Background
Migraine is one of the most common disabling diseases in the world,1 but also remains underdiagnosed and undertreated. 2–4 Recent advancements in migraine therapy contribute to a growing variety of available treatments and to variations in treatment benefits. Acute therapies focus on the rapid alleviation of symptoms once a migraine attack begins, while preventive treatments aim to reduce the overall frequency, duration, severity, and impact of migraine attacks.5,6 Treatment aims have evolved through decades of clinical investigation driven by the characteristic features of migraine attacks (e.g., moderate-severe pain, nausea, photophobia, and phonophobia) and episodic or chronic occurrence. Although studies in the field of migraine often reference patient priorities or preferences for treatment,7–11 published, systematic qualitative evaluation of treatment priorities directly by people living with migraine is limited. Prior studies that used qualitative methodology specifically to assess treatment priorities included a mix of stakeholders and found significant prioritization differences between people with migraine and other stakeholders.12,13 Similarly, systematic reviews have been conducted to document the wide variety of outcomes that have been measured in migraine research, but these may or may not accurately reflect the treatment priorities of people living with migraine.14–17 These reviews demonstrate that publications are inconsistent in reporting whether and how people with migraine have contributed to the selection and definition of these outcomes. Even when such information is summarized, it does not address whether patient participants engaged in any systematic prioritization of the relative importance of different outcomes or benefits of treatment.
The Migraine Clinical Outcome Assessment System (MiCOAS) project is a multi-stage project funded by the U.S. Food and Drug Administration (FDA) to develop a patient-centered core set of outcomes and endpoints for use in migraine clinical trials. As part of the project, the MiCOAS research team has gathered data from people living with migraine through qualitative interviews that explored experiences with migraine symptoms and burdens and inquired about perspectives on treatment through a ranking exercise.
Objective
To address the gap in understanding regarding the treatment priorities of people with migraine, the MiCOAS team conducted qualitative interviews that included a structured exercise in which participants were asked to rank-order two pre-defined lists of potential treatment benefits or outcomes, one for acute treatments (8 benefits) and one for preventive treatments (11 benefits). Participants were asked to explain their rationale for each ranking and to describe any additional benefits they perceived that were not included in the pre-defined lists. This is a primary analysis of the data from the interviews.
Methods
Participants with self-reported, medically diagnosed migraine were recruited through study announcements distributed by the Coalition for Headache and Migraine Patients (CHAMP, https://headachemigraine.org/) via newsletters and social media channels. CHAMP is a coalition of patient advocacy organizations focused on migraine and headache. CHAMP was selected because of its capacity to reach a large, diverse audience of people with migraine, as well as caregivers and clinicians who might share the announcement. Broad outreach also afforded an efficient way to reach people who have typically been underrepresented in migraine research, such as males and racial or ethnic minorities, while still permitting the selection of an overall sample that was representative of clinical trial participants and people who seek primary or specialty medical care for migraine.
The study announcement directed people to a dedicated study website that described the study and included a link to an electronic eligibility screening questionnaire. Participants who met the eligibility criteria were directed to an electronic informed consent form and those who e-signed the consent form were then directed to complete a health and demographic questionnaire.
Eligible participants were current US residents self-reporting a medical diagnosis of migraine and screened positive for migraine on the ID-migraine screener (endorsing two or more of the following: disability due to headache ≥1 day in the past three months, phonophobia, or nausea with headache),18 were able to complete an interview in English, aged 18–75, and were willing to participate in a 90-minute recorded interview. Exclusion criteria included 1) self-report of a medical diagnosis of multiple sclerosis, schizophrenia, bipolar disorder, cognitive impairment, Alzheimer’s disease or dementia, or epilepsy, 2) screening positive for alcohol or drug abuse over the past 3 months using the CAGE questionnaire,19 or 3) self-reported diagnosis, symptoms or hospitalization related to COVID-19 infection. The study took place July-September 2020.
From the pool of 428 eligible individuals, 40 participants were selected using iterative purposive sampling aimed at achieving a balanced representation of episodic and chronic migraine (EM and CM, respectively) using enrollment targets for headache frequency (see Table 1). These targets were intended to ensure the inclusion of people with EM who experience different numbers of headaches and limit the inclusion of people with very low or very high frequency headaches who would be excluded in many clinical trials. In addition, sampling aimed to achieve a diverse representation of demographic characteristics such as sex, race, ethnicity, education, employment status, income, and use of acute and preventive treatments. Participants were enrolled in 8 waves of 4–6 interviews each and the demographic characteristics of the sample of completed interviews was used to determine priority characteristics for the next wave. Interview results were also monitored for the achievement of data saturation.20
Table 1.
Targeted Sampling by Headache Frequency
| Headache Frequency | Enrollment Target |
|---|---|
| 0–1 headache day a month | n=2 |
| 2–3 headache days a month | n=6 |
| 4–7 headache days a month | n=6 |
| 8–14 headache days a month | n=6 |
| 15–23 headache days a month | n=18 |
| 24 or more headache days a month | n=2 |
| TOTAL | N=40 |
Interviews focused primarily on topics related to migraine symptoms and impacts. During the last 15–25 minutes of the interview, a structured visual rank ordering exercise of acute and preventive treatment benefits was conducted. The interview guide, developed by the investigators, was piloted in the field with two volunteer participants prior to data collection. All interviewers were trained on the protocol and observed by senior members of the research team (MTG, KM). Interviews were conducted in 2020 via web-conferencing. Interviews were recorded with participant consent and transcribed verbatim for use in analysis (identifying details were redacted from transcripts).
For the rank ordering exercise, the interviewer displayed a pre-specified list of acute and preventive pharmacologic treatment benefits using QuestionPRO and the Microsoft Teams screen-sharing function. Participants were asked to rank the items in order of importance while providing a verbal explanation of their rankings. The interviewer re-ordered items on the screen to match the participant’s statements. Interviewers also asked probing questions about why participants ordered items as they did and inquired about any missing priorities that the participant believed should be included. Participants were not required to rank all items on the list but could choose items to rank and disregard the remainder.
The lists of treatment benefits (Figure 1) were developed through an iterative process that included consideration of four systematic reviews of migraine or headache endpoints and outcomes,14–17 discussions with the MiCOAS study’s External Technical Advisory Committee (ETAC), and feedback from the FDA. The ETAC included physicians who specialize in migraine, researchers, pharmaceutical industry representatives, and one patient advocate living with migraine. Iterative discussions focused on articulating treatment benefits in plain language and developing suitable definitions. Some benefits appeared on both lists and were labeled and defined in the same way, with the exception of the benefit of improved emotional well-being. For acute treatment, this benefit was labeled as “improved feelings of well-being” as a way to reflect the immediate mood benefits that may arise when an acute treatment relieves a migraine attack. For preventive treatment, this benefit was labeled as “improved emotional health” to reflect the broader, longer-term emotional benefits that successful preventive treatment may bring about in people’s lives, including between attacks.
Figure 1.
Benefits of acute and preventive treatments provided to interview participants for ranking exercise
Ethics Review
This study was reviewed and approved by the WCG Institutional Review Board.
Analyses
Interview data were analyzed by computing mean, standard deviation (SD), median, interquartile range (IQR), mode, and range of ranks; examining the number of participants selecting each rank for each benefit; and conducting content analysis to assess patterns and themes in participants’ rationale for ranking. Content analysis was also conducted using Atlas.ti v. 8.0 software to assess themes in participant responses regarding perceived additional benefits that were important.
Results
Participant characteristics.
Table 2 provides a summary of self-reported participant demographic and clinical characteristics. Participants ranged from 21–70 years of age (mean=44). The sample was 78% (n=31) female, 68% (n=27) White, and 23% (n=9) Black or African American. Just over half (47%, n=19) of the study sample reported having received a college degree. The sample was composed of both currently employed (55%, n=22) and unemployed (45%, n=18) individuals. Most of the sample (70%, n=28) reported an annual household income of <$100,000. Half of the participants (n=20) reported experiencing ≥15 headache days per month, and half (n=20) reported experiencing <15 headache days per month. All participants reported using acute treatment(s) and 88% (n=35) reported using preventive treatment to reduce the frequency or severity of migraine during the past year. Participants selected from extensive lists of therapies that included prescription medications, over-the-counter treatments, and vitamin supplements, as well as an ‘Other, please specify’ option. Nine participants (22%) reported using non-prescription preventive treatments such as magnesium or riboflavin.
Table 2.
Demographic, Headache and Treatment Characteristics of the Study Sample
| Variable | Category | Total Interview Sample (N=40) |
|---|---|---|
| Age, n (%) | 18–24 years old | 5 (12) |
| 25–44 years old | 17 (43) | |
| 45–64 years old | 13 (33) | |
| 65 years and older | 5 (12) | |
| Gender, n (%) | Women | 31 (77) |
| Men | 7 (18) | |
| Genderqueer/ gender non-binary, transgender person | 2 (5) | |
| Race*, n (%) | White | 27 (67) |
| Black or African American | 9 (23) | |
| American Indian or Alaskan Native | 4 (10) | |
| Asian | 3 (7) | |
| Native Hawaiian or Other Pacific Islander | 1 (2) | |
| Other** | 1 (2) | |
| Prefer not to answer | 1 (2) | |
| Ethnicity/race*, n (%) | Hispanic | 9 (23) |
| Non-Hispanic | 31 (77) | |
| Relationship Status, n (%) | Married or partnered | 19 (48) |
| Not married or partnered | 21 (52) | |
| # of Other Adults in Household, n (%) | None | 8 (20) |
| 1–2 | 27 (68) | |
| 3–4 | 5 (12) | |
| Children in Household, n (%) | None | 26 (65) |
| 1 | 5 (12) | |
| 2 or more | 9 (23) | |
| Education, n (%) | Grade 12 or GED equivalent | 3 (8) |
| Associates degree, technical school, or trade apprenticeship; Some college (No degree awarded) | 18 (45) | |
| College Degree or Advance degree | 19 (47) | |
| Employment*, n (%) | Paid employment | 22 (55) |
| Student | 8 (20) | |
| Homemaker | 3 (8) | |
| Retired | 6 (15) | |
| Unemployed | 2 (5) | |
| Disabled (disability or leave of absence for any reason) | 10 (25) | |
| Other | 1 (2) | |
| Household Income, n (%) | Under $22,000 | 8 (20) |
| $22,000 to $49,999 | 10 (25) | |
| $50,000 to $99,999 | 10 (25) | |
| $100,000 and over | 8 (20) | |
| Prefer not to answer | 4 (10) | |
| Migraine Subtype by Frequency, n (%) | <15 headache days per month on average (Episodic Migraine***) | 20 (50) |
| ≥15 headache days per month on average (Chronic Migraine***) | 20 (50) | |
| Migraine with aura | 14 (35) | |
| Migraine without aura | 26 (65) | |
| Average Number of Headache Days per Month, n (%) | 0–1 | 0 |
| 2–3 | 6 (15) | |
| 4–7 | 8 (20) | |
| 8–14 | 6 (15) | |
| 15–23 | 18 (45) | |
| 24 or more | 2 (5) | |
| Use of OTC or Prescription Acute Pharmacologic Treatment (within past year), n (%) | Yes | 40 (100) |
| Use of OTC or Prescription Preventive Pharmacologic Treatment, n (%) | Yes | 35 (87) |
Total percent exceeds 100 because participants were able to select more than one race and/or employment status category
Respondent reported races of “White, South American, and North African” and chose the label “other”
Chronic migraine was defined as an average monthly headache day frequency of ≥15 per month among people who meet criteria for migraine as per Silberstein-Lipton criteria and episodic migraine was the complement. It was not possible to assess the ICHD-3 criteria.
Benefit ranking results.
Mean, median, mode, and range of ranks for each treatment benefit provided by participants are shown in Table 3. All participants completed the ranking exercise so there were no missing data. Most participants provided a ranking for all benefits on both lists. Three participants did not rank all items on both lists. One participant did not rank all acute treatment benefits and another did not rank all preventive benefits. Removing these participants from analysis would have made small numeric differences in mean values, but would not have altered the overall order of mean, median, or mode rankings. Notably, the range of rankings shows that every treatment benefit was ranked at or near the bottom by at least one participant, as well as at or near the top by at least one person. Only three treatment benefits were ranked by all 40 participants: greater ability to participate in usual daily activities, fewer attacks, and less severe intense pain.
Table 3.
Results of ranking of potential benefits by participants
| Mean (SD) | Median (IQR) | Mode | Range | |
|---|---|---|---|---|
| Acute treatment benefits | ||||
| Pain relief | 2.2 (1.6) | 2 (2) | 1 | 0–8 |
| Relief of other symptoms | 4.0 (2.1) | 4 (3) | 4 | 0–8 |
| Absence of pain | 3.1 (2.7) | 2 (4) | 1 | 0–9 |
| Absence of other symptoms | 4.1 (2.3) | 3.5 (3.2) | 3 | 0–9 |
| Greater ability to participate in your usual daily activities | 5.0 (2.3) | 5 (4) | 3 | 1–9 |
| Greater ability to do physical things | 6.4 (2.5) | 7 (3.2) | 8 | 0–9 |
| Less “brain fog” | 5.5 (2.2) | 5.5 (3) | 5 | 0–9 |
| Improved feelings of well-being | 6.1 (2.3) | 6 (3) | 6 | 0–9 |
| Less need for other medications or treatments | 6.4 (2.4) | 7 (4) | 9 | 0–9 |
| Preventive treatment benefits | ||||
| Fewer days with migraine each month | 2.3 (1.7) | 2 (2) | 1 | 0–10 |
| Fewer migraine attacks each month | 2.7 (1.8) | 2 (2.2) | 2 | 1–9 |
| Longer periods of time in-between your migraine attacks | 4.6 (2.2) | 4.5 (3) | 3 | 0–10 |
| More predictability | 7.5 (3.3) | 8 (4.2) | 11 | 1–11 |
| Less severe/intense pain when a migraine attack happens | 3.8 (2.1) | 3.5 (3) | 4 | 0–9 |
| Shorter attacks when they happen | 5.1 (1.9) | 5 (2) | 4 | 0–9 |
| Less severe symptoms when a migraine attack happens | 5.2 (2.8) | 5 (3) | 5 | 0–11 |
| Greater ability to participate in usual daily activities | 7.2 (2.8) | 7.5 (3) | 7 | 0–11 |
| Less “brain fog” | 7.9 (3.1) | 9 (3) | 10 | 0–11 |
| Improved emotional health | 7.8 (3.4) | 9 (4) | 11 | 0–11 |
| Less need for acute migraine medications | 7.5 (3.5) | 9 (4.5) | 11 | 0–11 |
A rank of 1 indicates the benefit was a top priority; a rank of 0 indicates that the participant did not rank the outcome
Acute treatment benefits
Interview participants consistently ranked pain relief or absence of pain as their number one priority for acute treatment benefit (Figure 2). These two options each received 17 number one rankings (Table 4), with 85% of participants selecting one of these options as their top priority. The mean ranking for pain relief was considerably higher than the mean ranking for absence of pain because a substantial number of participants (n=11) ranked pain relief second and few participants (n=4) ranked it lower than 4th place. Rankings for absence of pain were more dispersed, with 12 participants selecting a ranking lower than 4th place.
FIGURE 2.
Average (mean) priority rankings for acute treatment benefits reported by interview participants (N = 40) during virtual ranking exercise (lower value = higher ranking).
Table 4.
Number of participants selecting each rank for each acute treatment benefit (n=40)
| Treatment Benefit | Rank | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| 0 | 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | |
| Pain relief | 1 | 17 | 11 | 3 | 4 | 3 | 0 | 0 | 1 | 0 |
| Relief of other symptoms | 3 | 1 | 7 | 5 | 10 | 5 | 3 | 3 | 3 | 0 |
| Absence of pain | 1 | 17 | 6 | 3 | 1 | 3 | 2 | 3 | 2 | 2 |
| Absence of other symptoms | 2 | 1 | 8 | 9 | 6 | 4 | 2 | 3 | 4 | 1 |
| Greater ability to participate | 0 | 2 | 2 | 12 | 3 | 2 | 8 | 5 | 2 | 4 |
| Greater ability to do physical things | 2 | 0 | 1 | 2 | 5 | 3 | 4 | 5 | 10 | 8 |
| Less “brain fog” | 2 | 0 | 2 | 3 | 4 | 9 | 7 | 7 | 1 | 5 |
| Improved feelings of well-being | 1 | 2 | 0 | 3 | 2 | 5 | 8 | 7 | 7 | 5 |
| Less need for other medications or treatments | 1 | 0 | 3 | 0 | 5 | 5 | 4 | 5 | 6 | 11 |
Gray shading indicates the mode; A rank of 1 indicates the benefit was the top priority; A rank of 0 indicates that the participant did not rank the item
As shown in Figure 2, average rankings for relief or absence of other migraine symptoms were similar and these were high priorities for many participants. Benefits related to functioning were ranked on average as the next highest priorities, while less need for other treatments was ranked last. These mean rankings generally aligned with the median and mode (Table 3), with the exception of “greater ability to participate in your usual daily activities.” This benefit was ranked 3rd by 12 participants compared with absence of other symptoms, which was ranked 3rd by nine participants.
Preventive treatment benefits
Figure 3 displays average rankings for benefits associated with preventive treatment. Interview participants prioritized reductions in migraine frequency, severity of symptoms, and the duration of attacks. Notably, 31 of the 40 participants (78%) selected fewer days, fewer attacks, and longer periods of time between attacks as their top three priorities (Table 5). Participants expressed that these benefits were interrelated: “Because you’re getting less migraines, so there’s going to be longer periods of time in between them. And you’re getting fewer [days] each month, and then fewer migraine attacks.” (00–14).
FIGURE 3.
Average (mean) priority rankings for preventive treatment benefits reported by interview participants (N = 40) during virtual ranking exercise (lower value = higher ranking).
Table 5.
Number of participants selecting each rank for each preventive treatment benefit (n=40)
| Treatment Benefit | Rank | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 0 | 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 | 11 | |
| Fewer days with migraine | 3 | 12 | 11 | 8 | 3 | 2 | 0 | 0 | 0 | 0 | 1 | 0 |
| Fewer migraine attacks | 0 | 11 | 13 | 6 | 5 | 2 | 1 | 1 | 0 | 1 | 0 | 0 |
| Longer periods of time between attacks | 1 | 2 | 3 | 8 | 6 | 7 | 5 | 4 | 2 | 1 | 1 | 0 |
| More predictability | 3 | 1 | 0 | 1 | 2 | 3 | 3 | 4 | 4 | 5 | 5 | 9 |
| Less severe/intense pain | 0 | 6 | 5 | 9 | 9 | 3 | 2 | 2 | 3 | 1 | 0 | 0 |
| Shorter attacks | 1 | 0 | 2 | 5 | 10 | 4 | 9 | 4 | 4 | 1 | 0 | 0 |
| Less severe symptoms | 4 | 3 | 3 | 0 | 2 | 9 | 7 | 5 | 1 | 4 | 1 | 1 |
| Greater ability to participate in usual daily activities | 3 | 0 | 1 | 0 | 1 | 4 | 2 | 9 | 7 | 4 | 6 | 3 |
| Less “brain fog” | 3 | 0 | 2 | 0 | 0 | 1 | 2 | 4 | 7 | 7 | 8 | 6 |
| Improved emotional health | 3 | 3 | 0 | 0 | 0 | 1 | 4 | 1 | 5 | 7 | 8 | 8 |
| Less need for acute migraine medications | 4 | 2 | 0 | 2 | 1 | 2 | 2 | 3 | 4 | 5 | 6 | 9 |
Gray shading indicates the mode; A rank of 1 indicates the benefit was the top priority; a rank of 0 indicates the participant did not rank the item
Difference in Priorities for episodic vs. chronic migraine
Overall, people with EM and people with CM gave similar average rankings for acute treatment benefits (Figure 4). By contrast, people with CM on average ranked “more predictability” much higher than people with EM and gave a much lower average ranking for “greater ability to participate” (Figure 5). Conceptually, these benefits are related because the unpredictability of migraine attacks contributes substantially to impairments of daily life. For people with CM, the frequency of these unpredictable attacks results in a broad array of burdens, which may explain its higher ranking for this group. Unpredictability manifests in several ways as well: participants noted that migraine attacks can be unpredictable in when and how often they occur, but also in terms of which symptoms are present, how severe they are, and how long they last. The somewhat higher average rankings amongst those with CM for benefits such as shorter attacks, longer interictal periods, and less severe symptoms may reflect a desire for treatment that results in greater amounts of functional time over the course of a month. Importantly, participants with CM often commented on the perceived tradeoffs of treatment and the ways this factored into their thinking. For example, one participant said, “The main thing would probably be decreasing frequency. I think that’s like the first. Second would be probably severity. Like if I can’t have like less migraines, I’d rather them not be as bad. Those are like the two main things.” (00–29).
FIGURE 4.
Comparison of average priority rankings for acute treatment benefits reported by participants with episodic (n = 20) and chronic (n = 20) migraine.
FIGURE 5.
Comparison of average priority rankings for preventive treatment benefits reported by participants with episodic (n = 20) and chronic (n = 20) migraine.
Themes in Participant Ranking Rationales
A content analysis of participant comments during the ranking exercises demonstrated that several factors strongly influenced the ways that people prioritized benefits on each list. In all, 24 participants (60%) offered comments reflecting factors that influenced the way they ranked the outcomes provided.
Expectations about what treatment could achieve
About half of the participants (n=21) noted that their expectations about what medication could and could not do influenced their rankings. When participants believed that treatment could never achieve certain outcomes, they often ordered those benefits lower than their actual desire, including ranking them as lowest priorities. As one participant observed, “[less need for medication, greater ability to do physical things] those are the lowest priorities because I guess I’m always going to have a limitation to doing physical things. And I generally always needed some other form of medication or treatment. So 90% of the time, those things I have to do anyway, so I wouldn’t classify those are things that are important to me because, in 30 years or 40 years, there hasn’t been a drug that has effectively gone through this whole list and changed all those items for me” (00–04). For the acute treatment benefits, several participants noted that they selected a lower rank order for absence of pain because they did not believe it was a realistic outcome given their past experiences with treatment. One participant remarked, “I think because ultimately that [absence of pain] would be the goal. I guess that would probably be better off first. But I guess being realistic about it, sometimes that’s not always practical. Sometimes you don’t get just 100% pain relief. But at the same time, it would be ideally absence of pain would be the goal” (00–05). Another responded similarly, saying “I guess I expect relief more than I expect absence of – like I think absence, of course, is the goal but not likely to happen”(00–24). A third participant thought absence of pain “just feels again like magically hypothetical” (00–18).
Expectations about treatment side effects influenced some rankings. One participant ranked less brain fog as a low priority and noted “When you take something that messes with your CNS, you’re never going to get something that cures the pain that doesn’t create a side effect. I just don’t believe that’s ever going to happen” (00–04). By contrast, another participant ranked less brain fog second and explained “Because a lot of times, when you do any medication, a side effect is more brain focusing, or just a feeling of being drugged, and that’s not fun” (00–06).
Participants’ expectations and beliefs about relationships among outcomes also influenced their rankings. For example, some participants who chose absence of pain as the most important benefit noted that they felt it was foundational and encompassed all other outcomes. As one participant said, “[With an absence of pain], everything else will kind of take care of itself.”(00–41). Another participant mentioned, “If you ever have the pain, obviously absence of pain is the goal. So that’s why I would put that at number one. And then relief of other symptoms. The other symptoms go hand in hand with pain based upon the descriptions, nausea, vomiting, sensitivity. Absence of pain is going to help with that.” (00–14)
Perceived tradeoffs and hierarchies of treatment benefits
Many participants were not simply ranking in order of pure importance but creating hierarchies or pathways amongst benefits, which then could result in a lower ranking for an ultimately desired benefit or a higher ranking for a benefit seen as a necessity. Seven participants (18%) ranked outcomes lower, including ranking them as lowest priorities, when they believed that achieving another high-ranked benefit would result in achievement of these outcomes. One participant commented, for example, “Greater ability to participate in daily activities. Put that one last. Yeah, because you’re able to do – if you don’t have them, I mean, you know, the less migraine attacks you have, you’re going to be able to participate in everything. You’ll be able to do your day-to-day activities at home, your day-to-day – be able to exercise, you’re eating better, you’re eating healthier” (00–13). Four participants (10%) ranked less brain fog higher because cognitive function was important in their daily lives. One participant noted, for example, “I’m a software engineer, so I need to be able to think” (00–42). Another said, “If I’ve got brain fog, I’m not completely there, which would be the same reason to follow that with greater ability to participate in daily activities, because there’s no point in me being there if I’m not mentally there” (00–23).
The variability and unpredictability of migraine experiences made the exercise challenging for participants who wanted to consider layers of tradeoffs. For example, one participant mulled over how to order preventive treatment benefits to achieve better quality of life both during and between attacks: “I’m just trying to think of what would be the best case scenario, if – like if something were working to prevent them from happening as frequently, it seems like the less severe pain would be the best of those three and then longer periods of time in between would mean higher quality of life on those days and then if I did have it, then less severe symptoms would be better.” (00–08). Another participant 00–14 had difficulty deciding exactly how different acute benefits should be ordered to achieve the actual outcome they wanted, which was absence of pain and ability to get on with life, noting “I think they all interrelate. […] you can’t do daily activities without getting rid of the brain fog or the pain relief. So, you got to start with that and work your way through each one to get to the other.” Another participant put it very succinctly: “Dang. Like I said, all of these are like number one.” (00–16).
Additional potential treatment outcome priorities identified
Participants identified several other priorities related to benefits of treatment that were important to them. These included benefits such as limited side effects (53%, n=21 participants) and the reliability of the treatment’s effectiveness (55%, n=22). One participant commented on their experience with several treatments saying, “sometimes they worked and sometimes they didn’t, and then you feel like you can’t trust this drug and you’re playing Russian roulette every time…So if it’s not somewhat consistent, it’s worthless. For me, it has to be, like, at least 75% to 80% effective.” Participants also mentioned mode of administration (63%, n=25) and availability or affordability of medication (13%, n=5) as important factors when considering treatment tradeoffs. One participant noted, for example, “I wish there was ones that I could take more often […] like if I have really bad migraines all week, I cannot take this abortive medication every day or anything. I have to really limit it. So I guess it would be nice to have something that was more accommodative to that. The one thing that I do prefer about injections is that you don’t have to swallow water or whatever you have to drink to take the pill because, when I’m so nauseous like that, it’s very hard to swallow and drink.” (00–24)
Limitations
The way that “pain relief” and “absence of pain” were defined (see Figure 1) may not have matched the way many participants thought about these concepts based on the label phrases alone, and this may have influenced rankings. Pain relief was defined as a lessening of pain after a dose of acute treatment, while absence of pain was defined as pain freedom after treatment. Interview transcripts suggest that some participants interpreted ‘absence of pain’ as prevention of pain and ranked it lower because this outcome seemed less realistic.
The acute treatment benefits list was always offered first and benefits on both lists were always offered in the same order which may have resulted in some primacy bias.
Participants could offer comments on other benefits of treatment, but were not asked to rank them or to explain their relationship to the listed benefits. For example, although many people mentioned the reliability of treatment efficacy, the relationship between this benefit and other outcomes is unknown. This is of particular interest because the benefit of “more predictability” was included but not ranked highly by most participants, leaving an open question about how people with migraine think about the reliability of treatment efficacy relative to predictability in the number or length of attacks.
Finally, the size and composition of the sample was determined by the overall goals of the larger MiCOAS project. A larger or randomly-selected sample may have produced different results from this structured ranking exercise.
Conclusion
Understanding the ways patients view and prioritize potential treatment benefits is critically important to therapy development, clinical trial design, and clinical practice. The existing clinical emphasis in acute treatment on migraine symptom prevention and relief aligns with overall priorities expressed by the overwhelming majority of the MiCOAS qualitative interview study participants; however, it is important to acknowledge that these priorities were frequently ranked highly with the assumption that they would necessarily lead to other benefits on the list. If a treatment offered pain relief, but no other benefits, it seems fair to say that these participants might find that treatment fell short of their needs. Similarly, clinical priorities for preventive treatment related to overall reduction in migraine attacks aligned with priorities selected by most study participants. Importantly, however, participants with CM—the population most likely to use and benefit from preventive treatments—also prioritized predictability. This, in turn, aligned with the identified gap in the pre-defined list of potential benefits: reliability of treatment efficacy. Put simply, people living with migraine want treatments that work consistently and provide them with a greater sense of confidence that they can make plans and live their lives.
The ranking exercise results appear to support the conclusion that clinical trial research and drug development are focusing on outcomes that are prioritized by people living with migraine. However, in this study, the numeric results do not give a fully accurate picture of what truly matters to people using these treatments. Rather, the ranking exercises revealed complexities that intervened and influenced the rankings offered by most participants. These complexities included assumptions about how outcomes lead to one another, assumptions about what migraine therapies can or ever will be able to achieve, and individual assessments of the tradeoffs or pathways among benefits.
From the standpoint of clinical outcomes assessment, these findings underscore the importance of taking a broader view of how treatment efficacy should be evaluated. Participants in this study expressed strong assumptions that addressing pain and reducing the number of days with migraine symptoms will necessarily lead to broader improvements, such as improved ability to carry out daily activity that requires physical or cognitive functioning. Nevertheless, all the participants used prescription treatments with proven efficacy and all of them still reported substantial impairment of functioning. These impairments were related, at least in part, to the limitations of treatments that may not work every time, may cease to be effective over time, or may not deliver sufficient benefits quickly enough or for long enough. These features of migraine treatments could be assessed to develop a better understanding of the relationships between pain relief or attack prevention and the other outcomes that matter to patients. Similarly, consistent assessment of core functioning outcomes alongside measures of symptom severity and frequency could permit a better understanding of which symptoms must be relieved and to what degree to deliver improvements in function. Future migraine research would be improved by including these types of additional outcomes so that clinicians, scientists, regulatory agencies, and patients can better understand the benefits and drawbacks of available treatments.
Acknowledgements:
The authors would like to thank the US Food and Drug Administration including Robyn Bent, MS; the Coalition for Headache and Migraine Patients (CHAMP) for assisting in recruitment; and Alyssa A. Uzumcu, BA, Alexis Cooke, PhD, Nancy M. Touba, MPH, David W. Dodick, MD, Walter F. Stewart, PhD, MPH, Elizabeth Nicki Bush, MHS, Roger Cady, MD, Katie M. Golden, BA, Peter Goadsby, MD, PhD.
Statement of funding:
This manuscript was supported by the Food and Drug Administration (FDA) of the US Department of Health and Human Services (HHS) as part of a financial assistance award (UH3FD006795) totaling $1,599,834 with 100 percent funded by FDA/HHS. The contents are those of the authors and do not necessarily represent the official views of, nor an endorsement by, FDA/HHS or the US Government.
Abbreviations:
- CHAMP
Coalition for Headache and Migraine Patients
- CM
chronic migraine
- COVID-19
coronavirus disease 2019
- EM
episodic migraine
- FDA
Food and Drug Administration
- MiCOAS
Migraine Clinical Outcome Assessment System
- ETAC
external technical advisory committee
Footnotes
Conflict of interest statement: Rikki Mangrum is a full-time employee of Vector Psychometric Group, LLC, which in turn received funds from the FDA to conduct the research detailed in the manuscript. Maya T. Gerstein was a full-time employee of Pharmerit/OPEN Health, which in turn received funds from Vector Psychometric Group LLC and the FDA to conduct the research detailed in the manuscript. Calvin J. Hall, III, is a full-time employee of Vector Psychometric Group, LLC, which in turn received funds from the FDA to conduct the research detailed in the manuscript. Dawn C. Buse is a part-time employee of Vector Psychometric Group LLC, which in turn received funds from the FDA to conduct the research detailed in the manuscript. In addition, she receives research funding from the National Headache Foundation and Amgen. She has been a consultant to Allergan/Abbvie, Amgen, Lilly, Lundbeck, and Teva Pharmaceuticals. Carrie R. Houts is a full-time employee of Vector Psychometric Group LLC, which in turn received funds from the FDA to conduct the research detailed in the manuscript. James S. McGinley is a full-time employee of Vector Psychometric Group LLC, which in turn received funds from the FDA to conduct the research detailed in the manuscript. James S. McGinley has received honoraria/payment/reimbursement from the journal Cephalalgia (biostatistics editor). James S. McGinley has also received research grants/support from Amgen, Inc. and the National Headache Foundation. Kelly P. McCarrier is a full-time employee of Pharmerit/OPEN Health, which in turn received funds from Vector Psychometric Group LLC and the FDA to conduct the research detailed in the manuscript. Richard B. Lipton received research support from the FDA on the MiCOAS project. In addition, he receives research funding from the NIH, the National Headache Foundation, and the Marx Foundation. He also receives research support from Allergan/Abbvie, Amgen, Biohaven, Eli Lilly, and Electrocore. He receives personal fees as a consultant or advisor from Allergan/Abbvie, Amgen, Biohaven Holdings, Dr. Reddy’s, GSK, Grifols, Eli Lilly, Lundbeck, Merck, Novartis, and Teva Pharmaceuticals. He holds stock or options in Biohaven Holdings and CtrlM Health. In addition, he receives royalties for Wolff’s Headache, 7th and 8th editions. R. J. Wirth is a full-time employee of Vector Psychometric Group LLC, which in turn received funds from the FDA to conduct the research detailed in the manuscript.
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