Targeted Literature Review
A schematic diagram reporting the results of the TLR is outlined in Figure 2. A total of 972 published abstracts on oncology treatment include PROs screened for patient experience and satisfaction concepts of patient expectation, convenience, satisfaction with medication, and adherence and tolerability to therapy. After removing duplicates, publications with only abstracts available, reviews, cases studies, or clinical guidance articles, 406 full-text articles were reviewed and assessed for eligibility. Of these, only 23 articles were deemed eligible, as they included oncology trials assessing medication interventions, PROs measureing treatment or medication convenience, tolerability, or satisfaction.
Following the literature review, a brief gap analysis was conducted on the 28 satisfaction-related questionnaires identified from the literature and key informationInstrument concepts were reviewed and mapped to concepts of interest and the specific context of use in cancer trials: convenience of medication dosing schedule, medication satisfaction, and satisfaction with mode of treatment administration. Of these 28 measures, only four were specifically related to cancer/chronic illnesses, and encompassed patient satisfaction with oncology treatment: Cancer Therapy Satisfaction Questionnaire (CTSQ) [27], Treatment Satisfaction Questionnaire for Medication (TSQM) [28], FACIT-Treatment Satisfaction-General (FACIT-TS-G), and Treatment Satisfaction with Medicines Questionnaire (SATMED-Q) [29].
Based on the review of the four identified PROs with potential concepts of interest, none were deemed suitable to assess the treatment and medication experience and satisfaction of patients with RRMM. Instead these tools included multiple domains, including satisfaction with healthcare procedures, quality metrics, information perception by patients, healthcare provider (HCP) appraisal, and provider ability to provide adequate care. Additionally, existing measures did not look at the indirect difference between once-weekly versus twice-weekly administration of an infusion-administered oncology treatment. Infusion-administered oncology treatments require patients to come back to the clinic, and would require customized step-up dose escalation, which may be forgotten or omitted.
Based on this finding, the study team decided to create a new instrument specifically for use with RRMM therapies [17] in order to more accurately capture experience, convenience, and satisfaction with the current once-weekly administration of RRMM treatment.
Development of Preliminary Conceptual Framework
An item pool of relevant items from the four identified PROs was created for potential adaptation and inclusion in the new measure. Items were revised to capture treatment experience, satisfaction, and convenience; and a preliminary CF was developed to include the RRMM treatment COIs of patient experience. Patients’ experience and satisfaction with treatment efficacy and safety were posited to be directly related to the experience of improving or worsening symptoms, side effects, patient adherence to treatment, and the overall burden on the patient imposed by factors such as the convenience of schedule, duration, timing of dosing, and treatment cost.
Results from Nurse Focus Group
Five RNs were recruited to participate in an online focus group. Two RNs were unable to participate at the last minute. The three participating RNs reported treating an average of 22 patients with MM per week, of which 33% were patients with RRMM. Oncology nurses described patients’ satisfaction and tolerability with RRMM treatment based on their clinical practice experience. Primarily, nurses reported that patients with RRMM derived satisfaction from experiencing a treatment response or indication that the treatment was working, and from good communication with their cancer care team. The nurses stated that patients were willing to tolerate treatment side effects if they saw a treatment response or if their QoL was not significantly impacted.
Draft Preliminary SEQ-MM v0.1 Tool
Based on the additional information from the RN focus groups, the SEQ-MM v0.1 was finalized before patient testing. Fourteen items included the following domains: convenience (n=3), interference (n=5), satisfaction (n=1), tolerability (n=1), preference (n=1), experience (n=2), and confidence (n=1). Readability of health-related measures is a core component of comprehensibility [20, 30, 31]. Using the Flesch-Kincaid Grade Level (FKGL) test, the grade level of the SEQ-MM v0.1 was evaluated to grade 8.4.
Concept Elicitation Results
Three rounds of hybrid concept elicitation and cognitive interview focus groups were conducted to support attainment of concept saturation.
Patient Characteristics
The detailed demographics of the patient sample are reported in Table 1a. Ten RRMM study participants participated in three focus groups and one individual interview. Three rounds of focus group discussions and one interview were conducted. Five participants were in each round (Round 1: two focus groups; Round 2: one focus group and one interview). Participants were primarily male (70%), with mean ages of 56±8 years.
Table 1a
Patient Sociodemographic Characteristics
Characteristics
|
Total (N=10)
|
Age
|
|
Mean (SD), Median [Range]
|
56 (8), 54 [47-71]
|
Gender, (%)
|
|
Male
|
7 (70%)
|
Ethnicity, n (%)
|
|
Hispanic or Latino
|
1 (10%)
|
Not Hispanic or Latino
|
9 (90%)
|
Racial Background, n (%)
|
|
Black or African American
|
1 (10%)
|
White
|
9 (90%)
|
Employment Status, n (%)ϯ
|
|
Employed, full-time
|
5 (50%)
|
Employed, part-time
|
1 (10%)
|
Unemployed
|
2 (20%)
|
Retired
|
1 (10%)
|
Disabled
|
2 (20%)
|
Highest Level of Education, n (%)
|
|
Some college
|
1 (10%)
|
College degree
|
7 (70%)
|
Post graduate degree
|
2 (20%)
|
Insurance Status, n (%)
|
|
Insured, minimal out-of-pocket costs
|
7 (70%)
|
Insured, significant out-of-pocket costs
|
3 (30%)
|
ϯ Responses not mutually exclusive
|
Half of participants reported receiving their cancer diagnosis over three years prior to screening (n=5, 50%). Most RRMM treatments were received subcutaneously (n=7, 70%), and the majority reported receiving lenalidomide (n=8, 80%), dexamethasone (n=7, 70%), or bortezomib (n=6, 60%). Most participants were insured and paid minimal out-of-pocket costs (n=7, 70%). Detailed medical information is reported in Table 1b.
Table 1b
Medical History
Health Characteristic
|
Total (N=10)
|
How many years ago did you receive the multiple myeloma diagnosis?
|
|
1 - 2 years
|
2 (20%)
|
2 - 3 years
|
2 (20%)
|
3+ years
|
5 (50%)
|
Missing
|
1 (10%)
|
Has your cancer spread to another region or organ? Yes
|
4 (40%)
|
Are you currently receiving treatment? Yes
|
10 (100%)
|
Can you recall the name of the treatment you are taking/you received?ϯ
|
|
Kyprolis® (carfilzomib)
|
2 (20%)
|
Velcade® (bortezomib)
|
6 (60%)
|
Ninlaro® (ixazomib)
|
2 (20%)
|
Revlimid® (lenalidomide)
|
8 (80%)
|
Pomalyst® (pomalidomide)
|
3 (30%)
|
Synovir®, Thalomid® (thalidomide)
|
1 (10%)
|
Empliciti® (elotuzumab)
|
1 (10%)
|
Cytoxan®, Neosar® (cyclophosphamide)
|
1 (10%)
|
Prednisone
|
2 (20%)
|
Dexamethasone
|
7 (70%)
|
Others (Please specify)*
|
3 (30%)
|
What date was your last RRMM treatment?
|
|
<6 months
|
7 (70%)
|
6 months - 1 year
|
1 (10%)
|
1 - 2 years
|
1 (10%)
|
Missing
|
1 (10%)
|
How is/was your RRMM treatment administered?
|
|
Subcutaneous (SC)
|
7 (70%)
|
Intravenous (IV)
|
3 (30%)
|
Have you been diagnosed by a medical doctor with any other serious health conditions besides your cancer?
|
|
No other health condition
|
7 (70%)
|
Kidney disease
|
2 (20%)
|
Other serious health condition†
|
1 (10%)
|
In general, how would you say your health was within the past week?
|
|
Very good
|
6 (60%)
|
Good
|
3 (30%)
|
Fair
|
1 (10%)
|
ϯ Responses not mutually exclusive
* Other treatment includes: Daralex, Daratumumab, Veneloclax
† Other serious condition include: High Blood Pressure
|
Experiences with Treatment
Generally, participants relayed positive experiences with treatment—knowing their treatment is working (n=8, 80%), not experiencing side effects (n=7, 70%), having a good relationship with their HCP (n=6, 60%), and having a good quality of life (n=3, 30%). Individual participants (10%) described positive treatment experiences as receiving treatment close to home and from prominent HCPs or medical facilities (Table 2).
Table 2
Experience with MM Treatment
Concepts related to treatment experience
|
n*
|
%*
|
Patient Quote
|
Medication working/treatment response
|
8
|
80%
|
“Well, I guess the overarching most positive aspect of the treatment experience is so far it seems to be effective and seems to be keeping everything stable at this point.” – Male, 58 years
|
Side effects (pain, fatigue, diarrhea, nausea, hair falling out)
|
7
|
70%
|
“My pain is subsiding, …[my HCP is] able to help me control them… be able to control those side effects so that I can go about my day.” – Female, 53 years
|
Relationship with HCP
|
6
|
60%
|
“I would also add that I feel the communication with my physician is a huge positive to my experience. We dialogue about options. I’m never in a position where I’m told what to do as much as we consult about how treatment should progress and what options are available before we make any decisions.” – Female, 55 years
|
Treatment time burden (including travel time)
|
5
|
50%
|
“Other than having to come in often on some of the twice a week sometimes is an inconvenience. It’s down to just once a month now so that’s a good thing. The number of times you have to go in for treatment is a concern.” – Male, 71 years
|
Quality of life
|
3
|
30%
|
“Most important factors, I mean in perfect environment it would be something that would respond well to the myeloma. It would be something that could either be done at home or not as frequent. Maybe biweekly or monthly would be optimal and something that would allow us to have a quality of life so that we can be around others, we can be with our family members. We can really just live our life while we’re going through the treatment.” – Female, 47 years
|
Disease progression
|
3
|
30%
|
“Well, after my stem cell transplant became ineffective and I went into relapse it was then a question as to what would be the course of action to take next. Obviously having something to take was important to me to get back into remission or as close to remission as possible.” – Male, 71 years
|
Convenient location of treatment site
|
1
|
10%
|
“…my hospital is close to my office so I can keep my schedule when I go in for treatment. They’re very flexible, …so I would--I would say for the most part… it’s been positive.” – Male, 48 years
|
Prominent hospital
|
1
|
10%
|
“I love my doctor…the nurses, the staff generally care. It’s a very prominent hospital…their teams are some of the best --in the country and I--I trust them with patient welfare.” – Male, 48 years
|
* Number and percent of participants who endorse a concept
Participants commented on how a few RRMM treatment experiences can have both positive and negative aspects. Participants reported negative experiences from not seeing a treatment response (n=8, 80%), experiencing side effects (n=7, 70%), or experiencing disease progression (n=3, 30%). Participants also viewed the time burden of treatment, including travel time (n=5, 50%), as a negative experience.
Satisfaction with Treatment
When asked about treatment satisfaction, participants defined this as whether the RRMM treatment is a repeated positive or negative experience (Table 3). Reasons for participants’ RRMM treatment satisfaction included the medication working/treatment response (n=9, 90%), relationship with HCP (n=4, 40%), disease remission (n=2, 20%), maintaining quality of life (n=2, 20%), and getting treatment at a prominent hospital (n=1, 10%). Reasons for dissatisfaction with RRMM treatment included disease progression (n=5, 50%), side effects (n=4, 40%), treatment time burden (n=3, 30%), and treatment cost (n=1, 10%).
Table 3
Satisfaction/Dissatisfaction with MM Treatment
Concepts related to meaning of satisfaction
|
n*
|
%
|
Patient quote
|
Satisfaction with Treatment
|
|
|
|
Medication Working/Treatment Response
|
9
|
90%
|
“Well, I mean the ultimate satisfaction would be the effectiveness of the treatment, it’s working, is it working, is it not working? So far, my treatment seems to be working pretty well so therefore that is the ultimate satisfaction. That is why I’m doing this. That is why I’m disrupting my life and keeping this going on.” – Male, 58 years
|
Relationship with HCP
|
4
|
40%
|
“I’m satisfied knowing that I have one of the top doctors in the country treating me.” – Male, 57 years
|
Disease Remission
|
2
|
20%
|
“Obviously having something to take was important to me to get back into remission or as close to remission as possible.” – Male, 71 years
|
Maintaining Quality of Life
|
2
|
20%
|
“I think it’s…the ability to conduct myself at the highest level on a regular basis, so quality of life. Can I get up this morning and do what I need to do, eat fairly routine normal food, sleep well.” – Female, 55 years
|
Prominent Hospital
|
1
|
10%
|
“Oftentimes the negative has been the frequency of my treatment. My specialist is about 140 miles away and so when I’m there twice a week it’s a lot. Sometimes we are there for treatment twice a week, sometimes we’re there for simple blood work and other treatments. When I’m hospitalized I go to that hospital as well which is over by my specialist. Everything for me is out of town but that’s by choice. I mean that’s where I prefer to get my treatment.” – Female, 47 years
|
Dissatisfaction with Treatment
|
|
|
|
Disease Progression
|
5
|
50%
|
“Well for me personally, at this point, um, I’m not satisfied because I have not hit remission at any point… the best I’ve gotten is…very good response, um, so it’s been very, very tough for me. I would say I’m dissatisfied…with my experience because the disease is just so--it seems to be so strong…every therapy that we’ve tried…I’ve relapsed.” – Female, 53 years
|
Side Effects
|
4
|
40%
|
“You’re dissatisfied if…you get some side effects that are unbearable or are such that even with the satisfactory number situation that you feel like it’s not tolerable.” – Male, 71 years
|
Treatment Time Burden
|
3
|
30%
|
“The treatments I receive are four or five hours at a time. That’s a full day shot. If you’re doing that twice a week it’d be very hard to maintain a job.” – Male, 71 years
|
Treatment Cost
|
1
|
10%
|
“One thing to me that I would again put under the dissatisfying category, would be sometimes the cost. Lord it’s expensive to have myeloma. I think we all know that. I have pretty good insurance but there I still a lot of out of pocket cost and that’s a little dissatisfying certainly, but it’s part of the treatment.” – Male, 58 years
|
*n: Number of participants who endorse a concept
|
Cognitive Interview Results
The SEQ-MM v0.1 and v0.2 were reviewed in two rounds. Across the rounds, it took participants approximately five minutes to complete the questionnaire. Patient feedback from the cognitive interview portion of the focus group resulted in revisions to the measure.
Participants described the questionnaire and instructions as “simple,” “easy to understand,” “straightforward,” and “decent.” Participants spontaneously commented that using a five-point VRS works well for the questionnaire. Based on patient feedback, the response options of some items were also revised, as about 70% of patients preferred the five-point VRS over the three-point scale or 11-point numeric rating scale (NRS); they indicated their preference for a consistent scale throughout the questionnaire. All participants were clear on the item recall periods and understood the phrase “most recent.” After the second round, the SEQ-MM v0.2 was revised to include 15 items capturing the item “time spent receiving treatment.” Additional file 5 provides the item history, summarizing revisions made to the newly-developed SEQ-MM v1.0.
Revised CF
The CF for the SEQ-MM v1.0, linking the individual items to the hypothesized domains, was revised based on focus group feedback (Figure 3). The final SEQ-MM v1.0 includes 15 items (Additional file 6). Twelve items capture treatment experience: treatment burden (five items), time burden (five items), and travel burden (two items). Additional single items include: treatment compliance (one item), general health (one item), and an overall satisfaction item (one item).
Other Questionnaire Results
Satisfaction with Care
The majority of participants (90%) rated their cancer care team as seven or higher on an 11-point NRS (worst to best cancer care team). Most participants (70%) felt they received benefit from the treatment, with a few side effects (60%), many side effects (20%), or no side effects (20%). All participants stated that they were able to tolerate the treatment despite the side effects. All participants reported that their cancer care team clearly explained their treatment in person (90%), or in addition, provided written materials (30%).
Time Burden
The majority (70%) reported that office/clinic visits were scheduled at times that were convenient for them; 30% said that times were sometimes convenient for them. On average, patients spent 174 minutes (126 SD; range 66 to 360) in the clinic to receive treatment. Participants reported taking about 48 minutes (66 SD; range 18 to 240) to travel one way to receive treatment, with 80% of patients traveling one to three times per month. Most participants (80%) reported driving themselves to treatment, and 60% were accompanied by another person.
Indirect Costs
Participants reported paying for gas (80%), parking (30%), or taxi fare to the clinic (30%). One participant (10%) reported needing to find temporary lodging to receive treatment. On average, patients paid $16.50 ($15.50 SD; range $1 to $50) for gas, $10 ($5.00 SD; range $5 to $15) for taxi fare, $16.50 ($19.10 SD; range $3 to $30) for parking, and $200 for lodging. Four participants (40%) reported that insurance covered all costs, and six participants (60%) reported out-of-pocket treatment costs ranging from $50 to $6,000 with a mean of $1,764.20 ($2,351 SD).