Introduction 1 2 3 4 5 6 5 7 8 9 Patients and methods Ethics approval and informed consent The Ethics Committee of the Erasmus MC approved the research protocol. All participants gave additional written informed consent to be interviewed for the study. Parent study 9 Respondents n n Assessing response shift 1 5 2 2 2 3 4 10 11 As a novel method to assess response shift we used vignettes that each described a health state relating to side effects of therapy for localized prostate cancer, i.e. urinary, bowel or erectile dysfunction. The vignettes contained items of the EQ-5D self-classifier complemented with items on dysfunction, for instance, ‘Mr. A has no problems in walking about, has no problems washing or dressing himself, experiences urinary leakage daily, has no pain or discomfort, is not anxious or depressed’. Respondents were asked to indicate how good or bad they evaluated these health states on visual analog scales anchored at the lower end (0) by ‘very bad’ and at the upper end (10) by ‘very good’. We used the vignettes to explore reprioritization. We hypothesized that men would value the health states as less detrimental after diagnosis than before. After diagnosis they knew they might experience these dysfunctions themselves in the context of prostate cancer treatment. Fig. 1 Study scheme  Fig. 2 Original and then-test scores of the EuroQol valuation of own health by prostate cancer patients (n = 52)  Fig. 3 Original and then-test scores of the SF-36 mental health by prostate cancer patients (n = 52).  2  Fig. 4 Original and then-test scores of the SF-36 vitality by prostate cancer patients (n = 52). 2  Statistical analysis 12 t P d d d 6 13 t Results 1 n n n n n 1 Table 1 n  n n n  Radical prostatectomy 18 7 25 External radiotherapy 1 2 3 Brachytherapy 13  13 Active surveillance 9  9 Hormonal treatment   1 1 No treatment choice yet 1  1 2 2 Table 2 n Referring to n P- Thentests n P Effect size: thentest vs original  n P Effect size: thentest vs. original 2 months pre-diagnosis EuroQol own health 80.2 (11.7)  83.2 (9.0) 0.058 −0.26 85.2 (7.6) a −0.43 SF-36 mental health 83.2 (11.6)  84.5 (11.0) 0.304 −0.10 83.2 (10.9) 1.00 0.01 SF-36 vitality 75.3 (15.6)  79.6 (12.0) 0.008 −0.28 79.4 (12.4) 0.046 −0.26 1 month post-diagnosis, before initiation of treatment EuroQol own health 74.5 (15.1) 0.010    74.1 (14.5) 0.618 0.03 SF-36 mental health 75.8 (16.8) a    72.8 (18.3) 0.042 0.17 SF-36 vitality 74.7 (14.2) 0.771    72.6 (13.7) 0.111 0.15 7 months post-diagnosis, after intiation of treatment in 80% of respondents EuroQol own health 77.6 (13.7) 0.196       SF-36 mental health 80.4 (13.8) 0.066       SF-36 vitality 73.1 (17.7) 0.213       P- P  a 2 4 2 P 3 3 Table 3 P Health state description n n P- Effect size pre-diagnosis vs. 1 month post-diagnosis n P Effect size pre-diagnosis vs. 7 months post-diagnosis Daily urinary leakage 5.6 (2.1) a 0.038 −0.32 5.9 (1.5) 0.348 −0.14 Daily bowel cramps 5.3 (2.0) 6.0 (1.6)  0.011 −0.41 a 0.012 −0.39 Serious erectile dysfunction 5.3 (2.2) a <0.001 −0.57 a 0.005 −0.47 a The results of the then-test were significant in 4 out of 9 comparisons, the results of the vignettes in 5 out of 6. The overall type I error rate, which is the ratio of significant findings to the number of comparisons, was 0.6 (9 out of 15). Non-response analysis n Discussion Men diagnosed with prostate cancer evaluated their pre-diagnosis health in retrospect as better than at the reference point itself. Post-diagnosis–pre-treatment health was rated worse in retrospect than at the reference point. This suggests that ‘true’ changes in health between the first assessment before diagnosis and the second one at 1 month post-diagnosis were larger than the original scores disclosed, and that  response shifts were induced by first, the diagnosis, and second, subsequent treatment. The sizes of the response shifts induced by the diagnosis were larger than those induced by the treatment. The negligible to small effect sizes indicated that only some recalibration occurred. The directions of the effect sizes were interpretable and consistent with our hypotheses. Additionally, men evaluated vignettes relating to side effects of prostate cancer treatment as less detrimental after they were diagnosed than before diagnosis. We interpreted this change as a reprioritization of respondents who became aware after being diagnosed with prostate cancer that they were at risk of experiencing these health states themselves as a consequence of being treated for prostate cancer. In this new context dysfunctional health states were evaluated as less bad than before. The effect sizes were moderate for erectile dysfunction and small in the two other ones, indicating that reprioritization also occurred. The directions of the effect sizes were interpretable and consistent with our hypotheses. The overall type I error rate was 0.6, which indicated that the statistical significance is very unlikely to be caused by chance. This is an additional indication that our findings reflect real differences. We conclude that the results of the then-tests and the ratings of the vignettes both indicate the presence of a response shift and adaptation of the patients to their new situation. 5 14 2 14 15 16 8 17 18 19 20 The present study has several strengths and limitations. The study design is one of its strengths; the unique context of the ERSPC enabled the inclusion of respondents before they (or anyone else) were aware that they had prostate cancer, which is usually unfeasible. To our knowledge this is the first study to measure response shift in men who were diagnosed with cancer. An additional strength is the compliance of the respondents; 51 of the 52 respondents completed the 7-month assessment. For the then-test we selected measures that are considered subjective (i.e. SF-36 mental health and vitality, and EQ-5D of own health) but no objective items, which can be considered a drawback of the study. Furthermore, we acknowledge that offering questionnaires in two different modes (self-administered questionnaires before diagnosis vs. telephone interviews afterwards) may have been less than optimal. This design was chosen based on practical considerations, because assessments by telephone in 3,892 screen participants was not feasible, and self-administered questionnaires at 1 month after diagnosis undesirable since we wanted these assessments to be completed before the initiation of treatment. The unavailability of information on marital status and education is also a drawback. Another potential limitation of our study is that the interval between the initiation of treatment and the assessment at 7-months post-diagnosis was not the same for all respondents; it is possible that response shift may vary according to the length of time that elapsed since treatment. However, information on this interval had been of limited use. The most common therapies for localized prostate cancer nowadays are surgery, radiotherapy, and active surveillance. These therapies differ greatly (by nature) in duration, the onset of side effects and their course over time. It may be that particular groups may be more prone to response shift than others, e.g. depending on age or prognosis. We plan to address this issue further, preferably in a larger sample than used in the current study. Conclusions Using two complementary techniques we found that a diagnosis of prostate cancer induces response shift. From a methodology point of view, the vignette-method needs to be explored further.