Reasons for low uptake of a psychological intervention offered to cancer survivors with elevated depressive symptoms

Abstract Objective In line with screening guidelines, cancer survivors were consecutively screened on depressive symptoms (as part of standard care), with those reporting elevated levels of symptoms offered psychological care as part of a trial. Because of the low uptake, no conclusions could be drawn about the interventions' efficacy. Given the trial set‐up (following screening guidelines and strict methodological quality criteria), we believe that this observational study reporting the flow of participation, reasons for and characteristics associated with nonparticipation, adds to the debate about the feasibility and efficiency of screening guidelines. Methods Two thousand six hundred eight medium‐ to long‐term cancer survivors were consecutively screened on depressive symptoms using the Patient Health Questionnaire‐9 (PHQ‐9). Those with moderate depressive symptoms (PHQ‐9 ≥ 10) were contacted and informed about the trial. Patient flow and reasons for nonparticipation were carefully monitored. Results One thousand thirty seven survivors (74.3%) returned the questionnaire, with 147 (7.6%) reporting moderate depressive symptoms. Of this group, 49 survivors (33.3%) were ineligible, including 26 survivors (17.7%) already receiving treatment and another 44 survivors (30.0%) reporting no need for treatment. Only 25 survivors (1.0%) participated in the trial. Conclusion Of the approached survivors for screening, only 1% was eligible and interested in receiving psychological care as part of our trial. Four reasons for nonparticipation were: nonresponse to screening, low levels of depressive symptoms, no need, or already receiving care. Our findings question whether to spend the limited resources in psycho‐oncological care on following screening guidelines and the efficiency of using consecutive screening for trial recruitment in cancer survivors.


| INTRODUCTION
Depressive symptoms are common in cancer patients, not only shortly after diagnosis or during active treatment but also in cancer survivors. 1,2 As effective psychological interventions exist to treat these symptoms, [3][4][5][6] clinical guidelines currently recommend to routinely screen cancer patients on distress throughout the illness and treatment trajectory in order to detect distress and refer patients accordingly to additional care. 7,8 These recommendations still hold, even though so far no well-conducted randomized control trials (RCTs) have demonstrated that mental health outcomes improve via these screening programs. 9 Evidence for the efficacy on interventions has mostly been confirmed in patients in the short-term phase and women with breast cancer, whereas less evidence is available for the efficacy of these interventions among cancer survivors. [3][4][5][6][10][11][12] Therefore, the Dutch Cancer Foundation released a call in 2013 for more evidence regarding the efficacy of psychological interventions among (nonbreast) cancer survivors. Following strict high-quality standards, 13 including consecutively screening on depressive symptoms, we set up a multicenter RCT examining the efficacy of cognitive behavioral therapy (CBT) and mindfulness-based cognitive therapy (MBCT) for treating depressive symptoms in cancer survivors. Because of the low trial participation, no conclusion could be drawn about the efficacy of the interventions. As a means to reflect on reasons why an RCT following high-quality methodological standards failed to work in clinical practice, this observational study examined the reasons for nonparticipation in the RCT and the demographic and medical characteristics of depressed survivors that did (not) participate. Cancer survivors in our trial were consecutively screened on depressive symptoms as a part of standard care, as recommended by the current clinical screening guidelines 7,8 and regarded as a quality standard in setting up an RCT. 14,15 Yet, the screening procedure was not efficient (ie, resulting in low uptake). Findings of our study may therefore add to the debate regarding the feasibility and efficiency of current screening guidelines for identifying patients in need for care. Our aim is twofold 1

| Participants
Eligibility criteria for being approached for screening were: a cancer diagnosis (except breast cancer), age between 18 to 75 years at the time of diagnosis, currently no active cancer, and completion of curative treatment 1 to 5 years ago. For trial participation, an additional eligibility criterion was the report of moderate levels of depressive symptoms (PHQ-9 ≥ 10). Exclusion criteria for trial participation were: not being able to read and write Dutch, having psychiatric comorbidity, receiving psychological treatment for depressive symptoms (currently or less than 2 months ago) and an instable antidepressant regimen (ie, starting/changing less than 2 months ago).

| Screening procedure
Individuals were routinely screened for depressive symptoms at departments radiotherapy, surgery, oral and maxillofacial surgery, gynecology, hematology, endocrinology, medical oncology, and colorectal surgery.
Individuals received a letter from their department inviting them to complete a mood questionnaire (PHQ-9) on paper or online and in case this score was elevated, they would be contacted. Individuals reporting elevated depressive symptoms (PHQ-9 ≥ 10) received feedback about their elevated levels and were informed that they would receive a telephone call to discuss the depressive symptoms and a possible need for psychological support. These telephonic interviews were executed by graduate clinical psychologists or research/student assistants who had received special training, in which they made a clinical assessment of the psychological problems. Subsequently, persons were selected on eligibility (using a standardized interview to check for exclusion criteria), interest in psychological support and willingness to participate. If this was the case, they received written information about the trial, a questionnaire, an informed consent form, and a prepaid return envelope.
They were asked to return a completed informed consent and questionnaire within 2 weeks. Individuals expressing interest in psychological support but who were ineligible or unwilling to participate were given advice to discuss their care needs with their medical specialist or general practitioner.

| Variables
For screening on depressive symptoms, the Patient Health Questionnaire-9 (PHQ-9) was used, 16 which is a self-report screening tool based on the nine depression criteria according to the Diagnostic and Statistical Manual of Mental Disorders. Each item can be scored from 0 (not at all) to 3 (nearly every day), resulting in total scores ranging from 0 to 27, with higher scores indicating more depressive symptoms. SPSS 25.0 was used for executing statistical analyses. Demographic (ie, age and gender) and cancer-related characteristics (ie, years since diagnosis, years since treatment, cancer type, treatment type and recurrence) were calculated. Chi-square tests and t-tests compared groups (ie, respondents versus nonrespondents; depressed versus not depressed; in trial versus not in trial) on demographic and cancer-related variables.

| RESULTS
Initially 2608 cancer survivors were invited to complete a screening questionnaire ( Figure 1). In total 25 individuals agreed to participate in the RCT, which was 1.0% of the approached individuals.
Of the 2608 cancer survivors approached for routine screening, 1937 returned a valid questionnaire. Those 1937 persons who returned the questionnaire were compared with those who did not return it. Compared with those who .0), more often male (61% versus 53%) and had more often a cancer recurrence (8.6% versus 4.8%). No significant differences were found in years since diagnosis or years since treatment. Concerning cancer site, highest response rates were found among survivors with bone and soft tissue (91.5%) and survivors with urological cancer (88.4%) with lowest response rates among lung cancer survivors (65.4%). A full overview regarding response rates and elevated depressive symptoms (PHQ-9 ≥ 10) according to demographic and cancerrelated characteristics can be found in the Appendix.
In total, 147 persons reported moderate levels of depressive symptoms (PHQ ≥ 10) and these persons were compared with those 1790 persons not depressed. Those depressed were significantly younger (63.7 ± 10.1 versus 59.3 ± 11.9) compared with those not depressed.
No significant differences between those survivors with or without moderate levels of depressive symptoms were found for gender, year since diagnosis, year since treatment, and cancer recurrence. Highest levels of depressive symptoms were found among lung cancer survivors (17.1%) and lowest levels of depressive symptoms among gastrointestinal cancer survivors (3.9%).

| DISCUSSION
As part of an RCT, we screened a large group of cancer survivors on depressive symptoms, with those reporting moderate or higher levels of depressive symptoms being contacted to discuss their need for care, and inform them about the possibility to receive psychological care, as part of an intervention study. We encountered a very low participation rate. The current paper examined the reasons for not participating, as we believe this will provide more insight into the feasibility of routinely screening for depressive symptoms in cancer survivors as well as of the use of consecutive screening for recruiting cancer survivors for a psychological RCT. Of the 2608 survivors approached, only 7.6% reported moderate levels of depressive symptoms, and of those, almost 50% reported no psychological care needs or already received treatment. One in four cancer survivors could not be screened on depressive symptoms, a response rate of 75% that can be considered high when using a survey 19 and which is also somewhat higher than response rates in other screening studies (varying from 63% to 68%) among cancer patients using surveys. [20][21][22][23] Research has shown that patients not responding to a screening questionnaire are also more likely to not show up for medical check-ups, suggesting that these patients may in general be difficult to reach. 24 An explanation for the nonresponse to screening may be the information given in the accompanied letter, using words like "depressive symptoms" and informing patients that they would be contacted in case an elevated score was reported (See Appendix Another factor that may explain variation in rates of depressive symptoms is the measurement of symptoms, which includes the use of a clinical diagnostic interview to classify major depressive disorder versus self-report screening questionnaires. 1,28 Although screening questionnaires are often used because of their convenience (ie, inexpensive and quick to administer to large groups), it should be noted that screening questionnaires overestimate the prevalence of depression. 28 In addition, variation in rates of depressive symptoms may not only be explained by using different screening instruments but also by using  1 Our study used the PHQ-9, which is commonly used in oncology for screening on depressive symptoms, 16,20,21 and using a cut-off of greater than or equal to 10, we found moderate levels of depressive symptoms rates of 7.6%. Other studies using the same criteria found similar, slightly higher percentages (9.3%-11.3%) for a mixed group of survivors. 20 also found low inclusion rates between 2.5% and 3.5%. 29,36 Abovementioned trials and our trial used consecutive sampling for patient recruitment, which encompasses systematically screening every individual who meets the selection criteria. 14 Another frequently used sampling method involves convenience sampling in which individuals are recruited by means of (self)referral, which has advantages in terms of cost, time, and logistics, but may produce an unrepresentative sample. 14 For this reason, consecutive sampling is generally seen as the golden standard and is favorable to convenience sampling, because the latter is more prone to selection bias. 14 However, in practice, this may not completely be the case, because a recent trial found that consecutive sampling still resulted in considerable selection bias in terms of enrolling predominantly young and highly educated patients. 29 Moreover, consecutive sampling is not mandated in the CONSORT guidelines (recommendations for high-quality reporting of RCTs in order to maintain high internal validity 39 ) implying that consecutive sampling is not a preferred method to convenience sampling for trial recruitment. Furthermore, convenience sampling may result in general in higher motivation among participants because of the self-referral method. 40 Given these considerations and our finding that most cancer survivors were not depressed and those that were did not want or already found help, it can be debated whether the methodological advantages of consecutive sampling outweigh its time and resource-consuming procedures. 40 We do not presume either consecutive or convenience sampling to be a superior method, but instead recommend that in the future the trial's aims and objectives should be decisive for choosing the appropriate sampling method.

| Study limitations
Findings of our study need to be set in the context of several limita- encounter other problems when filling in the questionnaire, you can also make use of the attached paper questionnaire and send this back using the prepaid return envelope (a stamp is not required).
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Results
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