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Preferences for genetic testing for colorectal cancer within a population based screening program: a discrete choice experiment Jorien Veldwijk1,2, Mattijs S Lambooij1, Frank G J Kallenberg3, Henk J van Kranen1,4, Annelien L Bredenoord2, Evelien Dekker3, Henri A Smit2 and G Ardine de Wit1,2Received 11 February 2015; Revised 28 April 2015; Accepted 29 April 2015Advance online publication 3 June 2015 Top of pageAbstractThis study explored individuals preferences for genetic testing for colorectal cancer (CRC) in a screening situation and their willingness to participate in genetic testing for Lynch syndrome, familial adenomatous polyposis (FAP), and familial where can i buy a pandora bracelet online colorectal cancer (FCC).

For that purpose, 532 respondents aged 55 years completed a Discrete Choice Experiment. Using panel latent class models, the preferences for two screening situation characteristics (the probability of being genetically predisposed and the probability of developing CRC) and screening test characteristics (the frequency of preventive colonoscopies and CRC survival) were estimated. Based on these preferences, respondents willingness to participate in the three screening initiatives was estimated. Lower educated respondents and respondents who express serious anxiety and worries found colonoscopy frequency and the probability of developing CRC relatively more important and survival relatively less important compared with higher educated respondents and respondents who express no anxiety and worries. These differences in preferences resulted in opposite preferences for participation in FCC and FAP screening. In conclusion, the general population is willing to participate in genetic screening for CRC. If individuals are suspected of genetic or familial CRC, they should at least be informed about their increased risk of being genetically predisposed and about the importance of participating in all preventive follow up colonoscopies in order to maximize survival. Top of pageIntroductionAlthough genetic screening, in addition to population based colorectal cancer (CRC) screening, may be beneficial for those who run a higher risk of developing CRC, there sale of pandora charms is a discussion about whether this additional form of screening is advisable and desirable.1, 2, 3, 4 CRC is one of the most commonly diagnosed cancers and the leading cause of death among all cancer types worldwide.5 Prognosis, treatment intensity and the 5 year survival rate significantly improve if CRC is diagnosed at an early stage.6, 7 Moreover, CRC can actually be prevented, because it is usually preceded by a slow progressive premalignant lesion (an adenomatous polyp), which may become cancer but can be detected and removed during colonoscopy.7 Therefore, population based screening programs for CRC are recommended and widely implemented in Western countries. Within these programs, there is little attention for genetically predisposed individuals who run a higher risk of developing CRC. About 5 of all diagnosed CRCs is of genetic origin.8, 9, 10 This relatively small percentage actually reflects a substantial number of CRC patients given the high incidence of CRC in the general population. Offering genetic testing to participants in a population based CRC screening program after a positive colonoscopy and with a familial cancer history (ie, screening situation) will identify genetically predisposed individuals and their families.11, 12 By including genetic screening in current population based CRC screening programs, CRC related morbidity and mortality may further decrease due to increased surveillance of cases and their relatives.11, 12, 13 However, genetic testing raises several ethical and counseling challenges.14, 15 For instance, knowing that one is at risk to develop cancer might induce fear of actually developing cancer, possibly with a negative impact on a person quality of life.16, 17 Positive test results may also have a severe impact on the family of the tested individual,16, 17, 18 as they themselves might run a higher risk www pandora com pandora bracelets of developing cancer as well. Moreover, the general population often holds unrealistic expectations about the accuracy with which genetic screening tests can predict future disease status.17, 19 Despite these potential negative consequences, the general population shows great interest in genetic screening and has a positive attitude towards such screening initiatives.16, 20, 21, 22 Previous research shows that individuals are willing to take part in genetic screening when the test aims to identify an increased risk for a monogenic form of a common disease, when adequate treatment and prevention options are available and when clinicians recommend screening.21, 23, 24, 25 To date, no research has been conducted into studying the preferences of the general population for genetic testing for CRC specifically within a screening situation. Therefore, this study aims to explore individual preferences concerning genetic testing for CRC within a population based CRC screening program. A further aim is to estimate whether individuals are willing to participate in genetic testing for (1) Lynch syndrome, (2) familial adenomatous polyposis (FAP) and (3) familial colorectal cancer (FCC) within a screening situation. Top of pageMaterials and methods Discrete choice experiment (DCE)DCEs are increasingly being used to determine an individual preferences regarding different characteristics of interventions or medical treatments.26 This method is based on the Random Utility Theory. This theory assumes that any intervention or treatment can be described by its characteristics or such as the probability of a positive test outcome. The preferences of an individual for an intervention or treatment is determined on the basis of the of the attributes, such as 1, 3 or 15 probability that the test outcome is positive.26 Hypothetical situations are constructed by varying the levels of the attributes. Respondents are provided with a series of tasks that consist of at least two situations. They are asked to choose the situation they prefer most within every choice task. DCE developmentTo construct the DCE used for this study, possible attributes were identified from previously published studies,21, 22, 23, 24, 27 six expert interviews (ie, a scientist with a specific interest in public health genomics, a scientist with a specific interest in ethics of genetics a specialist in cancer genetics and three medical specialists in gastroenterology) and five group interviews (n with the target population of men and women aged 55 years. These group interviews were conducted using the Nominal Group Technique.28 During these interviews, participants were asked to rank a number of potential attributes from most to least important, and the mean group ranking of the attributes was then discussed in the group, after which participants could change their original individual ranking.28 Finally, four attributes were selected for this DCE (Table 1). The levels that were used to describe the identified attributes were based on realistic numbers representing the three most common types of genetic and familial CRC: Lynch syndrome, FAP, and FCC. About 3 of all CRC patients are diagnosed with Lynch syndrome.4, 29, 30, 31 Without surveillance, these patients have a 70 probability of developing CRC during their lifetime.4, 29, 30, 31 Patients who are diagnosed with Lynch syndrome are offered a preventive colonoscopy every 2 years. On average, their 5 year survival rate is 92 if they are aware of their genetic predisposition and participate in biannual colonoscopies.4, 29, 30, 31 FAP is present in 1 of all CRC patients.29, 30, 31 The probability of developing CRC among these patients is 99 without surveillance and therefore they are advised to undergo an annual colonoscopy.29, 30, 31 This results in a 5 year survival rate of 80 if CRC is discovered.29, 30, 31 Finally, FCC is considered to be present in 15 of all CRC patients.29, 30, 31 These patients have an at least 15 probability of developing CRC based on the number and age of relatives with CRC. Leonards, NSW, Australia) software was used to develop a D efficient design.26 The DCE consisted of nine unique choice tasks each containing two situations. Following each choice task, participants were asked whether they would actually participate in the chosen situation or not (ie, opt out). Before participants were asked to complete the choice tasks, they received detailed information on the meaning of all attributes and levels as well as an explanation on how to complete a choice task, illustrated by an example (see Supplementary File). The draft questionnaire was pilot tested among a subgroup (n of our target population. Four of these pilot tests were aloud tests, during which a researcher was present when the participant completed the questionnaire, reading out loud. It was tested by means of this pilot whether correct wording was used and whether the target population understood the attributes, levels and choice tasks. Additionally, the attribute level estimates that were retrieved from the pilot study served as input for the design of the final DCE questionnaire. QuestionnaireThe final questionnaire consisted of three parts. The first section of the questionnaire comprised 25 questions on demographics, such as gender, age, educational level, health literacy and ethnicity. Educational level was dichotomized into higher (ie, tertiary education) or lower education (ie, all other educational levels). Health literacy was measured by three validated Dutch questions of the Set of Brief Screening Questions.32 Participants scored these questions on a five point Likert scale, from zero to four. An average score of indicates inadequate health literacy, while an average score indicates adequate health literacy.32 Furthermore, questions pertained to information on experience with other national cancer screening programs, experience with genetic screening and family cancer history. Respondents were asked to indicate to what extent they agreed or disagreed with several theorems about their attitude, social norm, self efficacy and intention towards genetic screening for CRC. The second part of the questionnaire consisted of pandora wedding charms the actual DCE as explained above. The third part consisted of several theorems regarding the consequences of genetic testing, such as fear and worries, and on the possibility of incidental findings. Study populationFrom 2014 onwards, all Dutch residents aged 55 years will receive a biannual invitation to participate in the national population based screening program for CRC. Screening is carried out by means of the fecal immunochemical test. If the test result is positive, that is, blood is detected in the stool, a colonoscopy will be planned and participants are asked to complete a family cancer history questionnaire. At present, it is expected that genetic screening for CRC might only become part of the Dutch CRC screening program for individuals with a positive colonoscopy and a familial cancer history. As it was expected that preferences for genetic screening for CRC are highly dependent on age and experience with CRC screening, individuals were eligible to participate in our study if they were aged 55 years and had not yet participated in the CRC screening program or one of the extensive pilot studies that preceded the decision to implement the Dutch population based CRC screening. Respondents were recruited via an existing online panel of the general Dutch population. Respondents were selected to be representative for the entire target population with respect to age, gender and educational level. In total, 5500 individuals were invited to participate in this study and recruitment continued until at least 500 questionnaires were fully completed by a representative sample of the target population. The Dutch Central Committee on Research involving Human Subjects concluded that formal testing by an Institutional Review Board was not necessary, as respondents were only required to complete an anonymous and non invasive questionnaire once, which is in accordance with the Dutch legislation and guidelines laid down in the Declaration of Helsinki. Statistical analysisAll results were considered statistically significant when P All attributes were considered to be non linear and were recoded using effect codes.26 This coding procedure codes the reference category as and the sum of the effect coded attribute levels is always 0. Preferences for genetic screening for CRC Nlogit 5.0 (Econometric Software Inc, 2012, Plainview, NY, USA) was used to conduct the panel latent class models for this study. Such models account for the multilevel structure of our data (ie, every respondent answered nine choice tasks). Moreover, by means of such models, it can be determined whether preferences differ across unobserved subgroups of the population. This modelling procedure identifies whether there are within the data based on respondents answering patterns. Which respondents belong to what class is not assigned by researchers but is latent. Each respondent has a certain probability to belong to one of the identified classes. However, demographic characteristics can be incorporated into the modelling procedure, which provides insight into which respondents are more likely to belong to a certain class. Based on model fit tests (AIC, Log likelihood), it was tested which model was most suitable for our data and how many classes could be identified within the data. This resulted in a two class model based on the utility equation displayed below. The utility component (V) describes the utility that respondent belonging to class reported for alternative in choice task represents the constant of the model. Relative importance of the attributes The relative importance of the attributes was estimated separately for both classes of the panel latent class models. The difference between the highest and lowest attribute level estimate was calculated for each attribute. The largest difference value received an importance score of 1, representing the attribute that was deemed most important by respondents. The other difference values were divided by the largest difference value resulting in a relative distance between all other attributes and the most important attribute. Utility scores for Lynch syndrome, FAP and FCC screening For each of the three realistic screening scenarios, specific utility scores were calculated for both classes separately. The attribute levels that correspond with each of the three screening scenarios were entered into the utility function. The outcome (V) represents individuals willingness to participate in one screening initiative compared with the other initiatives. Top of pageResultsRespondents characteristicsOf the individuals initially invited (n 798 (14.5 respondents started the questionnaire within the first 4 weeks of data collection. Complete data was gathered for 532 eligible respondents (66.7 of those who started the questionnaire) and data collection was closed. Table 2 describes the demographic characteristics of the study population.

The majority of the respondents reported that genetic screening for CRC is important for themselves as well as for their family (Table 3). Although about half of the respondents expect to become seriously anxious and worried about developing CRC due to a suspected genetic predisposition, 89.0 reported that they would participate in genetic screening for CRC if such a program would become available (Table 3).


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