Thirty-eight patients were recruited for the concept elicitation study. Forty subjects were scheduled; however, two subjects did not show. One subject left mid-focus group session due to discomfort in the group setting (he was the only male in the group of four); his data, up to the point of his departure, was deemed useful to include in the analysis (the subject also completed the demographic and health information form via mail). Twenty-six women (68%) and 12 men (32%) participated in the concept elicitation interviews. Seventy-six percent of the subjects were Caucasian, and all patients had a high school education or its equivalent. Fifteen subjects were diagnosed with severe, eight with moderate, and seven with mild depression; eight subjects were in remission.
Twenty patients participated in the CIs; their ages ranged from 26 to 74, with a mean age of 44 (standard deviation [SD] = 13.5). Most patients were female (n = 17, 85%) and Caucasian (n = 13, 65%). Eight patients (40%) were working full- or part-time. Two patients were diagnosed with severe, seven with moderate, and seven with mild depression; four patients were in remission. See Table for a more detailed description of the demographic details for the focus groups and CIs and Table for detailed information about their health status.
Summary of Subjects' Socio-demographic Information
Summary of Subjects' Health Information
Concepts elicited and development of MDD PRO
Sixty seven (67) distinct concepts were elicited, analyzed, and merged based on conceptual equivalence (e.g., anxiety and panic) and clinical validity (e.g., obsessive and negative thoughts). The final list included 35 concepts that were grouped into 11 general domains. These included: i) emotional (11 concepts such as angry and helpless), ii) cognitive (six concepts including memory and clarity of thought), iii) motivation, iv) work, v) sleep (three concepts), vi) appetite (two concepts), vii) social (four concepts), viii) activities of daily living (two concepts), ix) tired/fatigue, x) body pain, and xi) suicidality (three concepts). All concepts but three (i.e., engage in intimacy, ability to articulate, and clear-headed) were saturated. Items were generated to reflect each of the 35 concepts. These concepts resulted in 15 daily and 20 weekly items, (i.e., recall periods of the "past 24 hours" and "past seven days," respectively). Thirty-two items used an 11-point severity or frequency numerical rating scale response format. One item asked for the number of hours of sleep in the past 24 hours, and one item asked, "How would you rate the amount of sleep you had in the past twenty-four hours?" with the responses, "less than I would have liked," "about the right amount," and "more than I would have liked." One item asked "How would you rate the amount you have eaten in the past twenty-four hours?" with responses, "less than I would have liked," "about the right amount," or "more than I would have liked."
Four of the most frequent concepts reported were "avoidant" (n = 34), "self-image/confidence" (n = 30), "thoughts of death" (n = 25) and "suicidal ideation" (n = 25). Subjects across all severity groups avoided others when depressed. Subjects used the words, "isolate," "tune out," "not a people person," "hide from the world," "shut people out," "shut down," "alienation," "world gets smaller," "avoidance," "hibernated state," "solitaire [sic]," and "withdrawn." Subjects described the need to avoid others in the following ways:
"I shut everybody out. I pick up my book, my book goes in front of my face, and I don't want to hear anybody, don't talk to me... Leave me alone and let me live in my own little world for now. And that's what I do when I shut down" (severe).
I actually isolate myself. I isolate myself. I become very withdrawn. I don't leave. I don't interact. I don't want to go out. I don't want to deal with anyone (mild).
When discussing their avoidance, subjects described themselves as avoiding people or situations, hiding, sleeping, or staying in bed, avoiding self-care, avoiding emotions, feeling safe at home, and losing communication with people, saying, for example:
It's a very dark place... You do fall out of communication with people and you just kind of sit in bed and lack the willpower to really get out there and do what you need to do (moderate).
When describing a worst day with depression, subjects indicated their need to be left alone, to avoid any interactions or situations prompting interaction ("picking up the phone,"). One patient, for example, reported that when depressed:
"I don't feel like getting out of bed and facing the world. I don't feel like eating, I feel like burying my head in the sand like an ostrich. And I just don't feel like - I'm just nervous around people. I don't want to be around them" (remission).
Subjects were candid about suicide. Nine subjects in three severe groups, both moderate groups, and one each of the mild and remission groups discussed their experiences with suicide attempts, describing the various methods attempted (e.g., wrist cutting, swallowing pills, hanging self). At the time of their suicide attempt, patients saw death as their "only option," saying, for example, "At those times it just... seem like there was no way out" (mild) and "I finally decided that I just wanted to give up, and I tried to take my life (severe).
MDD is described by subjects as a constellation of symptoms, including depressed mood (e.g., feeling sad), and impacts. The complex, cluster-like presentation of MDD became evident through subjects' descriptions of symptoms as impacts and vice versa (e.g., decreased concentration as a symptom and/or impact of MDD). Following the analysis of the transcripts from the focus groups, the comprehensive list of symptoms and impacts spontaneously mentioned by subjects with MDD was reviewed and organized into a conceptual framework (available upon request). A draft patient-completed instrument was developed to assess the symptoms and functional impairments associated with MDD. While there are currently several clinician-completed tools for diagnosis and management of MDD, few, if any, capture the patients' perspective.
Cognitive interviews of the MDD PRO
The first round of CIs of the 35-item questionnaire found the items understandable, relevant, and readable on the whole across severity groups. Several patients commented on the difficulty of using a 24-hour recall period for concepts such as avoiding other people and those which involved activities that may not occur every day. Some items were changed from daily to weekly items due to patient input that the symptom required a longer recall period to capture variation and frequency. This resulted in development of a daily and weekly PRO questionnaire. Because both a daily and a weekly recall period were tested, patients were specifically asked about the appropriateness of the recall period for each concept presented. The choice of placing an item into the daily or weekly questionnaire was a direct result of the patients' preference (relevance to day-to-day life) and ability to recall changes which may occur with each concept over 24 hours or seven days.
The results of the second round of interviews were similar to the first in terms of understandability, relevance, and readability, with added feedback regarding the questions related to sleep and appetite changes. The results of the third round of interviews were similar to previous rounds, with few changes suggested except for changing some daily items to weekly recall. Patients did suggest, for example, that the item regarding losing interest in just about everything be changed to be more specific (i.e., losing interest in just about all activities) and that the recall period be changed from daily to weekly for this item. For example, one patient stated, "Well, I guess lost interest in just about everything - I'm just trying to think about what everything would be. I guess I just was a little confused at that." Another patient indicated this question was difficult to answer because "... I think it takes more than 24 hours to just lose interest in everything." The 11-point NRS, instructions, and recall period were confirmed in the last set of CIs.
Patients experienced and recognized the emotional concepts (irritability, lack of pleasure, helplessness, anger, crying, sadness, feeling overwhelmed, hopelessness, guilt, lethargy, and anxiety), and felt they were well represented in the questionnaires. Specific probing indicated that although patients defined "helpless" and "hopeless" differently, their initial presentation as adjacent items led to some confusion; moving the items further apart eliminated the confusion between the two words. The concept of "lack of pleasure" was tried in a number of item formats, with one item "how much of the time have you felt that you did not enjoy activities that you used to like to do?" being chosen as the most preferred wording. Other suggestions for wording were incorporated in order to use patient words as much as possible.
The cognitive concepts (negative perceptions/thoughts, problems with concentration/focus, memory problems, clarity of thought, indecisiveness, and lack of confidence) were also commonly experienced by patients and accepted as important to the questionnaires. Specific wording from patients helped to clarify the item on negative thoughts, with "dwell on the negative" being well accepted and understood to represent the concept. Suggestions for parenthetical examples for the concentration and memory items were made by patients, and the changes were confirmed by later CIs and led to patients interpreting the items as intended.
The concepts of changes in eating and sleeping proved more difficult to approach in the versions of the questionnaire tested, since different patients can have different presentations, with either increased or decreased sleeping or eating.
In summary, all daily items were changed after Round 1 to include the phrase, "In the past twenty-four hours," at the beginning of the question rather than the end to focus attention on the recall period; likewise all weekly items were also revised to include the phrase "In the past 7 days" at the beginning of the question. Instructions were changed after Rounds 1 and 2 to indicate the correct number of items in the questionnaire as items were deleted. Six questions were moved from the daily to the weekly recall period as patients' reports indicated this recall was more appropriate. Other changes were relatively minor, such as rephrasing sentence wording to more accurately reflect patients' experience or patients' words. For example, "In the past 7 days, how difficult has it been for you to interact with close relatives?" was changed to, "In the past 7 days, how difficult has it been for you to interact with close family members?" and "energetic" was changed to "lack of energy." In addition, the order of some items was changed, such as moving the items "helpless" and "hopeless" further apart in the questionnaire after patient input suggested their proximity may be lead to confusion between the terms. Finally, separate questions on "increases" and "decreases" in appetite and sleep were created instead of using "changes" in appetite or sleep.