Content Validation of the ATTR Amyloidosis Patient Symptom Survey: Findings from Patient and Clinician Cognitive Debriefing Interviews

Figures & data

Figure 1 Development of ATTR-PSS.

Figure 2 Content included in clinician and patient cognitive debriefing interviews.

Table 1 Demographic Characteristics of Clinicians Who Participated in Cognitive Debriefing Interviews

	ATTR-PSS Cognitive Debriefing: Clinicians (N=7)
	N	%*
Primary practice type
Haematology/Oncology	5	71%
Neurology	1	14%
Cardio-Oncology	1	14%
Gender
Female	3	43%
Male	4	57%
Region of residence/practice
Northeast, US	1	14%
Southeast, US	1	14%
Midwest, US	4	57%
Europe	1	14%
Number of years in practice
5–10 years	3	43%
11–20 years	1	14%
≥21 years	3	43%
	Mean, %	Range
Number of patients treated
with ATTR amyloidosis	67	30–100
with hATTR^ǂ	25, 38%	7–60
with wtATTR^ǂ	36, 61%	15–70

Notes: *Percentages may not sum to 100% due to rounding. ^ǂPercentage calculated out of all treated patients with ATTR amyloidosis.

Abbreviations: ATTR-PSS, amyloid transthyretin amyloidosis patient symptom survey; hATTR, hereditary ATTR amyloidosis; wtATTR, wild-type ATTR amyloidosis.

Table 2 Overview of Results from Clinician Cognitive Debriefing

Element of ATTR-PSS	Representative Clinician Quote
Length of survey	I think it’s a very appropriate length. This is not overwhelming. I think it’s good. Again, it’s all the symptoms that patients experience. I think it’s good.
Breadth of survey content	I think it will get really important information that has not previously been captured regularly in this patient population. I think we will learn new things about the extent of their autonomic failure and the symptomatic cardiac failure that they are having. This is a very good … I think it will be important to be included with patients who are on therapy.
Instructions	In my facilities, we have had situations where owing to illiteracy we have had caregivers complete the questions and there have been situations where the caregiver would read out the question and the patient would say something, but then the caregiver would say, “No. I noted when you were short of breath most of the time and not just sometimes.” … They are the ones completing it for the patient. Again, this might be an anecdote and not really an issue, but it’s something that I have experienced.
Symptom list	I think it’s good and it’s very relevant to the patients. Again, a lot of the research in this field has struggled with how to assess these types of things in these patients. Amyloid is a very different disease from everything else that clinical trials have been done in, and so there’s a lot of difficulty in figuring out what we should be assessing. This is a good global assessment of what patients are feeling and I think that’s valuable.
	Fatigue is a big one. The heart failure symptoms. Anything with shortness of breath, dizziness, edema. The pain ones are very important. Then the nutrition one. The GI symptoms. Yes, it’s gotten them all.
Clarity of symptoms	Some of the symptoms, like dementia, I do not know necessarily the patients can quantify that as rarely, sometimes, most of the time, all the time. Dementia is more of a medical diagnosis the same as sleep apnea. Again, malnutrition is another one that stands out … That they are rarely malnourished or most of the time malnourished. Those seem like more as clinical diagnoses more than symptom of patient and you are trying to get patient symptoms. I recommend you being more specific. What it is that you are trying to get from patients.
	I would say, “Can you feel hot and cold?” What I actually ask patients is, “You put your foot into a hot bathtub, can you tell you're at risk of burning yourself?” You have to tell the temperature of the bathtub by your hand because you cannot dip your toe and know.

Table 3 Demographic Characteristics of Patients Who Participated in Cognitive Debriefing Interviews

	ATTR-PSS Cognitive Debriefing: Patients (N=10)
	n	%
Gender
Female	5	50%
Male	5	50%
Age range
<50	0	0%
50–54	2	20%
55–59	4	40%
60–64	1	10%
65–69	2	20%
≥70	1	10%
Type of ATTR
hATTR with CM	2	20%
hATTR with PN	4	40%
hATTR with CM & PN	2	20%
wtATTR	2	20%
	Mean	Range
Time since diagnosis	2.38 years	<2 months to >5 years

Abbreviations: ATTR-PSS, amyloid transthyretin amyloidosis patient symptom survey; CM, cardiomyopathy; hATTR, hereditary ATTR amyloidosis; PN, peripheral neuropathy; wtATTR, wild-type ATTR amyloidosis.

Table 4 Overview of Results from Patient Cognitive Debriefing

Element of ATTR-PSS	Representative Patient Quote
Length of survey	I did not find it too long at all because it’s something that I could walk through fairly quickly. Again, you are talking about your own symptoms. I know what I feel. I know what’s happening to me. It’s not some kind of nebulous question out there. (female, hATTR)
Breadth of survey content	Because these are actual items that are related to the condition and you want to get a full understanding of what the patient has and does not have … I think the survey is good because had I known that these symptoms attributed to amyloidosis, I would’ve been more aware, or trying to figure it out sooner. (female, hATTR)
Instructions	I cannot curl the same dumbbell at 80 that I could at 75, but I am not sure that’s related to amyloidosis as it is to just old age … Erectile dysfunction or other sexual dysfunction … Again, I cannot differentiate between old age and amyloidosis … In other words, I do not want to attribute it to amyloidosis, when again age is a factor. (male, wtATTR)
Item text	Interviewer: Then there is a line that says, “Please select up to five symptoms” which I had indicated that you chose seven. I am not sure if you saw … Patient: (Laughs). I did not even read that. Interviewer: That’s what I thought. You missed it. Patient: Mm-hmm (affirmative). Yes. We need to put that next to the question. Interviewer: Move it up a line? Patient: Yes, because I went right by that. (female, hATTR)
Clarity of symptoms	Pain “Pain,” that is extremely broad and what the heck does that mean, because it’s not associated with any one particular thing there, just pain. That’s an odd question. In the past month have I experienced pain? I am irritated by the question. Sorry, I keep thinking, “That's entirely too broad. What does pain mean?” If it was pain that was associated with one particular thing it would be easy. And, also … I think psychological pain. So, I am like, “What is this?” (female, hATTR)
	Sexual dysfunction You could probably break it up for women and men because, men with erectile would apply and the second part would be for the ladies. I have got pain and dryness, so you may want to separate it out for men and women … Because I had to think about it. The first part does not apply to me, the second part, yes, that does. (female, hATTR)
	Pain, numbness, or tingling in feet or legs … pain, numbness, or tingling in your feet or legs. I am going to put most of the time for me. I think that’s a good question. The doctor seems to ask that quite a bit, as well, with the disease, so pretty self-explanatory. Then qualifying it in the feet or legs is good because I think there are other parts, too, that maybe have some. (male, hATTR)

Table 5 ATTR-PSS Survey Items

Item Stem	Item Content	Response Options
In the past month, how often have you experienced each of the following symptoms related to ATTR amyloidosis?	32 symptoms	5-point Likert scales ranging from “Never” to “All of the time”
In the past month, how severe were each of the following symptoms related to ATTR amyloidosis?	32 symptoms	5-point Likert scales ranging from “Not at all” to “Very severe”
Of all the symptoms you have experienced due to ATTR amyloidosis in the past month, which symptoms have had the most significant impact on your daily life? Please select up to 5 symptoms.	32 symptoms	Checkboxes
Overall, how severe were your ATTR amyloidosis symptoms in the past month?	—	5-point Likert scale ranging from “Not at all” to “Very severe”
Has a doctor ever diagnosed you with:	11 medical conditions	“Yes,” “No”
In the past year, have you lost or gained 10 pounds or more when you were not trying to?	—	“Yes,” “No”

Figure 3 Modifications to ATTR-PSS symptom list. Conditions listed in “medical diagnoses” and “other” categories were originally included as part the symptom list. At the suggestion of clinicians, these conditions were removed from the symptom list and added as 2 new items to the ATTR-PSS (as represented by the * symbol). Revised symptoms (represented by the * and ^§ symbols) were modified for language/clarity; the updated language is reflected in the figure.