up, clinical personnel seen and duration of appointment). 10 Each attribute has values (levels), and the levels taken by at least one attribute are systematically varied between the alternatives (eg followup frequency might be annual in one alternative and 2 yearly in the other). Respondents then select their preferred alternative. 17 Here, the alternatives considered were different means of delivering the CSP (see Table 1). The DCE was developed taking the following steps.

| Identifying attributes and levels
The published evidence around barriers to cervical screening helped develop a topic guide for planned qualitative interviews with 20-30 women. 3,4 Interview invitations were sent to a sample of women women receiving the kit in the trial to attend for conventional cytology may be due to anxieties around home testing coupled with a knowledge that ignoring the kit could potentially have life-changing consequences.

K E Y W O R D S
cervical cancer, discrete choice experiments, heterogeneity, preferences, screening uptake, United Kingdom, young women invited to take part in phase 1 of STRATEGIC and to women in the phase 2 pilot study. It was the intention to use purposive sampling so as to conduct interviews in a mix of women offered the phase 2 interventions (HPV SSK, PTA, NN), and furthermore in those who had accepted and declined the intervention. A first batch of 600 invitations yielded four respondents; a second batch of 500 yielded one additional respondent. These five women underwent semistructured telephone interviews. All had been allocated the sent HPV SSK but prior to interview it was not known if they had used the kit. Interviews were digitally recorded, transcribed verbatim and analysed using deductive content analysis. 18 For the women interviewed, four issues emerged as being important. Flexibility, particularly around the booking process and attending for the screen (fitting this into busy daily life), was a key factor. Expertise was also important, with regard to self-testing versus testing by a health professional. The emotional impact of screening was evident, centring upon the discomfort of testing (regardless of location), and the embarrassment of having a test administered by a health professional. Finally, women raised ideas around greater normalization of screening, including the provision of more information of the process, as well as increased use of reminders (delivered, eg by text message).
As only five women were interviewed, findings were reviewed against published evidence on the barriers to cervical screening and found to be broadly consistent. Together, STRATEGIC's clinical, quantitative and qualitative teams ensured the finalized list of attributes captured aspects of screening that were important to women and also described features of the phase 2 interventions. Table 1 shows these attributes, their levels, and how each relates to the interventions being studied. Inconvenience around the booking process was a concern, as was a dislike of the test per se, which potentially makes calling for an appointment difficult. As the phase 2 interventions offered different approaches for arranging a screen (eg with a PTA the appointment is made for the woman), we included the attribute 'Action required by you personally to arrange a test?' with associated levels 'Yes' and 'No'. The inconvenience of attending, coupled with the embarrassment of a gynaecological examination, could potentially be overcome by the use of a HPV SSK. Some women, however, have concerns around their competence to perform a home test. 19 To account for these aspects, we included the attribute 'Location of the test' with levels 'GP surgery/clinic' and 'Home'.
Women's perceived need for more information plus their fears around the examination could be allayed by a trained nurse prior to screening. As the NN could potentially be an adjunctive option with any of the interventions, it was included as an attribute in its own right. Finally, a cost attribute was included with four values reflecting the approximate costs to the NHS of each of the interventions.

| Experimental design
The attributes and levels in Table 1  attributes within a choice set never take the same level value (thereby forcing respondents to trade on all attributes and eliciting maximum information). [22][23][24] The design approach suggested little informational benefit would be gained by using more than 16 choice sets, but given the challenges engaging these women with the qualitative interviews, we opted for 12 sets to reduce respondent burden (see Supplemental File 1).

| Piloting of the questionnaire
As well as the choice sets, women completing the questionnaire reported their general views on the current screening programme and provided demographic information. In addition to the paper-based questionnaire, an online version was developed using LimeSurvey (www.limes urvey.org). The weblink was sent out with the paperbased questionnaire, thus providing women with a choice as to how to respond. To encourage participation, women were offered a £10 high-street voucher.
Piloting of the questionnaire took place between July and September 2014 in young women not responding to their initial screening invitation. The English and Scottish screening agencies identified eligible women and mailed out the questionnaires.
One thousand questionnaires were sent to women in Greater Manchester (n = 650) and Grampian (n = 350), and 54 (5.4%) were returned (11/54 (20%) using the online version). Responding women appeared to complete the questionnaire without difficulty, and in response to a small number reporting, it was unclear when the NN would be available, the words 'prior to the appointment' (Table 1) were added. A graphic design team improved the look of the questionnaire, the final version of which and the accompanying information leaflet are shown in the Supplemental File 1.

| Administering the final questionnaire
The main DCE data collection was carried out between mid-July 2015 and mid-September 2015. Three thousand questionnaires were sent to women in Greater Manchester (n = 2000) and Grampian (n = 1000

| Statistical analysis
Descriptive statistics were used to summarize participant demographics and women's views of screening. For the 12 choice sets, we assumed each choice was made in accordance with random utility theory which states that when faced with two or more alternatives, each of which generate a level of utility (satisfaction), an individual will select the alternative maximizing their utility. 17  is a constant term and if statistically significant suggests respondents have a general propensity to select alternative one over alternative two in choice sets, all else being equal. Its inclusion in the model allows this bias to be controlled for. 17 As action, location and nurse are categorical variables, the sign of the estimated coefficients 1 , 2 and 3 denotes whether a move from the reference category for each variable (from no to yes for action, home to GP clinic for location and no to yes for nurse) results in an increase or decrease in overall utility. For cost, the directional change in utility resulting from an increase of £1 is given by 4 . Analyses were performed in Stata MP using the 'mixlogit' command. 26,27

| The STRATEGIC trial results
In phase 2 of the STRATEGIC trial at 12 months post-initial invitation, screening uptake in the no action (control) arm was 16.2%. 14,15 Only two of the interventions -the sent HPV SSK and the PTAresulted in significantly higher 12-month screening uptake rates of 21.3% and 19.8%, respectively (associated odds ratios 1.51 [95% CI 1.20-1.91] and 1.41 [95% CI 1.14-1.74]). 14,15 The NN resulted in a significant reduction in screening uptake. Of the women who received a sent HPV SSK and were screened, more than two thirds underwent only a conventional cytology test. 14,15 The accompanying cost-effectiveness analysis concluded that the sent HPV SSK and PTAs were likely to be cost-effective. 16

| RE SULTS
Of the 3000 questionnaires sent, 168 (5.6%) were completed (98  Table 2 shows respondents' characteristics. Almost three fifths were from England and the overall mean age was 24.6 years. Women from Scotland were younger (reflecting the lower age threshold for commencement of screening in Scotland at the time). The majority of women were of White ethnicity and just under a half had been educated to university level. Almost three fifths were in employment.

| Descriptive data analysis
When presented with the statement 'screening for cervical cancer is important', almost two thirds of women (64%) indicated that they strongly agreed and a further 30% selected the 'agree' option. Table 3 shows the mean coefficients for each attribute from the model. Each of the attributes had a significant impact upon women's utility. The alternative specific constant was also significant (with a negative sign), suggesting that all else being equal, women selected the first of the two options presented. When considered in isolation, having to take action to arrange a test, having a test at the GP surgery/clinic and higher screening costs resulted in a decline in utility. The NN was associated with an increase in utility. Aside from the constant, the standard deviations for all coefficients were significant, suggesting considerable heterogeneity between women in their preferences. The standard deviation for the location coefficient was particularly large. Table 4 reports the predictive analysis. Women appeared indifferent between the current CSP and the use of PTAs; predicted probabilities of selecting each option were 0.503 and 0.497, respectively. Model predictions suggested both offered and sent SSKs were preferred to current screening practice. In contrast, current screening practice appeared preferable when compared with a programme in which a NN was offered as a standalone intervention.

| Comparing DCE and trial results
In the DCE predictive analysis, the sent HPV SSK was the most preferred alternative, which was also identified in the STRATEGIC trial as one of the two interventions potentially effective. The other intervention was the PTA, yet women in the DCE appeared indifferent between a PTA and the current CSP. The offered HPV SSK was preferred by women in the DCE but was not effective in the trial, and in both studies, the NN did not appear to be considered beneficial by women.

| D ISCUSS I ON
This DCE is the first to assess preferences for alternative means of delivering cervical screening in a group of young women reluctant to engage with the current NHS CSP. Additionally, the STRATEGIC study design afforded a unique opportunity to consider women's stated preferences alongside observed behaviours in the trial, and so provides additional information to help interpret the trial findings.
The study was conducted in accordance with good practice guidance for DCEs. [28][29][30] Qualitative interviews, the published literature and expert opinion were used to identify attributes. Additionally, a cost attribute was included to allow estimation of the marginal monetary benefit women placed upon each of the remaining attributes.
For example, the monetary value of the benefit achieved when moving from a GP clinic setting to a home testing setting. However, as we were interested in women's preferences for screening programmes as defined by combinations of attributes, we questioned the meaningfulness of these individual values and ultimately chose not to report them. Careful consideration was given to the experimental design in a bid to increase participation, the questionnaire was piloted, and the results used to inform sample size calculations for the main survey. Choice data were analysed using a discrete choice model accounting for different sources of random heterogeneity.
Almost 94% of women surveyed either strongly agreed or agreed with the statement 'screening for cervical cancer is important'. This is a notable finding, which has been observed elsewhere. In conducting interviews with young non-attending women for example, Waller et al found many were positively disposed towards cervical screening despite making a decision not to attend. 2 The mean coefficients from the model ( heterogeneity between women in terms of their preferences for the location of the test. This is perhaps not surprising as this attribute will capture dual (and opposing) concerns relating to embarrassment (whereby home testing is preferred) and expertise required to perform the test (whereby GP clinic-based testing is preferred).
The ability to consider the DCE findings alongside the STRATEGIC trial results is a novel aspect of this work. In the DCE predictive analysis, women stated an obvious preference for an alternative exemplifying the use of a sent HPV SSK. The trial similarly showed sent HPV SSKs to be the most effective and cost-effective intervention; however, it also unexpectedly revealed that many women screened after receiving a sent HPV SSK did not use the kit, but attended for conventional cytology screening.
A possible explanation is that there exists a sub-group of women for whom home testing is not preferable. The DCE showed location was most important to women and revealed significant heterogeneity in preferences for this attribute. For some women, home may not be a safe or a private environment. Furthermore, research into women's perspectives of HPV self-testing has identified concerns including low confidence in the ability to self-sample, worries that samples may be lost or contaminated in the post, that HPV tests may be inferior to cytology tests, and fears about a lack of professional input and low confidence in the test result. 19 Here, it is possible that uncertainties around the HPV SSK per se exerted a greater influence on women's screening decisions than the general process of how self-sampling is delivered as covered by the DCE. Given concerns around HPV SSKs, but with an acceptance of the importance of screening, many women appeared to have been 'nudged' into attending for conventional cytology after receiving a kit at home. 14 The trial also identified PTAs as a potentially effective option for increasing screening uptake, whereas women in the DCE appeared indifferent between routine screening appointments they make themselves and PTAs (Table 4). It is possible that differences exist between women's preferences for hypothetical scenarios (in the DCE, women may have been communicating their general dislike of clinic-based testing per se, regardless of how the appointment was arranged) and the decisions they face in reality; women may still dislike clinic-based tests but are more likely to respond to a PTA because it removes the onus on them to arrange an appointment, and, as discussed above, they recognize that a decision not to attend could potentially have life-changing consequences.
In the DCE, the offered HPV SSK was preferred to the current CSP, but was not effective in the trial. Again it is possible that whilst women in principle prefer the idea of home testing, in reality, with only an offer of a HPV SSK, the onus is still on them to request a kit.
For many, this may still be a difficult first step to take. This study is not without limitations. In developing the attributes and levels, only five women were interviewed; however, drawing on the literature and expert views ensured confidence in the final set used for the DCE. The response rate of just 5.5% to the DCE is also a concern. Despite efforts to increase participation, the defining characteristic of this cohort of women, that is that they are non-engaged, meant that engaging them with a DCE about a screening programme in which they have chosen not to participate was challenging. Other DCEs in the area of cervical screening have similarly reported low response rates in sub-groups of women eligible for but not attending screening. 32 As non-responding women are likely to be the most at-risk group, future studies may need to explore alternative ways of engaging such women to understand the issues they face with regard to cervical screening.
Given the low response rate, there is potential for non-response error. However, it is difficult to know how we might have mitigated this further. Watson et al used meta-regression to identify factors of DCEs influencing response rates, and reported more than 2-4 attributes were associated with reduced response rates but failed to find a negative association between response rates and the number of attribute levels. 33 The use of reminders increased response rates, but the way this survey had to be ad- will be extended to boys of the same age. 34 Studies have reported significant reductions in low-and high-grade cervical intraepithelial neoplasia amongst those vaccinated, yet maintain that HPV vaccination in combination with regular cervical screening is the best way to prevent against cervical cancer, as vaccination does not protect against all types of cancer-causing HPV. 35 Research into the effectiveness and acceptability of interventions, which increase the likelihood of a young women attending for cervical screening, therefore, continues to be paramount.

| CON CLUS IONS
This paper presents previously unreported data on the stated preferences of a group of hard to reach young women for the characteristics of interventions, which could potentially be embedded within the NHS CSP to increase screening uptake. In the DCE as well as the STRATEGIC trial, the sent SSK was the most preferred/effective alternative. Women in the DCE strongly acknowledged the importance of screening yet differed significantly in their preferences for the location of the test. This could offer a potential means of understanding why many women screened after receiving the sent HPV SSK in the trial attended for conventional cytology.
Policies bringing unsolicited screening interventions directly to women appear likely to be most effective. Additionally, such interventions might also cause women to contemplate the potential implications of not responding to the intervention (a PTA or HPV SSK) in front of them; however, this would need to be explored more fully by future research. The low DCE response rate and the potential implications for the generalizability of the results must be acknowledged. Future research in this area should consider whether such questionnaires, which may be intimidating for respondents, offer the best means of engaging with a hard to reach cohort of women.

STRATEGIC was granted ethical approval by NRES Committee North
West -Greater Manchester North on 01/11/11 (REC reference 11/ NW/0624). The DCE was included in the original protocol and in the ethical amendment number 5 (dated 11/09/12) with a further amendment (number 8) approved on 29/01/14. The study was conducted in accordance with the ethical principles outlined in the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. Informed consent was obtained from all individual participants included in the study.

ACK N OWLED G EM ENTS
We are grateful to Sara Rodgers and Laura Clark at the University of York for conducting the qualitative interviews. We are grateful to Maggie Redshaw at the National Perinatal Epidemiology Unit (NPEU) for helpful suggestions on how to improve the response rate in our study. We also would like to thank the NPEU design team who significantly improved the look of our final questionnaire, and the NPEU administration team for their assistance preparing the mail-out material. Special thanks are given to our data entry team Sissi Hernandez-Quesada, Jacob Stevens and Pamela White. We would also like to express our gratitude to the teams at the English and Scottish screening agencies for their willingness to collaborate in this study. Finally, we would like to thank all of the women who completed the DCE questionnaire and took part in the STRATEGIC trial; without them, this work would not have been possible.

CO N FLI C T O F I NTE R E S T
None.

DATA AVA I L A B I L I T Y S TAT E M E N T
Data available on request from the authors.