Patient Preferences and Values in Decision Making for Migraines: A Systematic Literature Review

Objective To comprehensively summarize the evidence on the preferences and values of migraine patients. Methods We searched PubMed, Embase, Web of Science, China National Knowledge Infrastructure, Sino-Med, Chongqing VIP, and Wanfang Data for studies on the preferences and values of migraine patients. A qualitative review was performed, but no quantitative synthesis. Results Twenty‐one studies were finally included, involving a total of 8701 participants. Patients expected a cure, to be symptom-free, a reduction in frequency of headaches, a reduction in severity of headaches, and an improved quality of life from their preventive treatment. Patients expected rapid pain relief, complete pain relief, return to normal activities, no recurrence, and no adverse events from their acute symptomatic treatment. Conclusion Efficacy is the primary consideration in the treatment of migraine. Specifically, the most important embodiment of patient preferences and values is the reduced frequency of attacks with preventive treatment as well as prompt analgesia with acute symptomatic treatment.


Introduction
Patient preferences and values are mostly convergent with those of healthcare workers, but there are also differences [1]. As direct recipients in the process of disease diagnosis and treatment, the preferences and values of patients cannot be ignored [2]. Patients themselves have expressed interest in the decision-making process, and their adherence to treatment can be simultaneously improved when they participate in the decision-making process [3,4]. Evidence-based medicine states that optimal clinical decisions should take into account the experience of clinicians, clinical research evidence, and patient preferences and values [5]. Furthermore, evidence of patient preferences and values has also been emphasized in the development of guidelines [6][7][8][9][10].
Migraine is the third most prevalent disorder and the first cause of disability [11]. Current mainstay of migraine treatment is drugs, including prophylactic and analgesic drugs [12]. e use of prophylactic drugs aims to lessen the frequency and severity of the migraine attacks, and the common prophylactic drugs include antihypertensives (e.g., β-blockers, calcium channel blockers, and angiotensinconverting enzyme inhibitors), antidepressants, anticonvulsants, and antihistamines [12]. e use of analgesic drugs aims to prevent a migraine attack or to stop it once it starts, and the common analgesic drugs include triptans, nonsteroidal anti-inflammatory drugs, acetaminophen, combination (acetaminophen, caffeine, and aspirin), and narcotics [13]. Other treatments such as application of pressure, cold, or heat, acupuncture, and surgical treatment have also gradually attracted attention in recent years, but evidence support is still lacking [14].
According to the Grading of Recommendations, Assessment, Development, and Evaluation approach, patient preferences and values refer to the relative importance of the patient for the outcome or health state of interest [9]. Based on the experience of guideline experts [10], we defined patient preferences and values as the perspectives, expectations, and goals of patients regarding treatment attributes. Treatment attributes were divided into treatment process attributes and outcome attributes. Among them, treatment process attributes included treatment strategy, duration, route of administration, formulation, and cost; treatment outcome attributes included treatment benefits and side effects [10].
ere had been a significant increase in the number of studies investigating the preferences and values in patients with migraines; to comprehensively summarize the evidence, we carried out this systematic literature study.

Eligibility Criteria.
Inclusion criteria were as follows: studies related to patient preferences and values for migraine therapy, both the preventive treatment and the acute symptomatic treatment; studies that examined the context of the consideration of migraine therapy and how patients value alternative health states and experiences with treatment; and studies that examined the choices patients make when presented with decisional aids for management options regarding migraine therapy. e exclusion criteria were reviews, letters, posters, case reports, and case series.

Study Selection and Data Extraction.
Two investigators independently read titles, abstracts, and full text to identify eligible studies. Any conflicts were adjudicated through discussion. According to the characteristics of the included studies, we extracted the following basic information using a standardized data extraction form: the first author, year of publication, date of study conduction, type of study, number of patients, and their demographics (mean age, gender), treatment protocol, methods used for evaluating patient preferences and values, outcomes assessed, main results, and methodological characteristics.

Quality
Assessment. An evaluation of the quality of the included studies was performed with the instrument recommended by the Agency for Healthcare Research and Quality (AHRQ) [15]. ere were 11 items in the AHRQ checklist, and each item was evaluated using three evaluation options, yes (scored "1"), unclear (scored "0"), or no (scored "0"). e quality was classified into three levels: low quality � 0-3; moderate quality � 4-7; high quality � 8-11 [16].

Statistical Analysis.
A qualitative review was performed, but no quantitative synthesis. e results are presented in tabular form.

Results of Included Studies.
A total of 3774 articles were acquired from the electronic search, and 405 duplicates were excluded. After screening the titles and abstracts, 3259 articles were excluded. Afterwards, the full texts of the remaining 110 articles were read for further evaluation, and 89 articles were excluded. Finally, a total of 21 studies  were ultimately included. e selection process is shown in Figure 1.
Characteristics of the studies, including date of study conduction, country, study design, simple size, migraine status, treatments, methods of stated-preference assessment, and methodological quality of the studies, are shown in Table 2. e most commonly used methods for evaluating patient preferences and values are described briefly in Table 3.

e Preventive Treatment for Migraine.
Preferences and values for preventive treatment were reported in seven studies [17][18][19][20][21][22][23]. In general, all patients attached great importance to the preventive treatment of migraine. For treatment process, therapies with higher response rates, fewer adverse events, less frequent dosing regimens, and higher convenience were preferred [17,18,20,22]. For treatment outcome, patients expected a cure, to be symptom-free, a reduction in frequency of headaches, a reduction in severity of headaches, and an improved quality of life from their treatment [18,20,21]. Efficacy was the most important aspect of outcome in preventive treatment; some patients even did not mind taking more than one preventive agent at one time if greater efficacy could be achieved [22]. e preventive treatment for migraine was important; however, not all patients actually used this treatment [19]. More details are shown in Table 4.

Discussion
A literature search yielded several published studies on preferences and values among patients with migraines. In this research, we systematically evaluated studies reporting the preferences and values of patients with migraines, thus providing summarized evidence for clinicians.

Summary of Main Findings.
In this review, 21 studies enrolled 8701 participants were final included. In summary, evidence from these included studies suggested that the efficacy was the primary consideration in the treatment of migraine. For preventive treatment, therapies with higher response rates, fewer adverse events, less frequent dosing regimens, and higher convenience were preferred. Patients expected a cure, to be symptom-free, a reduction in frequency of headaches, a reduction in severity of headaches, and an improved quality of life from their preventive treatment. For acute symptomatic treatment, therapies with a faster onset of action, a longer duration of the effects, fewer adverse events, and lower price were preferred. Patients expected rapid pain relief, complete pain relief, return to normal activities, no recurrence, and no adverse events from their acute symptomatic treatment. Moreover, triptans were

Regimens for Migraines.
Preventive treatment for migraines should be preemptive, short term, or maintained. Antiepileptic drugs, β-blockers, antidepressants, calcium channel antagonists, botulinum neurotoxins, and serotonin antagonists are the most commonly used drugs for migraine prevention [12]. On the basis of evidence-based medical evidence, the first-line medications identified as effective include topiramate, divalproex, propranolol, metoprolol, and timolol; the second-line medications identified as effective include venlafaxine, amitriptyline, nadolol, and atenolol [38]. For migraine prevention, β-blockers are the most widely used drugs, which can reduce the frequency of attacks by more than 50%, and there are no absolute or relative contraindications [39]. Tricyclic antidepressants are also used to prevent migraines; however, only amitriptyline has proven efficacy in migraine. In addition, the high incidence of adverse events limits its use [40]. Since the efficacy of placebo-controlled trials has been confirmed, antiepileptic drugs are increasingly recommended for migraine. However, it is worth noting that most antiepileptic drugs may substantially interfere with the efficacy of oral contraceptives [41]. Furthermore, other medications such as calcium channel blockers, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, onabotulinumtoxinA, and complementary and alternative medicines cannot be recommended for migraine prevention due to the limited evidence quality [38]. For acute symptomatic treatment, the first-line medications for mild to moderate migraine are acetaminophen and nonsteroidal anti-inflammatory drugs, whereas triptans for moderate to severe migraines; for those with refractory migraine, dihydroergotamine and antiemetics are recommended for use as second-or third-line medications [42].

Ranking
Researchers ask patients to rate a set of outcomes on an ordered ''Likert-type" scale (rating) or to rank them from the most to the least important. Rating can also use visual analog scale and in this case utilities can be derived From Ref. [17]: ''patients were ranked on a seven-point scale, with 1 being "not at all likely" and 7 being "extremely likely," their likelihood of acceptance of and adherence to the new medication in scenarios in which either monthly or quarterly dosing is available" Researchers ask patients to choose between the health states as described in a clinical scenario during X years and a shorter life in normal health. e duration X is varied until the patient is unable to choose between the two options From Ref. [30]: ''three attacks were treated on each study medication. Assessment of subjective preference was evaluated, after which patients freely choose which study medication they wished to use to treat each of the three additional migraine attacks"

Standard gamble
Researchers ask patients to choose between two possible outcomes: a suboptimal health state that is certain and a gamble with one better (for example, full health) and one worse (for example, death or side effects) outcome possible. e probability of the gamble is varied during the experiment and the point of indifference is used to derive the utility of the health state From Ref. [18]: ''respondents valued a change from a 10% reduction in headache days per month to a 50% reduction more highly than avoiding the worst levels of adverse events. Nevertheless, respondents were willing to forgo some improvements in efficacy for less-severe adverse events" Patients tended to inject monthly or daily rather than twice a month when treating It was more important to change the number of migraine attack days from a 10% reduction to a 50% reduction than to avoid adverse events Kol et al. [19] Fifty-five percent of patients wanted to use prophylaxis; only 8% actually used this treatment Peres et al. [20] erapies with higher response rates, fewer adverse events, and less frequent dosing regimens were preferred Patients rated efficacy as the most important aspect of preventive treatment outcome Kelman [21] A percentage of 95.2 expected a reduction in frequency of headaches from their treatment, 95.6% a reduction in severity of pain, 79.7% to be symptom-free, 27.8% a cure, and 95.5% an improved quality of life Rozen [22] If greater efficacy could be achieved, patients did not mind using more than 1 prophylactic agent Wenzel et al. [23] e vast majority of patients wanted to use over-the-counter drugs to effectively prevent migraine 6 Pain Research and Management e use of acetaminophen and nonsteroidal anti-inflammatory drugs for mild to moderate migraine attacks is supported by strong evidence [42]. Moreover, nonsteroidal anti-inflammatory drugs have better efficacy than acetaminophen, but can cause gastric irritation or antiplatelet effects [43]. Triptans share a common mechanism of action and have strong evidence of effectiveness for moderate to severe migraine attacks [43]. However, different types of triptans have different routes of administration and kinetics, and they may be expensive [44]. Hence, appropriate individualized use is essential. Furthermore, other medications such as dihydroergotamine, opioids, and antiemetics have good evidence of effectiveness for migraine. However, they are reserved as second-line drugs due to adverse effects, abuse potential, route of administration, or cost [42].

Limitations.
To the best of our knowledge, this is the first study to summary the evidence on the preferences and values of migraine patients. However, limitations should be acknowledged. First, the definition and eligibility criteria for preferences and values are broad; the lack of standardized methods for reporting and identifying the evidence of patient preferences places additional limitations on our research. Second, it is tentative and empirical to use a systematic literature review method to summary evidence; there might be nonrigorous and inconsistent phenomena.

Conclusions
In summary, evidence from these included studies suggests that the efficacy is the primary consideration in the treatment of migraine. Specifically, the most important embodiment of patient preferences and values is the reduced frequency of attacks with preventive treatment as well as prompt analgesia with acute symptomatic treatment.

Data Availability
All data generated or analyzed during this study are included in this published article. In terms of dosage form, the order of priority was tablets, nasal spray, and subcutaneous injection Eighty-seven percent of patients had expected complete pain relief after treatment, 86% had no recurrence, and 83% had rapid pain relief Adelman et al. [25] Among the included patients, 188 chose orally disintegrating tablets, while 179 preferred conventional tablets Pascual et al. [26] e reasons for patient preference for either of the two triptans were faster onset, duration of action, fewer adverse events, and lower price Weidmann et al. [27] In terms of dosage form, the order of priority was tablets, nasal spray, and subcutaneous injection Rapid pain relief without adverse events Dahlöf et al. [28] Most patients would like to continue using zolmitriptan nasal spray Rapid pain relief without adverse events Lipton et al. [29] When selecting a triptan, the rating of efficacy attributes was clearly more important than tolerability or consistency Absence of pain within 1 hour was the most desired treatment outcome for migraine patients Schoenen et al. [30] More patients preferred eletriptan Rapid pain relief without recurrence Lainez et al. [31] More patients preferred rizatriptan 10 mg wafer compared to eletriptan 40 mg tablets Rapid pain relief and return to normal activities Dowson et al. [32] At baseline, most patients indicated a preference for conventional tablets. After trying other formulations with a faster onset of action, most patients no longer preferred conventional tablets

Rapid pain relief
Diez et al. [33] More patients preferred almotriptan 12.5 mg compared to rizatriptan 10 mg Rapid pain relief and return to normal activities Lanteri et al. [34] Patients tended to use triptans and were satisfied with this treatment Freedom from pain and rapid onset of action Bartolini et al. [35] Most of the patients indicated a preference for triptans Rapid pain relief without recurrence Gonzalez et al. [36]. No recurrence of headache Smelt et al. [37] Patients wanted to relieve pain within 30 minutes after treatment, returned to normal activity within 1 hour, and had no recurrence of headache Pain Research and Management 7