Validation of the revised Patient Perception of MigraineQuestionnaire (PPMQ-R): measuring satisfaction with acutemigraine treatment in clinical trials

M Kimel1, R Hsieh1, J McCormack1, SP Burch2 & DA Revicki1

1Center for Health Outcomes Research, United BioSource Corporation, Bethesda, MD and 2GlaxoSmithKline Research and Development,Research Triangle Park, NC, USA

Kimel M, Hsieh R, McCormack J, Burch SP & Revicki DA. Validation of therevised Patient Perception of Migraine Questionnaire (PPMQ-R): measuringsatisfaction with acute migraine treatment in clinical trials. Cephalalgia 2008;28:510–523. London. ISSN 0333-1024

This study was aimed to evaluate in clinical trial settings the psychometricproperties of the revised Patient Perception of Migraine Questionnaire (PPMQ-R), a satisfaction measure for acute migraine treatment. The PPMQ-R wasadministered 24 h post dosing in 1304 migraineurs randomized to two identicalPhase 3, single-attack trials. Reliability, concurrent and construct validity andknown-groups validity were evaluated using Cronbach’s a, Pearson correlationsand analysis of variance, respectively. PPMQ-R scale and Total scores (Efficacy,Functionality and Ease of use) showed very good internal consistency reliability(a 0.84–0.99). Efficacy, Functionality and Total PPMQ-R scores showed large,inverse relationships with migraine pain severity, number of migraine symptomsand work ability (r = -0.62 to -0.75; all P < 0.0001). All scales discriminatedamong migraine pain severity levels (all P < 0.001). The PPMQ-R has sufficientevidence of validity and reliability for measuring patient satisfaction, an impor-tant benchmark of quality and effective care. �Migraine, questionnaire, satisfaction,treatment, validation

Miriam Kimel, PhD, Center for Health Outcomes Research, United BioSourceCorporation, 7101 Wisconsin Avenue, Suite 600, Bethesda, MD 20814, USA. Tel.+ 1 301 654 9729, fax + 1 301 654 9864, e-mail miriam.kimel@unitedbiosource.comReceived 17 April 2007, accepted 30 August 2007

Introduction

Treatment satisfaction, defined as the patient’sevaluation of important attributes associated withthe process and outcomes of the treatment experi-ence, is increasingly assessed in clinical trials andevaluations of disease management programmes(1, 2). For any therapy, key domains associated withtreatment satisfaction have been identified in theliterature and include treatment effectiveness (i.e.symptom relief, speed of onset, duration of effects),discomfort (i.e. bother, side-effects), regimen char-acteristics (i.e. convenience), preference for continu-ing treatment and cost (1–3). These domains areconsistent with attributes identified for migraine-specific therapies to treat acute headache attacks,

which are: rapid pain relief, complete pain relief,consistent pain relief across headaches, ability toreturn to normal functioning, relief of migraine-associated symptoms, reduction in headache recur-rence and minimal adverse effects (4–10).

Although treatment satisfaction measures areoften used in clinical trials, until recently reportsdescribing the development and psychometric vali-dation of these measures have been scarce, limitingclinical study applications and interpretation ofstudy findings. This is particularly true of instru-ments that measure satisfaction specific to migrainetreatments. More recently, however, several well-developed and psychometrically sound measuresof satisfaction with specific treatments (e.g. contra-ception, pain) or general treatment have been

doi:10.1111/j.1468-2982.2007.01524.x

510 © Blackwell Publishing Ltd Cephalalgia, 2008, 28, 510–523

developed (11–14). Treatment satisfaction measureswith evidence of reliability and validity are neededto evaluate migraine therapies in clinical studiesto ensure results are valid and meaningful in thissetting. The revised Patient Perception of MigraineQuestionnaire (PPMQ-R) is one of the few pub-lished questionnaires assessing patient satisfactionwith acute migraine treatment and reporting on thedevelopment process and psychometric evaluation(15–17).

The PPMQ-R is a 32-item instrument designed tomeasure patient satisfaction with acute migrainetreatment. It measures satisfaction with efficacy,function, ease of use, cost and tolerability of side-effects (i.e. Efficacy, Functionality, Ease of Use, Costand Tolerability scales). The psychometric proper-ties of the PPMQ-R were previously evaluated in anout-patient population of adult patients from 50primary care and neurology specialty clinics acrossthe USA (n = 200) (16). Previous research has shownthat the measure had good reliability and validitycharacteristics in both single-attack and multiple-attack evaluations. In addition, the PPMQ-R wasresponsive to changes in clinical status in multiple-attack evaluations.

Currently, the psychometric properties of thePPMQ-R have not been evaluated in a clinical trialsetting. There are also questions as to whether thefull range of adverse events for migraine treatmentis being captured by the Tolerability domain. Theobjective of this study was to evaluate the psycho-metrics properties of the PPMQ-R in a clinical trialsetting and the Tolerability scale’s coverage ofreported adverse events.

Materials and methods

Psychometric evaluation study

This analysis used data from two identical Phase IIItrials [Trial 1 (TRX101998) and Trial 2 (TRX101999)]for a fixed-dose, single-tablet combination ofsumatriptan 85 mg formulated with RT Technolo-gyTM and naproxen sodium 500 mg. Subjects wereeligible to participate in the trials if they (i) werebetween 18 and 65 years of age; (ii) were male orfemale (females of non-childbearing potential or ofchild-bearing potential with a negative pregnancytest at screen and agreement to several conditions);(iii) had at least a 6-month history that met 2004International Headache Society (HIS) Criteria formigraine with aura (ICHD-II 1.2.1) or migrainewithout aura (ICHD-II 1.1); (iv) experienced two tosix migraine attacks per month in the 3 months

prior to screening; (v) typically experienced mod-erate to severe migraine pain preceded by anidentifiable mild pain phase; (vi) were able to dis-tinguish between mild migraine pain and otherheadache types; (vii) were able to read, compre-hend and complete subject diaries and understandthat they must treat their migraine during the mildpain phase; and (viii) were able and willing to givewritten informed consent to participate in the study.

In each single-attack trial, approximately 600subjects were randomized to receive sumatriptan85 mg/naproxen sodium 500 mg or placebo, to betaken orally within 1 h of onset of migraine headpain if the pain was mild at the onset and while thepain remained mild. At the screening visit, demo-graphic data were collected and subjects completedthe Headache Impact Test (HIT)-6 (Table 1). Using adiary, subjects recorded details of their migraineattack. Migraine pain severity and the presence ofmigraine-associated symptoms were recorded atdosing and 30 min and 1, 2 and 4 h after the firstdose of the study medication. Work ability wasrecorded at dosing with the study medication and2 and 4 h after dosing, while use of additionalmedications and migraine pain reoccurrence wererecorded throughout the study. The PPMQ-R andproductivity questionnaires were completed 24 hafter dosing with the study medication. Clinicalvariables, including adverse events, were recordedby clinical personnel throughout the study.

The psychometric analyses combined data fromboth treatment groups and were performed blindedto treatment group status. Repeated observationsover time for each subject (e.g. migraine pain sever-ity) were not aggregated.

Clinical and patient-reported outcome measures

Patient perception migraine questionnaireThe PPMQ-R consists of 29 questions that assessa patient’s satisfaction with migraine medicationin terms of its Efficacy (11 items), Functionality(four items), Ease of use (two items) and Cost (twoitems), as well as the degree to which side-effectswere tolerated (Tolerability; 10 items). In addition,three global items measuring subject satisfaction interms of medication effectiveness, side-effects andoverall satisfaction are included. Items that evaluatetreatment satisfaction are scored on a seven-pointLikert-type scale from 1 (very satisfied) to 7 (verydissatisfied); whereas items that evaluate tolerabil-ity of side-effects (i.e. bother due to side-effects) arescored on a five-point Likert-type scale from 1 (notat all) to 5 (extremely). Data from the PPMQ-R are

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analysed as four subscale scores (Efficacy, Function-ality, Ease of use and Tolerability) and a Total score(composite of the Efficacy, Functionality and Ease ofuse subscales). Scale scores are transformed torange from 0 to 100, with higher scores indicatingbetter satisfaction or tolerability. For this study, thetwo items that comprise the cost subscale were notused because subjects did not pay for the studymedication; therefore, 27 questions and three globalitems were used.

Migraine diary

The details of the single migraine attack were cap-tured in a self-administered subject diary. Specifi-cally, subjects recorded data on headache painseverity (none, mild, moderate, severe); the pres-ence of migraine symptoms [nausea, vomiting, sen-sitivity to light and sound, neck pain/discomfort,sinus (facial) pain/pressure]; ability to work orperform normal or usual activities (normal, mildlyimpaired, moderately impaired, severely impaired,required bedrest); the presence of a recurrentmigraine pain; the time and severity level (mild,moderate, severe) of pain recurrence; and addi-tional medications taken, including the date andtime taken and the primary reason for taking.

Productivity questionnaireThe productivity questionnaire included: (i) thenumber of hours a subject missed from work andnon-work activities; (ii) the number of hours asubject worked with symptoms and continued toparticipate in non-work activities with symptoms;and (iii) the subject’s rating of effectiveness while

continuing work and non-work activities withsymptoms during the 24 h after taking the studydrug.

Demographic and clinical characteristicsDemographic and clinical characteristics such asthe IHS headache classification (migraine with andwithout aura), migraine history (e.g. number ofmigraine attacks typically experienced per 30-daycalendar month), previous migraine treatments andsatisfaction with previous treatments were collectedat screening. Information on non-serious adverseevents (AEs) and serious adverse events (SAEs)were collected throughout the study and included:description of event, start and stop date, outcome,maximum intensity, action taken with the studymedication as a result of the AE or SAE, subjectwithdrawal from the study, and the relationship ofthe AE or SAE to the study medication (i.e. reason-able possibility).

Headache impact testThe HIT-6 consists of six questions used to measurethe impact headaches have on a person’s ability tofunction at work, school, home, or social situations.Scores range from 36 to 78, with higher scoresindicating a greater impact of headaches on theperson’s life (18).

Psychometric analysis

Analyses were performed to examine item charac-teristics, factor structure and scoring, reliability, andvalidity (concurrent and construct) of the PPMQ-Rin measuring satisfaction with an acute migraine

Table 1 Timetable for measures used in Trials 1 and 2

MeasuresBaseline/screening

24 h beforedosing At dosing

Time after dosing with investigational product

30 min 1 h 2 h 4 h 24 h

Demographics XMedication history XMigraine history XHIT-6 XMigraine pain severity X X X X XRecurrent pain severity ← 2–24 h after dosing* →Migraine symptoms X X X X XWork ability X X XAdditional medications ← Throughout the 24-h periods before after dosing →Adverse events ← Throughout entire study period →PPMQ-R XProductivity X

*During the 24 h following dosing with investigational product if migraine pain returned.

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treatment for a single attack. The data from bothtrials were combined for the psychometric analysisof the PPMQ-R and the statistical analyses wereperformed blinded to treatment group. All patientsrandomized to treatment were included in thisanalysis.

Sociodemographic characteristicsSample sociodemographic characteristics at screen-ing such as age, gender and race were summarized(e.g. means, frequencies) for the study sample todescribe the sample population. Clinical factorssuch as medication characteristics (e.g. previous/current treatment for migraine) and migraine char-acteristics (e.g. headache type, migraine history)were also summarized for the screening evaluation.

Item characteristics and factor structureTo evaluate whether PPMQ-R items are capturingthe full range of response options and the associa-tions between items, characteristics of individualitems were examined by calculating the mean,minimum possible and maximum possible response(i.e. floor and ceiling effects), percent missing anditem–item correlations.

Confirmatory factor analysis was used to sub-stantiate the findings on factor structure and itemgroupings based on previous research conductedon the PPMQ-R (16) and was performed withMplus software (Version 4.1). To determine theacceptability of the factor structure and item load-ings, fit indices were evaluated for two models—atwo-factor (Efficacy/Functionality and Ease of use)and a three-factor (Efficacy, Functionality and Easeof use) solution. The following fit indices wereused to assess the fit of each model: Bentler’s (19)comparative fit index (CFI; values > 0.90 representacceptable fit), root mean square error of approxi-mation (RMSEA; values > 0.05 to � 0.08 representadequate fit) (20) and standardized root meansquare residual (SRMR; values < 0.05 representacceptable fit) (21).

ReliabilityInternal consistency reliability of multi-item scaleswas assessed using Cronbach’s a, with values� 0.70 considered acceptable for group-level com-parisons (22, 23).

ValidityCorrelations between the PPMQ-R and other mea-sures that are considered conceptually or clinicallyrelated were evaluated, including pain severity,number of symptoms, work ability, recurrence of

migraine pain, number of additional medicationstaken and productivity. Concurrent validity wassupported when a specific scale was substantiallycorrelated (> 0.40) with a generic scale measuringthe same or a similar concept. Conversely, scalesmeasuring different concepts should be lessstrongly correlated (< 0.40). For interpretation,guidelines suggested by Cohen (24) were used,where absolute correlation values between 0.10 and0.29 are considered small, 0.30–0.49 are consideredmedium, and 0.50–1.00 are considered large.

The ability of the PPMQ-R scores to discriminatebetween groups of patients according to clinicalseverity was assessed using analysis of variance(ANOVA) with Scheffe’s post hoc comparisons toevaluate mean differences between three or moregroups. Clinical severity criteria were based onfindings from the descriptive analysis (e.g. painseverity 4 h after dose, work ability 4 h after dose).Specifically, ANOVAs were used to assess the rela-tionship between treatment satisfaction based onthe PPMQ-R and the following: migraine painseverity (mild, moderate and severe), work ability(normal, mild, moderate, severe, requires bedrest),number of symptoms (0, 1–2, � 3), productivity forwork and non-work activities (percent effectivenessat or below the median vs. percent effectivenessabove the median), and additional medications totreat migraine pain (yes, no).

Completeness of the Tolerability scaleCompleteness of the Tolerability scale was assessedby cross-classifying side-effects listed in theTolerability domain with the (i) severity of AEs(mild, moderate, severe) and (ii) AE ratings relatedto study medication (possibly related to studymedications—yes/no).

Results

Sample characteristics

A total of 1304 patients suffering from migraineattacks participated in this study. Patient character-istics are summarized in Table 2. Study participantswere primarily White (85.5%), women (87.8%), withan average age of 40 years. On average, participantswere 22.5 years old when first experiencingmigraine attacks. Based on a 6-month history thatmeets IHS criteria for headache with or withoutaura at screening, the majority of participants hadexperienced migraine without aura (80.6%), whilejust over a third (33.6%) had experienced migrainewith aura. Since patients can experience both types

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of migraine headaches, these categories are notmutually exclusive. At screening, patients reportedthat they had experienced an average of 3.8migraine attacks per month during the past yearand that they averaged 7.3 days per month withany headache. Participants scored an average 53.9points on the HIT-6, indicating that their migraineshad some impact on their lives.

The most commonly used medications to treatacute migraine attacks—prior to enrolment in thetrials—were sumatriptan (39.5%) and over-the-counter non-steroidal anti-inflammatory drugs thatdo not contain naproxen (43.9%). Of all patients inthe study (n = 1304), 53% reported that they weresatisfied with sumatriptan, which was the highestrate of satisfaction among the 12 medications ormedication classes listed.

At the time patients initiated treatment for theirattack, most (74.2%; 968 of 1304) rated their average

migraine pain as mild (Table 3). These patientsreported an average of 2.3 migraine symptoms perattack, having experienced light sensitivity (60.2%),sound sensitivity (52.8%) and neck pain or discom-fort (52.0%) most often. Approximately three-quarters of patients experienced some levelof impairment (mildly impaired to requiringbedrest) in their ability to perform work or usualactivities.

Improvements in pain and ability to performwork or usual activities were observed after treat-ment, with more than two-fifths of patients report-ing no migraine pain (40.8%) and no workimpairment (45.4%) 4 h after dosing with studymedication (sumatriptan 85 mg/naproxen sodiumand placebo groups combined). On average,patients experienced one less symptom 4 h afterdosing. Light sensitivity, sound sensitivity andneck pain or discomfort—the three most commonsymptoms—were reduced by 34.1%, 29.3% and27.4%, respectively. Compared with being as effec-tive as usual in performing activities (i.e. 100%effective), patients reported being 71.3% effectiveperforming paid work activities and 62.2% effectiveperforming activities outside of paid work 24 hafter treatment. The clinical and health outcomeeffects of sumatriptan 85 mg/naproxen sodiumcompared with placebo are reported elsewhere(25, 26).

Of 576 patients who reported being pain free at2 h, 78% did not have a return of migraine pain2–24 h after dosing (i.e. 22% recurrence rate).Approximately half of all patients took an addi-tional medication to treat their migraine attack.

PPMQ-R item and subscale characteristics

Item characteristicsScores for PPMQ-R items rated on the seven-pointsatisfaction scale (i.e. items 1A-1Q; 3A-3C) coveredthe full range of response options, with mean scoresranging from 2.0 (satisfied) to 4.3 (neither satisfiednor dissatisfied). The percentages of patientsscoring at the floor (the lowest possible score: ‘verydissatisfied’) ranged from 1.6% (how convenient themedication is to use) to 23.1% (how well the medi-cation prevents the need for other medications totreat the migraine attacks). The percentages ofpatients scoring at the ceiling (the highest possiblescore: ‘very satisfied’) ranged from 7.6% (how fastthe medication relieves other migraine symptoms)to 38.1% (how convenient the medication is to use).Skewness statistics for the individual PPMQ-Ritems ranged from -0.0004 to 0.198 for the

Table 2 Demographics at screening for all eligible patients

CharacteristicsTotal sample(n = 1304)

Age (years), mean (S.D.) 40.1 (11.09)Gender, n (% female) 1145 (87.8)

Race, n (%)White 1115 (85.5)Black 125 (9.6)Asian 17 (1.3)American Indian/Alaskan Native 32 (2.5)Native Hawaiian/other Pacific Islander 4 (0.3)Other 5 (0.4)Missing 6 (0.5)

Ethnicity, n (%)Hispanic or Latino 107 (8.2)Not Hispanic or Latino 1197 (91.8)

Migraine characteristicsMigraine without aura, n (% yes) 1051 (80.6)Migraine with aura, n (% yes) 438 (33.6)Number of migraine attacks experienced

per month during the past year, mean(range)

3.8 (1–24)

Age of onset of migraine attacks, mean(S.D.)

22.5 (10.7)

Number of days with any headacheexperienced per month during thepast year, mean (range)

7.3 (1–30)

Number of days without any headacheexperienced per month during thepast year, mean (range)

22.7 (0–30)

HIT-6*, mean (S.D.) 53.9 (7.0)

*Scores range from 36 to 78, with higher scores indicatinga greater impact of headaches on the person’s life.

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satisfaction items and from 0.090 to 0.112 for theoverall satisfaction items. Except for Ease of useitems, scores across response categories appear tobe relatively evenly distributed.

Scores for PPMQ-R items rated on the five-pointtolerability scale (i.e. items 2A-2J) covered thefull range of response options, with mean scoresranging from 1.1 (not at all bothered) to 1.6 (slightly

bothered). Floor effects, reporting ‘extremely [both-ered]’, were low and ranged from 0.5% (nervous-ness, chest pain) to 2.5% (nausea). In contrast, highceiling effects, reporting ‘not at all [bothered]’, wereobserved for all items, ranging from 55.9% (tired ordrowsy) to 81.0% (vomiting). Skewness statisticsfor individual tolerability items ranged from 1.807to 5.982. Scores across response categories were not

Table 3 Migraine attack characteristics (n = 1304)

Time point

At time of dosing 30 min after dose 1 h after dose 2 h after dose 4 h after dose

Pain severity n (%)None 1 (0.1) 41 (3.1) 160 (12.3) 378 (29.0) 532 (40.8)Mild 968 (74.2) 621 (47.6) 508 (39.0) 357 (27.4) 253 (19.4)Moderate 119 (9.1) 399 (30.6) 357 (27.4) 236 (18.1) 163 (12.5)Severe 21 (1.6) 43 (3.3) 76 (5.8) 129 (9.9) 138 (10.6)Missing 195 (15.0) 200 (15.3) 203 (15.6) 204 (15.6) 218 (16.7)

Nausea n (%)Yes 338 (25.9) 250 (19.2) 210 (16.1) 246 (18.9) 195 (15.0)No 763 (58.5) 520 (39.9) 556 (42.6) 841 (64.5) 874 (67.0)Missing 203 (15.6) 534 (41.0) 538 (41.3) 217 (16.6) 235 (18.0)

Vomiting n (%)Yes 17 (1.3) 10 (0.8) 11 (0.8) 21 (1.6) 24 (1.8)No 1081 (82.9) 755 (57.9) 749 (57.4) 1061 (81.4) 1039 (79.7)Missing 206 (15.8) 539 (41.3) 544 (41.7) 222 (17.0) 241 (18.5)

Light sensitivity n (%)Yes 785 (60.2) 508 (39.0) 431 (33.1) 443 (34.0) 340 (26.1)No 315 (24.2) 256 (19.6) 334 (25.6) 642 (49.2) 729 (55.9)Missing 204 (15.6) 540 (41.4) 539 (41.3) 219 (16.8) 235 (18.0)

Sound sensitivity n (%)Yes 688 (52.8) 452 (34.7) 376 (28.8) 394 (30.2) 307 (23.5)No 414 (31.7) 316 (24.2) 386 (29.6) 690 (52.9) 762 (58.4)Missing 202 (15.5) 536 (41.1) 542 (41.6) 220 (16.9) 235 (18.0)

Neck pain/discomfort n (%)Yes 678 (52.0) 441 (33.8) 360 (27.6) 432 (33.1) 321 (24.6)No 421 (32.3) 324 (24.8) 397 (30.4) 652 (50.0) 744 (57.1)Missing 205 (15.7) 539 (41.3) 547 (41.9) 220 (16.9) 239 (18.3)

Sinus pain/pressure n (%)Yes 503 (38.6) 335 (25.7) 280 (21.5) 305 (23.4) 233 (17.9)No 598 (45.9) 433 (33.2) 486 (37.3) 782 (60.0) 839 (64.3)Missing 203 (15.6) 536 (41.1) 538 (41.3) 217 (16.6) 232 (17.8)

Number of migraine symptoms*Mean (S.D.) 2.3 (1.6) 1.5 (1.7) 1.3 (1.6) 1.4 (1.7) 1.1 (1.6)

Work ability n (%)Normal 128 (9.8) – – 385 (29.5) 592 (45.4)Mildly impaired 633 (48.5) – – 356 (27.3) 220 (16.9)Moderately impaired 265 (20.3) – – 221 (16.9) 136 (10.4)Severely impaired 39 (3.0) – – 79 (6.1) 68 (5.2)Required bed rest 45 (3.5) – – 65 (5.0) 86 (6.6)Missing 194 (14.9) – – 198 (15.2) 202 (15.5)

*Symptoms include nausea, vomiting, light sensitivity, sound sensitivity, neck pain/discomfort, sinus pain/pressure.

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evenly distributed, since not everyone experiencedside-effects.

Evaluation of structural validityConfirmatory factor analysis of the PPMQ-R satis-faction items showed evidence for both a two- andthree-factor model: for the three-factor model [Effi-cacy (11 items), Functionality (4 items) and Ease ofuse (2 items)], loadings for all items within eachfactor exceeded 0.40, with the majority being > 0.90(range 0.880–0.995). Fit indices were as follows:CFI = 0.922, RMSEA = 0.148 [90% confidence inter-val (CI) 0.143, 0.153] and SRMR = 0.027. The cor-relation between the Efficacy and Functionalityfactors was 0.938 (Table 4).

Similar loadings were observed for the two-factormodel [Efficacy/Functionality (15 items) and Easeof use (two items)], with the majority being > 0.90(range 0.829–0.958). Fit indices were as follows:CFI = 0.978, RMSEA = 0.081 (90% CI 0.076, 0.086)and SRMR = 0.013.

The final scoring algorithm for the 27 corePPMQ-R items therefore consisted of four scalescores (Efficacy, Functionality, Ease of use andTolerability). Each scale score is calculated bysumming the value of individual items within ascale. A Total score, representing the average ofthe Efficacy, Functionality and Ease of usescales, also can be calculated. All scale scoreswere transformed to a 0–100 scale, with higher

Table 4 Confirmatory factor analysis of PPMQ-R at 24 h: factor loading for ‘satisfaction’ items

Item

PPMQ-R ‘satisfaction’ scales

Three factors* Two factors

Efficacy Function Ease of useEfficacy/function

Easeof use

1a. How well the medication relieves migraine pain 0.956 – – 0.949 –1b. How well the medication relieves other migraine

symptoms0.903 – – 0.893 –

1c. How fast the medication relieves migraine pain 0.944 – – 0.942 –1d. How fast the medication relieves other migraine

symptoms0.907 – – 0.898 –

1e. The number of doses needed to relieve migraine pain 0.935 – – 0.931 –1f. How consistently the medication relieves migraine

pain0.940 – – 0.935 –

1g. How consistently the medication prevents pain fromcoming back

0.880 – – 0.865 –

1h. How long the medication relieves migraine painbefore you need to take another dose

0.930 – – 0.921 –

1i. How well the medication relieves migraine pain andother symptoms regardless of whenduring the headache you take the medication

0.936 – – 0.933 –

1j. How well the medication prevents the need for othermedications to treat the migraine

0.946 – – 0.944 –

1k. How fast the medication allows you to return toyour usual daily activities

0.953 – – 0.963 –

1l. How productive you are in performing your usualdaily activities

– 0.980 – 0.944 –

1m. Ability to participate in your usual social activities – 0.995 – 0.940 –1n. Ability to participate in your usual family activities – 0.991 – 0.938 –1o. How well the medication reduces the frustration

associated with your migraine headaches– 0.933 – 0.958 –

1p. How easy the medication is to use – – 0.932 – 0.9261q. How convenient the medication is to use – – 0.824 – 0.829

*Correlation of Efficacy and Function scales = 0.939.Items 3a-3c are single-item scales and are not included in the analysis.For three-factor solution: comparative fit index (CFI) = 0.922; root mean square error of approximation (RMSEA) = 0.148. For

two-factor solution: CFI = 0.978; RMSEA = 0.081.

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scores reflecting more satisfaction or betterTolerability.

Subscale characteristicsEach subscale was scored on a 0–100 scale, withhigher scores reflecting greater satisfaction or Tol-erability. Forty per cent of patients scored at theceiling (100% satisfaction or tolerability) for theEase of use and Tolerability scales, with the meanscores being 82.4 and 92.1, respectively. In addition,none of the patients scored at the floor (0% toler-ability) for the Tolerability scale. Except for corre-lations with the Tolerability scale (Tolerability andEfficacy; Tolerability and Functionality), all subscaleto subscale correlations were statistically significant(all P < 0.05), ranging from 0.08 (Tolerability andEase of use) to 0.94 (Efficacy and Functionality)(Table 5). Total to subscale correlations were alsosignificant (all P < 0.0001), except for the Tolerabilityscale, ranging from 0.65 (Ease of use) to 0.96(Efficacy).

Reliability

The four PPMQ-R scale scores and Total score dem-onstrated good internal consistency reliability(Cronbach’s a= 0.84–0.99) 24 h after treatment(Table 6).

Validity

Concurrent and construct validityTable 7 summarizes the correlations between thePPMQ-R and indicators of severity such asmigraine pain severity, the number of migrainesymptoms and work ability (i.e. concurrent valid-ity). All PPMQ-R scores were negatively correlatedwith migraine pain ratings at 4 h after the migraineattack (P < 0.0001). Migraine pain, number ofmigraine symptoms, work ability and the numberof additional medications to treat migraine painhad large, significant negative correlations with theEfficacy and Functionality subscales and the Totalscores (e.g. the less pain, symptoms, impairment, ormedications, more treatment satisfaction), with cor-relations ranging from -0.49 to 0.75 (all P < 0.0001).Percent effectiveness at work (i.e. paid work) andhours missed from non-work activities hadmedium, significant correlations with the Efficacyand Functionality subscales (r = 0.36–0.42; allP < 0.0001). The Ease of use scale was most highlycorrelated with migraine pain severity (r = 0.34,P < 0.0001), whereas the Tolerability scale was mosthighly correlated with percent effectiveness at work(r = 0.29, P < 0.0001).

In addition, the three global satisfaction items ofthe PPMQ-R (Overall Satisfaction, Overall Efficacy

Table 5 PPMQ-R subscale to subscale correlations† 24 h after investigational product

Efficacy Functionality Ease of use Tolerability Total

Efficacy 1.00 0.94***n = 1107

0.44***n = 1107

-0.03n = 1106

0.96***n = 1107

Functionality 1.00 0.44***n = 1107

0.04n = 1106

0.95***n = 1107

Ease of use 1.00 0.08*n = 1106

0.65***n = 1107

Tolerability 1.00 0.03n = 1106

*P < 0.05; **P < 0.001; ***P < 0.0001.†Pearson product moment correlations.

Table 6 Distributional and scale characteristics of the PPMQ-R

Scale mean (S.D.) Crohnbach’s a % Scores at scale floor % Scores at scale ceiling Skewness

Efficacy 48.3 (34.3) 0.986 16.1 3.7 -0.098Functionality 47.9 (34.9) 0.986 19.0 9.4 -0.023Ease of use 82.4 (22.0) 0.868 1.9 39.7 -1.707Tolerability 92.1 (12.2) 0.841 0.0 39.3 -2.620Total 59.5 (26.8) 0.984 1.4 3.3 -0.184

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and Side-effects) had significant correlations witheach PPMQ-R subscale and Total score (r = -0.19–0.93; all P < 0.0001) (i.e. construct validity). In par-ticular, the Overall Satisfaction and Efficacy itemshad large correlations with the Efficacy and Func-tionality subscales and the Total scores (rangingfrom 0.89 to 0.93; all P < 0.0001). For the Tolerabilityscale, the highest correlation was with the globalSide-effects item (r = 0.28, P < 0.0001).

Known groups validityAll PPMQ-R scale scores discriminated among painseverity levels 4 h after dosing, with those experi-encing severe pain generally having the lowestPPMQ-R satisfaction scores (most P < 0.0001)(Fig. 1). PPMQ-R scores differed significantlyamong patients categorized based on their ability towork 4 h after treatment for their migraine attack(most P < 0.0001) (Fig. 2). Except for the Tolerability

scale, all PPMQ-R scores also differentiatedbetween the number of migraine symptoms 4 hafter treatment (all P < 0.0001), with those experi-encing more symptoms reporting the lowest scores(least satisfaction). In general, PPMQ-R scale scoresand Total scores were highest for patients who werenot impaired and lowest for those who requiredbedrest following treatment initiation.

Adverse events

Of 1304 patients, 114 experienced 180 AEs. Therewere no SAEs reported. Ninety-three of the 180 AEsreported (51.7%) were categorized as one of the 10side-effects included in the PPMQ-R Tolerabilityscale (Table 8). Nausea was the most frequentlyreported side-effect that was captured in the Toler-ability scale, occurring 34 times (18.9% of all AEs).Being tired or drowsy, experiencing dizziness,

Table 7 Concurrent and construct validity at 24 h: correlation between PPMQ-R, migraine severity and symptoms at 4 h,work ability and the productivity questionnaire

Scale

PPMQ-R†

Efficacy Functionality Ease of use Tolerability Total

Pain severity‡ -0.75*** -0.72*** -0.34*** 0.15*** -0.73***Number of migraine symptoms‡ -0.64*** -0.62*** -0.28*** -0.02 -0.62***Work ability‡ -0.68*** -0.69*** -0.27*** 0.07* -0.68***

Recurrence§Migraine pain returned (yes/no) -0.40*** -0.35*** -0.16*** 0.02 -0.37***Number of hours after

investigational product taken0.36*** 0.33*** 0.09 -0.07 0.33***

Migraine pain severity -0.34*** -0.35*** -0.07 0.08 -0.33***

Number of additional medicationstaken after study medication totreat migraine pain

-0.51*** -0.49*** -0.21*** 0.03 -0.49***

Work productivity¶Hours missed -0.11* -0.15* -0.09 -0.16* -0.13*Hours continued activity -0.13* -0.09 -0.05 0.08 -0.10*Percent effective 0.36*** 0.42*** 0.24*** 0.29*** 0.39***

Non-work productivity¶Hours missed -0.37*** -0.38*** -0.17*** -0.09* -0.37***Hours continued activity -0.22*** -0.15** -0.08 0.10* -0.18***Percent effective 0.27*** 0.34*** 0.15** 0.13* 0.31***

PPMQ-R global satisfaction itemsOverall 0.92*** 0.89*** 0.44*** -0.19*** 0.90***Efficacy 0.93*** 0.90*** 0.43*** -0.21*** 0.91***Side-effects 0.35*** 0.39*** 0.42*** 0.28*** 0.42***

*P < 0.05; **P < 0.001; ***P < 0.0001.†Pearson product moment correlations or Spearman rank correlations.‡4 h after treating with study medication.§Between 2 and 24 h after treating with study medication.¶24 h after treating with study medication.

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having chest pains or pressure, and having a drymouth were the next most frequently reported side-effects that were captured in the Tolerability scale(7.8%, 6.7%, 5.6% and 5.0%, respectively, for allAEs). The most frequently reported side-effects thatwere not captured by the Tolerability scale were:experiencing sensations or pain (e.g. pressure, para-esthesia); having an infection; or experiencing ear,nose and throat symptoms (e.g. congestion) (21.7%,9.4% and 4.4%, respectively).

Of the 93 reported AEs captured by the Tolerabil-ity scale, the majority were rated as (i) either mild(48.4%) or moderate (41.9%) in severity and (ii)

having a reasonable possibility of a relationship tothe study medication (63.8%). Forty-six (36.2%) ofthe AEs not included in the PPMQ-R were consid-ered as having a reasonable possibility of a rela-tionship to the study medication.

Discussion

The PPMQ-R was specifically designed to measuresatisfaction with pharmacological therapy inpatients who experience migraine headaches. Pre-vious work evaluating the psychometric propertiesof the PPMQ-R in a prospective study of 200

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Figure 1 PPMQ-R scores discriminate among pain severity levels. **P < 0.0001, ANOVA for difference among pain severitylevels. *P < 0.01, ANOVA for difference among pain severity levels.

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Figure 2 PPMQ-R scores discriminate among work ability levels. **P < 0.0001, ANOVA for difference among work abilitylevels. *P < 0.01, ANOVA for difference among work ability levels.

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migraine patients visiting neurologists andprimary care clinics suggests that the PPMQ-R hasfive scales measuring satisfaction: Efficacy, Func-tionality, Ease of use, medication cost and toler-ability of medication side-effects. The PPMQ-Rscale scores and Total score demonstrated goodreliability (internal consistency and test–retest),validity (construct and discriminant) and respon-siveness to change (16). A difference of five points

was recommended as the minimally important dif-ference (MID) for the Efficacy, Functionality andEase of use scale scores, as well as the PPMQ-RTotal score (16). Findings from the current study,which assessed treatment satisfaction 24 h afterdosing, provides further confirmation of the psy-chometric characteristics of the PPMQ-R (i.e. factorstructure, internal consistency reliability and valid-ity) in a clinical trial setting.

Table 8 Cross classification: reported adverse event (AE) (categorized based on PPMQ tolerability items) by relationship tostudy medication

AE*

Reasonable possibility of relationship of AE to study medication

Yes (n = 127) No (n = 53)

PPMQ-R itemsChest pains or pressure† 10 (7.9%) 0 (0.0%)Cognitive ability‡ 1 (0.8%) 1 (1.9%)Dizziness§ 11 (8.7%) 1 (1.9%)Tired or drowsy¶ 13 (10.2%) 1 (1.9%)Nausea†† 31 (24.4%) 3 (5.7%)Nervousness‡‡ 5 (3.9%) 2 (3.8%)Affects on heart rate§§ 2 (1.6%) 1 (1.9%)Vomiting 2 (1.6%) 0 (0.0%)Sleepiness 0 (0.0%) 0 (0.0%)Dry mouth 6 (4.7%) 3 (5.7%)

Total PPMQ-R items 81 (63.8%) 12 (22.6%)

Not included in PPMQ-RBlood pressure increased 1 (0.8%) 1 (1.9%)Depression 0 (0.0%) 1 (1.9%)Diarrhoea 1 (0.8%) 0 (0.0%)Dyspnoea 3 (2.4%) 0 (0.0%)Emotional disorder 0 (0.0%) 1 (1.9%)ENT symptoms¶¶ (e.g. congestion) 4 (3.1%) 4 (7.5%)Excoriation 0 (0.0%) 1 (1.9%)Flushing 1 (0.8%) 0 (0.0%)Hypertension 0 (0.0%) 1 (1.9%)Ill-defined disorder 0 (0.0%) 1 (1.9%)Infection (e.g. laryngitis, sinusitis) 0 (0.0%) 17 (32.1%)Musculoskeletal (e.g. strain) 3 (2.4%) 2 (3.8%)Pulmonary congestion 0 (0.0%) 1 (1.9%)Seasonal allergy 0 (0.0%) 1 (1.9%)Sensation or pain 29 (22.8%) 10 (18.9%)Swelling face 1 (0.8%) 0 (0.0%)Throat tightness 3 (2.4%) 0 (0.0%)

Total non-PPMQ-R items 46 (36.2%) 41 (77.4%)

*For AEs that occurred at any time during the trial; n = 180.†Included chest discomfort and chest pain AE terms.‡Included confusional state and mental impairment AE terms.§Included dizziness and vertigo AE terms.¶Included fatigue and somnolence AE terms.††Included dyspepsia and nausea AE terms.‡‡Included agitation, anxiety, nervousness and psychomotor hyperactivity AE terms.§§Included heart rate increased and palpitations AE terms.¶¶ENT, Ear, nose and throat.

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Individual responses for the satisfaction-relateditems for the Efficacy and Functionality subscalesdid not demonstrate significant ceiling or flooreffects. The responses for the two questions onsatisfaction with Ease of use demonstrated ceilingeffects. However, these results may reflect the con-venience of using oral medications and the popu-larity of this formulation among the study sample.Given that skewed responses were a commonproblem in most previously published treatmentsatisfaction measures (i.e. more positive ratings ofsatisfaction) (2, 3), these results for the PPMQ-R areencouraging. The responses for the items in theTolerability subscale were highly skewed and dem-onstrated large ceiling effects (i.e. little bother withthe listed side-effects). This finding was not unex-pected, given that only a small number of patientsin this study experienced side-effects (8.7%). ThePPMQ-R subscale and Total scores have acceptableceiling and floor effects, except for Ease of use andTolerability. For example, the Total score had only1.4% of scores at the lowest score and 3.3% at thehighest possible score.

The confirmatory factor analyses provide evi-dence supporting either a two-factor or three-factorsolution for the Efficacy, Functionality and Ease ofuse domain scores. These factor analysis resultsare consistent with earlier research, where a strongcorrelation was observed between the Efficacy andFunctionality scales (r = 0.87) (16). Although thetwo-factor solution fits these data somewhat better,there are reasons for keeping the Efficacy and Func-tionality subscales separate. Previous research ontreatment satisfaction suggests differentiating effec-tiveness and functional impact (1, 2), and thesetwo outcomes provide more comprehensive under-standing of patient perceptions of satisfaction. Thequalitative data from migraine patients also sug-gested that functional impact and efficacy wereconsidered separate and conceptually distinctattributes. Finally, it is important, and of interestto clinicians, to be able to understand differencesbetween satisfaction with efficacy and function.Although these two satisfaction concepts areexpected to be strongly correlated, they do capturedifferent aspects of satisfaction with migraine treat-ment. Regardless, the confirmatory factor analysesalso provide strong support for combining the threesubscales into a Total score. Future research needsto explore the interrelationship between satisfactionwith the effectiveness of treatment and satisfactionwith its functional impact.

The PPMQ-R demonstrated acceptable internalconsistency reliability for group level comparisons.

The findings indicated that the subscale and Totalscores are internally consistent (Cronbach’s a range0.84–0.99). The reliability results were comparableto those found in Revicki et al. (16).

The PPMQ-R scores discriminated amongvarious levels of pain and work and usual activityimpairment. Except for Tolerability, significant dif-ferences in satisfaction scores were observed amongpatient-rated migraine pain severity levels for allPPMQ-R subscale and Total scores. The resultsdemonstrated that patients with less pain weremore satisfied with their treatment. Similar findingswere observed for differences in satisfaction scoresamong levels of work ability and levels of effective-ness for paid work and non-paid activities for allPPMQ-R subscale and Total scores. Patients report-ing less work and activity impairment were moresatisfied with their treatment. These findings areconsistent by previous work on the PPMQ-R (16).

This study has provided evidence supporting theconcurrent and construct validity of the PPMQ-R inmigraine patients and findings were generally con-sistent with the previous work for the PPMQ-R.Except for Tolerability, all the subscale scoreswere significantly related to reports of migrainepain severity, number of migraine symptoms, workability, migraine recurrence and the need for addi-tional medications. The PPMQ-R subscale and Totalscores, except for Tolerability, varied significantlyby number of symptoms, where patients with fewersymptoms 4 h after treatment reported higher treat-ment satisfaction. The PPMQ-R subscale and Totalscores also varied significantly by pain severity,where patients reporting less pain severity alsoreported more satisfaction with treatment. The rela-tionship between migraine symptoms and PPMQ-Rscores suggests that this measure of treatment sat-isfaction may be sensitive to outcomes in clinicaltrials. In addition, the subscale and Total scoreswere significantly associated with work impairmentlevels, with those patients with the most impair-ment reporting the least treatment satisfaction.

The PPMQ-R global satisfaction items (Side-effects, Overall efficacy and Overall satisfaction)were not included in the subscale scoring of thePPMQ-R. However, strong correlations wereobserved between these items and the PPMQ-Rsubscale and Total scores. For example, the globalrating of satisfaction with efficacy was correlated0.93 with Efficacy subscale scores and 0.91 with theTotal score on the PPMQ-R. Correlations betweenthe global rating of satisfaction with side-effectsand the subscale and Total scores were lower thancorrelations between other global ratings and the

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subscale and Total scores, perhaps due to the smallnumber of AEs reported. These results suggest thatthe single-item scores may be useful as simplemeasures of treatment satisfaction for clinical prac-tice or other studies where briefer measures may beneeded. For clinical trial situations, it is recom-mended that the complete PPMQ-R be used, sincemulti-item subscales have better reliability, validityand responsiveness.

Findings from the AE analyses suggest that thePPMQ-R captures the side-effects most often asso-ciated with migraine treatment. Although AEs werenot often reported, half of those reported werecaptured by the PPMQ-R Tolerability scale, particu-larly the nausea item, which was the most frequentAE reported. The Tolerability scale covers 64% ofthose AEs related to treatment, with an additional23% related to pain, which, if due to headache,is covered by the Efficacy scale. Therefore, thePPMQ-R covered up to 87% of the AEs reported bymigraine patients.

The PPMQ-R was developed for application inrandomized clinical trials comparing differentmedication treatments for acute migraine head-aches. Findings from this research confirm previousrecommendation for use in clinical trials, where it isrecommended that the Total score is used as theprimary treatment satisfaction end-point because ofits evidence on reliability, validity and responsive-ness (from previous work), and because it coverskey domains of importance to patients (16). Thesubscale scores can then be used to examine reasonsfor any observed differences in PPMQ-R Totalscores, and to provide more insight into treatmenteffects. The PPMQ-R may be used in practice-basedstudies to gain information about satisfaction withdifferent migraine treatments, and is also recom-mended for end-point evaluations in multiattackclinical trials of acute migraine therapy. The singleitem ratings of Overall Satisfaction, Efficacy andSide-effects can be used in practice settings or innaturalistic studies (i.e. large simple trials) to gatherinformation on patient satisfaction with treatment.These single-item measures are not recommendedas the only measures for clinical trials, since theyare less sensitive to change and have less reliabilitythan the multi-item subscale and Total scores.

Several potential limitations should be consid-ered when interpreting the results of this study.First, the patient sample was taken from two clini-cal trials, therefore generalizability to the generalpopulation of migraineurs and to those withchronic headaches may be limited. The sample isrepresentative of those migraineurs participating in

clinical trials on migraine treatment, which is dif-ferent from the general population of migraineurs,where approximately 50% do not consult a physi-cian and only 10% receive triptan therapy (27).Second, study participants were receiving eitherplacebo or sumatriptan/naproxen sodium, limit-ing generalizability across different treatments formigraine. However, previous research in commu-nity samples, which reflects standard treatmentpatterns, supports the psychometric characteristicsof the PPMQ-R (16), and the current findings arecomparable to those from a community setting.Although participants in this study were requiredto have had two to six migraines per month andpreviously used triptans and over-the-counter anal-gesics, there is no reason to believe that thesecharacteristics would introduce any bias in theperceptions of the study participants regardingtheir ratings of treatment satisfaction for studymedication.

In conclusion, the PPMQ-R demonstrated ex-cellent internal consistency reliability and goodconcurrent and construct validity in measuring sat-isfaction with migraine treatment. These findingsare consistent with previous psychometric researchon this measure (16). Evidence of the psychometricproperties of the PPMQ-R is important to supportclaims of treatment benefit for the Food and DrugAdministration (28–30). Since this study was con-ducted only in the USA, research is needed toconfirm these findings with migraine patients inother countries. The PPMQ-R is a useful measurefor evaluating satisfaction with pharmacologicaltherapy among migraine patients, particularly inclinical trials.

Acknowledgements

This study was funded by GlaxoSmithKline. The authorsthank Frederick Derosier, DO for help developing adverseevent categories.

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