Understanding the patient experience of chronic kidney disease stages 2–3b: a qualitative interview study with Kidney Disease Quality of Life (KDQOL-36) debrief

Qualitative concept elicitation interviews were conducted to develop a conceptual model capturing the signs/symptoms and impacts most relevant and important to patients with CKD stages 2–3b. The identified salient concepts were then mapped to the KDQOL-36 to evaluate the content validity of the KDQOL-36. New items were created for those salient concepts that did not have corresponding items within the KDQOL-36. The KDQOL-36 plus additional items were then tested by patients through cognitive debriefing interviews to find out whether they were relevant and clear for patients with CKD stages 2–3b. An overview of the study design is given in Fig. 1. This study has been reported following guidance provided by the Consolidated Criteria for Reporting Qualitative Studies (COREQ) checklist [38].

Patients were recruited with assistance from the patient recruitment agency Global Perspectives. Outreach techniques used included email, social media and physician contact. All potential participants provided informed consent online and then answered several screening questions to confirm their eligibility. The qualitative interview research protocol, interview guide, and all patient communication documents were reviewed by the New England Institutional Review Board for ethics compliance.

Eligible patients were aged 18 years or older, had a confirmed diagnosis of stage 2–3b CKD (based on patients returning confirmation of diagnosis forms completed by their treating physicians, or confirmation through medical records) and were not receiving dialysis treatment at the time of interview. Patients with a type 2 diabetes mellitus diagnosis could participate in the study but were to make up no more than 50% of the study population to ensure a range of CKD aetiologies were captured. A summary of patient eligibility criteria is given in Table 1. Patients were also asked to provide, where possible, their urine albumin to creatinine ratio and what medications/treatments they were receiving (diuretics, renin–angiotensin–aldosterone system blocking agents, angiotensin II receptor blockers [ARBs] and sodium-glucose co-transporter-2 [SGLT2] inhibitors).

Interviews were conducted by two interviewers (one male, one female; J. Maher [researcher, IQVIA], T. Casanas [market research consultant, independent]) who are trained and experienced in individual patient concept elicitation and cognitive debriefing interviews across a broad range of therapeutic areas. The interviews were the only contact the interviewers had with the interviewed patients. Patients were interviewed one-to-one over the telephone for 60 min following a semi-structured discussion guide. The interview approach used was in line with recommended guidelines provided by the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) Good Research Practices Task Force [18].

The patient interview guide was informed by a targeted literature review (TLR) previously performed to identify signs/symptoms and impacts on HRQoL experienced by patients with CKD across all stages and PRO instruments used in CKD [35]. The TLR was used to construct a preliminary conceptual model of the experience of patients with CKD overall, as well as patient subpopulations with differing CKD causes and severities, and complications of CKD [35].

As part of the interviews, patients were first asked a set of open-ended questions which allowed them to discuss the signs, symptoms and impacts of their CKD spontaneously. Next, the interviewer probed on concepts that were previously identified in the TLR. At this point patients were also asked to rate the bothersomeness of signs, symptoms and impacts they experienced. Bothersomeness was rated using a scale of 0–10 (0 being ‘not at all bothersome’ and 10 being ‘very bothersome’). For any ratings reported as a range (e.g. 6 or 7) or between integers (e.g. 6.5), the highest bothersomeness rating was recorded to capture the worst extent of concept bothersomeness. Within these questions, patients were asked about their first experience of the condition and what initially brought them to their doctor, how their experience may have changed over time, and current signs, symptoms and impacts of the condition and its treatments. Audio recordings of the patient interviews by IQVIA were transcribed verbatim by River Mist Transcription Services. Transcripts were anonymized prior to analysis.

Cognitive debriefing interviews were used to assess if patients found the PRO instrument items clear to understand and relevant to their disease experience. Patients were debriefed on 35/36 items from the KDQOL-36 (excluding the item related only to patients who were undergoing dialysis) and the additional items developed in the style of KDQOL-36 (including language used, response options and recall period) to address gaps identified in content coverage. Patients were asked to respond based on their experiences in the 4 weeks prior to being interviewed. The patients were asked to complete and evaluate the PRO items during the interview and give feedback on the items’ clarity and relevance to their CKD experience, the appropriateness of the recall period, and any concept they think had been omitted. Interview transcripts were anonymized and used to assess the clarity and relevance of the KDQOL-36 and any additional items.

A total of 31 patients were interviewed in this study. Twenty-two patients were interviewed for concept elicitation. The mean age was 58 years, over half were female (59%) and over four-fifths were white/Caucasian (86%). There was an even split between those diagnosed with CKD stages 2 and 3a (50%) and stage 3b (50%) and roughly a quarter (27%) were diagnosed with type 2 diabetes (Table 2).

Fifteen patients were interviewed for cognitive debriefing, including six who had taken part in the concept elicitation interviews. The mean age was 62 years, roughly half were female (53%) and almost all were white/Caucasian (93%). The majority were diagnosed with CKD stage 3a (13% stage 2, 60% stage 3a, 27% stage 3b) and a third (33%) had type 2 diabetes (Table 2). For both interview phases, patients were on a range of medications/treatments including angiotensin-converting enzyme inhibitors, ARBs, diuretics and SGLT2 inhibitors (Supplementary Table 1). As per the exclusion criteria, none of these patients were undergoing dialysis.

The interviews identified 56 concepts (33 signs/symptoms and 23 impacts), 17 of which had not been previously identified by the TLR [35]. All signs/symptoms and impacts were mentioned in the first three interview waves, with no new concepts identified in the final two interview waves, showing that concept saturation was achieved. Most concepts (85% [28/33] of signs symptoms and 74% [17/23] of impacts) were mentioned in the first wave. Inclusion of concepts reported as general negative emotional impacts was based on the patients’ own language when it was described as separate to depression or anxiety. Most newly reported signs/symptoms were related to the urinary system (increased urination, unusual urine colour/consistency, kidney infection). Ten of the twelve patients who reported increased urination (including nocturia) were receiving diuretics. Only one of those ten patients linked the symptom to their treatment and a further four patients receiving diuretics did not report increased urination.

Four signs/symptoms (‘fatigue/lack of energy/tiredness’, ‘sleep problems’, ‘increased urination [including nocturia]’ and ‘swelling in legs/ankles/feet’) and two impacts (‘anxiety/worry’ and ‘general negative emotional/mental impact’) were identified as salient. Example patient quotes included “Getting to sleep, waking up. Kind of a whole mixture of problems of not feeling well rested and feeling tired and dragging and not having enough energy to kind of falling asleep in the afternoon because my body's so tired and rested”, “Bubbles in urine – I think I worry about that. Well, that worries me because I don't know what it means”, and “But mental and emotional, that's definitely affected me. Because in the back of my mind I'm struggling. It's a major underlying health condition”. A further selection of patient quotes describing these concepts are given in Table 3. Of the salient signs/symptoms and impacts identified from patient interviews, three (50%) had not been identified in the previous TLR (‘increased urination [including nocturia]’, ‘swelling in legs/ankles/feet’ and ‘general negative emotional/mental impacts’) [35]. In addition, one sign/symptom (frailty/fractures) and two impacts (confusion and unable to self-care) reported in the previous TLR were not mentioned by the current patient population in the interviews [35]. The majority of signs/symptoms (29/33) and impacts (21/23) were reported as greater than 5 on the bothersomeness scale but were mentioned by less than 50% of patients. Several new concepts that were infrequently mentioned ranked highly on the bothersomeness scale, including three signs/symptoms (kidney infection, headache, and weakness) and three impacts (frustration/anger, fear, and body image issues). Some concepts had a broad range of bothersomeness scores reported. In the case of fatigue/lack of energy/tiredness, the average (mean) bothersomeness rating was 7.1 but patients reported scores ranging from 3 to 10.

The preliminary conceptual model of signs/symptoms and impacts from the previous TLR [35] was updated to integrate concepts identified in the 22 concept elicitation interviews for CKD stages 2–3b (Fig. 2). As well as highlighting six salient concepts during concept elicitation, the seventeen newly identified concepts (eight signs/symptoms and nine impacts) were added to the conceptual model. Several signs/symptoms and impacts from the preliminary conceptual model were revised to clarify or split/merge concepts to align with the patients’ interview responses. A summary of the conceptual model updates is given in Supplementary Table 2.

Minor differences were reported for both signs/symptoms and impacts by patients in both CKD groups stages 2/3a and 3b. Patients with stage 3b reported experiencing five symptoms not reported by patients with stage 2/3a, and stage 2/3a reported experiencing four symptoms not reported by patients with stage 3b (Supplementary Table 3). In addition, patients with stage 3b reported experiencing three impacts that were not reported by patients with stage 2/3a and patients with stage 2/3a reported five impacts that were not reported by patients with stage 3b (Supplementary Table 4). More signs/symptoms and impacts reported by patients with stages 2/3a met criteria for salience than those with stage 3b.

Three concepts identified as salient in the concept elicitation interviews were not covered by the KDQOL-36 (sleep problems, increased urination [including nocturia] and swelling in legs/ankles/feet). These three concepts were represented during cognitive debriefing interviews through four additional items in the style of the KDQOL-36: “During the past 4 weeks to what extent were you bothered by each of the following?” (The items were listed below the question: “Trouble falling asleep”; “Trouble staying asleep”; “Increased urination”; and “Swelling in legs/ankles/feet”). ‘Sleep problems’ was split into ‘trouble falling asleep’ and ‘trouble staying asleep’ based on patients reporting these separate issues when discussing sleep problems during cognitive debriefing (Table 3). The 35 items from the KDQOL-36 and the 4 additional items were considered relevant by all patients. Of the 35 items from the KDQOL-36, patients found 28 items (80%) clear, 6 items (17%) had minor comments around clarity and 1 item (3%) had a major comment around clarity. All patients found the four additional items to be clear, apart from one patient who thought it might be helpful to indicate that these items are also specifically relating to a patient’s CKD rather than general health. Three patients also reported it being unclear whether items 17–25 (including muscular soreness, chest pains, dry skin and faintness) were related specifically to their CKD and were not in general or due to another disease. Item 28 (relating to the impact of CKD on fluid restriction) caused the most significant confusion among patients because four patients misunderstood it as ‘fluid retention’ and an additional patient reported initially reading it as ‘fluid retention’ before re-reading and understanding what the question meant. Almost all (95%) of the KDQOL-36 items (that is, 35 of the 36 original KDQOL-36 items plus the 4 additional items identified in the current study) were considered by patients to have an appropriate recall period of 4 weeks. This was considered too short for two items (Item 1: ‘In general would you say your health is’ and Item 4: ‘Accomplished less than you would like’) by two patients who proposed a 3-month recall period instead. Four patients commented on five items in the KDQOL-36 based on the Covid-19 global pandemic, which was ongoing at the time of the interviews. Of these, two items related to social interactions and travel, which had been reduced during the global restrictions, one related to ability to work and two related to physical and mental health. The patients reported that these questions were relevant and clear and would be so during ‘normal’ times. Of the interviewed patients, ten suggested twelve concepts that could potentially be added. However, those raised were already covered either during concept elicitation interviews and not identified as salient or by existing items in the KDQOL-36.

By focusing on disease stages 2–3b the conceptual model is restricted to a portion of the CKD population and so does not develop our understanding of the whole CKD experience, making the study more applicable to early-stage disease. The study population was also skewed towards white/Caucasian patients, with a limited representation of other ethnicities. Some of the concepts recorded by patients could have been comorbidities that were incorrectly attributed to CKD; however, inclusion of the measure of salience should minimize the risk of such anomalies being emphasized in the conceptual model. Finally, during cognitive debriefing there was a disparity between the number of patients recruited with stages 2–3a (73%) and stage 3b (33%). This could have influenced the results indicating suitability of the KDQOL-36 plus additional items for the earlier stages.