Table Of ContentWiklundetal.HealthandQualityofLifeOutcomes2013,11:8
http://www.hqlo.com/content/11/1/8
RESEARCH Open Access
Are treatment benefits in neuropathic pain
reflected in the self assessment of treatment
questionnaire?
Ingela Wiklund1*, Stefan Holmstrom2, Malcolm Stoker2, Kathleen W Wyrwich3 and Mary Devine3
Abstract
Background/objective:The Self Assessment ofTreatment (SAT) questionnaire was developed to reflect key patient
reported outcomes ofNeuropathic Pain (NP) treatments. This study aimed to understand how patients perceived
therelevanceand ease of understanding of thequestions inthe SAT and to recommend modifications based on
patient and clinician interviews.
Methods: Semi-structured interviews were conductedwith clinicians and NPpatientsto provideinformation
regarding treatment attributes and the impact of pain. Patientswere debriefedon theSAT, a 5-item scale
evaluating pain, activitylevel, qualityof life (QoL) and satisfaction withtreatment(recommend treatment and
undergo treatmentagain).The SAT has a recall period reflecting back to thestart of treatment. The qualitative
analysis software ATLAS.ti 5.0was used to analyze patient transcripts.Changes to the SATwere integrated into the
questionnaire for a second round ofdebriefinginterviews.
Results: Three NPcliniciansand 44 patients (20 painfuldiabeticneuropathy,16 HIV-associated neuropathy and 8
post herpetic neuralgia) with a mean age of 60.3 (12.3) years and an even gender distribution were interviewed.
Patient treatment experience included anticonvulsants(73%), antidepressants (34%), opioids (25%), and topical
medications (41%). Pain descriptors and treatment attributes were similar across thethreeNP groups. Pain relief
was judged the most important treatment attribute,followed by ability to undertake activities. Sleep improvement
was another important attribute.Activity limitations and QOL were perceived as toobroad and non-specific, and
were split into 3concepts each (activity limitations was split intoself care, daily and physical activities and QOL was
splitinto sleep, emotions, and social function). A 7-day recall period was introduced. The item stem and response
options were made consistent, and a baseline and follow-upquestionnaires were developed (except for the
satisfaction items) to enable monitoring onset oftreatmentbenefitand change overtime.
Conclusions: The content validity oftherevised SATwas improved by thequalitative research, and NP treatment
benefits are reflected ina more consistent fashion bythe changes. Baseline and follow-upversions make it possible
to perform assessments ofchangeover time.
Keywords: Neuropathic pain, Content validity, Self assessment,Questionnaire
*Correspondence:[email protected]
1UnitedBioSourceCorporation,26-28HammersmithGrove,LondonW67HA,
UK
Fulllistofauthorinformationisavailableattheendofthearticle
©2013Wiklundetal.;licenseeBioMedCentralLtd.ThisisanOpenAccessarticledistributedunderthetermsoftheCreative
CommonsAttributionLicense(http://creativecommons.org/licenses/by/2.0),whichpermitsunrestricteduse,distribution,and
reproductioninanymedium,providedtheoriginalworkisproperlycited.
Wiklundetal.HealthandQualityofLifeOutcomes2013,11:8 Page2of13
http://www.hqlo.com/content/11/1/8
Background regular analgesics, suggesting patients are receiving sub-
Neuropathic pain (NP) is one of the most prevalent pain optimal treatment options [21]. However, recently, the
etiologies [1]. It is a disorder of the peripheral nerves—the European Medicines Agency [22] and the US Food and
motor, sensory and autonomic nerves that connect the Drug Administration [23] approved the use of a high-
™
spinal cord to muscles, skin and internal organs [2,3], and concentration capsaicin topical patch 8% (QUTENZA ).
™
is a complex type of pain which requires a demonstrable Capsaicin, in high concentrations like the QUTENZA
lesionasdefinedbytheupdatedpainterminologyanddefi- patch,isatransientreceptorpotentialvanilloid1(TRPV1)
nitions provided by the International Association for the agonist that is useful in relieving pain. Whilst the
™
Study of Pain (IASP); (http://www.iasp-pain.org/AM/Tem- QUTENZA EU label covers the treatment of peripheral
plate.cfm?Section=Pain_Definitions) [4]. Recently, Treede NP in non-diabetic adults, either alone or in combination
andcolleagues[5]redefinedNPas“painarisingasadirect with other medicinal products for pain, the US label is
consequenceofalesionordiseaseaffectingthesomatosen- licensed for the management of neuropathic pain asso-
sorysystem.”Damagetotheperipheralnervoussystemcan ciatedwithpostherpeticneuralgia[22,23].
occur as a result of several disorders including diabetes, The five-item Self Assessment of Treatment (SAT)
infections such as herpes zoster (shingles) or HIV, trauma, questionnaire was developed internally by Neurogesx for
and autoimmune disorders [1,6]. While NP can occur in use in clinical trials to measure key areas of treatment
any location, it often manifests in the extremities such as benefit (i.e. pain, activities, quality of life and treatment
thehands,feet,orlegs.TheoverallprevalenceofNPvaries satisfaction) recommended by IMMPACT [18]. Since
from between 0.9 % to 8% in a general population [7,8]. psychometric documentation of the SAT was lacking, a
AmongHIVpatientsbetween15%and35%haveNP,whilst post hoc analysis was conducted using trials data to
theprevalenceis15%inpatientswithpainfuldiabeticneu- validate the SAT [24]. Theresultsindicatedthatthethree
ropathyorpostherpeticneuralgia[9]. pain and impact items were reliable and valid, whilst the
The NP symptom experience and the evolution of the satisfaction items performed less well [24]. The SAT has
condition are highly idiosyncratic with individual expe- beenusedasa secondaryend-pointintwotrialsassessing
riencesvaryingwidelybetweenpatients[1,6].The course treatment with Capsaicin in human immunodeficiency
of NP can be episodic and recurrent, slowly progressing virus (HIV)-associated peripheral neuropathy (HIV-PN)
™
over many years, or it can quickly become severe and with beneficial results for QUTENZA cited in the me-
debilitating. Both direct and indirect costs of NP to so- dicalreviewconductedbytheFDA[25],aswellasby[26]
ciety are substantial [10-14]. The consequences to the forthetreatmentofpostherpeticneuralgia[22].
individual patient profoundly impair emotional and The psychometric performance suggested that the
physical functioning with consequences such as move- SAT items could be further improved with additional
ment limitation, an inability to perform major activities patient input to ensure that items are clearly phrased,
of daily living, needing help for personal care, frequent relevant and comprehensive, easy to understand, and
use of health care services, and work productivity losses that the response options and recall period are adequate
[10,11,15,16]. The disease burden is also substantial as to better assess pain related treatment benefits when
shown in a comparison of the world wide burden to used in clinical trials. Therefore, the purpose of this
patients of suffering from NP assessed in a cross na- study was to better understand how well the SAT ques-
tional study [17]. The intensity of the pain as well as the tionnaire reflects what patients perceived as relevant
duration of the pain contributes to the distress asso- aspects of pain treatment and to document patient
ciated withNP. understanding of the individual SAT questions. Addi-
Important outcome domains were identified in a sur- tionally, recommendations were provided on how to
vey of people with pain conducted by the Initiative on modify the instrument to be better suited to assess the
Methods,Measurement,andPainAssessmentinClinical benefits of pain treatment by changing the recall period,
Trials (IMMPACT) [18]. These domains formed the based on the information gained in the semi-structured
basis of the IMMPACT group’s recommendations on a patientinterviews.
core set of outcome domains to be included in eva-
luation of treatment benefits [19]. Whilst pain relief Methods
measures are used to determine whether the patient has Clinicianinterviews
actually benefited from an intervention, and provide Clinicians were interviewed to derive information from
valuable information on how effectively pain is being the clinical perspective on the most relevant neuropathic
managed, patient satisfaction measures capture the per- pain symptoms as well as the benefits and drawbacks of
sonal evaluationoftheintervention provided [20]. neuropathic pain treatments. A total of 3 clinicians with
DespitenewertreatmentmodalitiesNPremainsdifficult expertise in pain therapy, anesthesia intensive care, neu-
to treat. Treatment of NP in the past mainly consisted of rology and endocrinology participated in one-on-one
Wiklundetal.HealthandQualityofLifeOutcomes2013,11:8 Page3of13
http://www.hqlo.com/content/11/1/8
™
telephone interviews. On average, the experts reported QUTENZA treatment. Similarly, efforts to recruit
seeing 20 patients per week with NP. This consultation/ patientsfromtheUSAwithavarietyofsocio-demographic
interview was conducted up-front to ensure that patient backgrounds, as well as varied disease and treatment
interview questions would be appropriately addressed in experiences,wereimplementedtoensureadiversepopula-
thesemi-structuredinterview guide. tion was involved. Protocols were approved by an institu-
tional review board, and patient consent was obtained
Patientinterviews prior to discussion of study related materials. Clinicians
General inclusion criteria applied to all study partici- completed an enrollment and clinical form documenting
pants were as follows: male or female; 18 years of age or eachparticipant’seligibilityandtreatmenthistory.
older; presence of painful diabetic peripheral neuropathy During the semi-structured one-on-one qualitative
(PDPN) or NP due to either post herpetic neuralgia interviews, participants were asked to describe their ex-
(PHN) or painful HIVassociated neuropathy (HIV-AN); perience with NP, their treatment history, and how and
presence of painful symptoms due to neuropathic pain why they value available treatment options. Interviews
with a numerical pain rating score (NPRS) of ≥4 at the included questions and exercises designed to elicit par-
time of screening; on a stable (not as needed, i.e., PRN) ticipant discussion of salient pain treatment attributes
treatment for neuropathic pain for at least the past 3 and levels. Participants were asked to rate the import-
months prior to screening; able to participate in a 90- ance of treatment attributes on a scale from 0 (Not Im-
minute, in-person interview; fluent in English (able to portant) to 5 (Very Important). All interviews were led
read and write); and willing and able to complete by a trained moderator. The interview guide included
informed consent prior to study entry. Specific inclusion both structuredandopen-endedquestion.
criteria for each pain group were as follows: PDPN, a Duringtheinterviews,patientswereaskedtocomplete
diagnosis of painful, distal, symmetrical, sensorimotor the SAT and were then debriefed on each of the ques-
polyneuropathy that is due to diabetes and made by the tions to uncover any issues with the SAT questions. The
primary treating physician or Investigator at least one SAT was revised after the first round of interviews and
year prior to the screening visit; PHN, a diagnosis of additional debriefing interviews were conducted to en-
PHN made by the primary treating physician or Investi- sure all changes were perceived as relevant improve-
gator with at least 6 months of pain since shingles mentstotheSAT.
vesicle crusting; and HIV-AN, prior medical history of
HIV-1 infection and prior diagnosis of HIV-DSP or anti- Measures
retroviral toxic neuropathy documented by the consult- During the qualitative interview, in addition to the
ingneurologistorinvestigator. SAT, participants completed a NPRS, and a brief socio-
Exclusion criteria applied to all participants were as demographic questionnaire with questions regarding
follows: parenteral opioid medication use; active sub- age, gender, ethnicity, employment, education, and co-
stance abuse or history of chronic substance abuse morbidconditions.
within the past year, or prior chronic substance abuse
(including alcoholism); neuropathic pain areas located SelfAssessmentofTreatment(SAT)questionnaire
only on the face, above the hairline of the scalp, and/or The SAT evaluation form included 3 questions with 5-
in proximity to mucous membranes; significant pain of point response options to assess the impact of treatment
an etiology other than one type of neuropathic pain on three areas (pain relief; activity level; and quality of
(PHN, PDPN, or HIV-AN); significant ongoing pain life), and 2 additional items regarding: 1) whether the
from other cause(s) that may interfere with judging patient would undergo the treatment again, and 2) a
neuropathic pain, any implanted medical device (spinal comparison of the study treatment to previous treat-
cord stimulator, intrathecal pump, or peripheral nerve ments for pain. For each question, the subject checked a
stimulator) for the treatment of neuropathic pain; recent boxona5-point scale, where themiddleoption(0)indi-
history of a significant medical-surgical intervention; a cated a neutral response and the lower (−2) and higher
clinically-relevant medical or psychiatric condition which, (+2) options indicated a negative or positive response,
in the opinion of the investigator and/or coordinator, respectively. For example, SAT Item 1 asked the patient
would interfere with completing the study including but “How do you assess your pain relief after treatment in
not limited to sensory problems, cognitive impairment, this study?” with the response options of “I feel my pain
acutementalillness,orinadequatelytreateddepressionor is much worse” (−2), “somewhat worse” (−1), “no better
anxiety. and no worse” (0), “somewhat better” (1), and “much
BecausetheSATwasdevelopedforuseintrialsassessing better” (2); Question 2 “How do you assess your activity
the efficacy of the QUTENZA™ patch, efforts were taken level after treatment?”with responsesranging from Ifeel
to recruit a subset of patients who had experience with much less active (−2), I feel somewhat less active (−1), I
Wiklundetal.HealthandQualityofLifeOutcomes2013,11:8 Page4of13
http://www.hqlo.com/content/11/1/8
feel no more and not less active (0), I feel somewhat provide continuing efficacy but the dose titration process
more active (1) to I feel much more active (−2); Ques- canbetimeconsumingandmanypatientsexperienceside
tion 3 “How has your quality of life changed after treat- effectsfrom oral medications. Incontrast, topicalmedica-
ment?” I feel my quality of life is much worse (−2), I feel tionsoffera moreagreeable sideeffect profilebutthedu-
my quality of life is somewhat worse (−1), I feel my qua- ration of efficacy is limited in comparison with the oral
lity of life is no better and no worse (0), I feel my quality medications. Interestingly, the experts suggested that the
™
of life is somewhat better (1), I feel my quality of life is QUTENZA patch may offer an extended duration of
much better (2); Question 4 “Would you undergo this efficacy compared to other topical treatments for NP and
treatment again?” was “administered to subjects with it may be particularly beneficial for patients experiencing
only three response options: “No, absolutely not” (−2), burning superficial pain with allodynia such as those with
“Unsure” (0), and “Yes, definitely” (2) and Question 5 PHN or HIV-AN. Expert opinion also included some
“How do you compare the treatment in this study to negativeaspectsofQUTENZATMsuchaspainfulapplica-
previous medication or therapies for your pain?” The tion, or a lengthy application process requiring assistance
item performance and psychometric properties of the fromamedicalprofessional.
SAThaverecently beenexamined[24].
Patientdemographyandclinicalcharacteristics
TheNumericalPainRatingScale(NPRS) A total of 44 patients participated in the one-on-one
The NPRS is commonly used in pain medication trials qualitative interviews in California, Florida, Georgia, and
[27] and is one of the many pain items in the modi- Virginia over a 3-month period. Twenty patients suf-
fied Brief Pain Inventory (BPI) [28,29]. The NPRS is fered from PDPN, 16 had HIV-AN and eight had PHN.
an 11-point graded scale ranging from 0–10 with 0 Demographic and clinical characteristics of the partici-
depicting “no pain at all” and 10 denoting “worst pain pantsareprovidedinTable1andTable2,respectively.
imaginable.”
Patientexperienceswithneuropathicpain
Dataanalysis Participants reported experiencing many different types
Descriptive statistics (mean, standard deviation and fre- of pain and pain symptoms. The most prevalent pain
quency) were used to characterize the interview sample descriptions included: burning, mentioned by 30%
in terms of sociodemographic data, health status, the (n=13) of the participants, numb (n=12. 27%), sharp
numerical pain rating and clinical characteristics. All (n=10, 23%), pins and needles (n=9, 21%) and throbbing
interviews were audio recorded with the participant’s pain n=6, (14%). Less frequent pain descriptors charac-
permission and transcribed for analysis. The qualitative terized the pain as hot, stabbing, tingling, aching, dull,
analysis was conducted by coding the transcripts using heavy, and shooting pain, whilst only one or two partici-
ATLAS.tiversion 5.0[30]softwaretoorganize the coded pants described the pain as cramping, electrical shock,
concepts using a coding dictionary developed by the freezing/cold, hypersensitive, biting, clamping, cutting,
coding staff as the coding process continued and con- piercing, pinching, pressure, and tight. There was no
cepts were identified. This process was adhered to sys- major difference between the NP populations in the way
tematically analyze, code, and compare quotes from they described theirpain(Table 3).
participantinterviewsinordertoevaluatetheunderlying These pain symptoms had an impact on daily activities
structureofthequalitativedata. (Table 4) and aspects of participants’ personal lives. The
The information gained in the interviews was used to most common impact of NP on daily activities reported
explore any potential relevant missing items and to pro- by participants across all pain groups was that pain
vide recommendations on how to modify the SAT for affected the ability to “do” or engage in daily activities,
useinfuturestudies. which was reported by 61% (n=27) of the participants
with no difference across NP populations. Participants
Results commonly reported that neuropathic pain interrupted
Clinicalexpertinputonneuropathicpain daily activities and that they avoid doing certain acti-
According to the clinical experts, there is a high degree vities asaresult oftheirneuropathic pain.
of variability in descriptions of NP experiences among Participants were asked to provide examples of the ac-
patients with the same type of NP but the descriptions tivities affected by neuropathic pain (Table 4). Specific
do not differ significantly across types of NP. Experts daily activities that were adversely affected by neuro-
indicated that patients often report challenges with pain pathic pain included: shopping, work, cooking, driving
relief and there is a low efficacy rate with the existing NP or transportation, cleaning, and wearing clothing. Daily
treatments. Common oral medications prescribed for NP, activities identified by 1 or 2 participants included: ca-
such as anticonvulsants, opioids, and antidepressants ring for someone else, going to appointments, home
Wiklundetal.HealthandQualityofLifeOutcomes2013,11:8 Page5of13
http://www.hqlo.com/content/11/1/8
Table1DemographiccharacteristicsandselfreportCo Table2Clinicalcharacteristics
Morbidconditions TotalN=44
TotalN=44 MeanofPatients’OnsetofNeuropathicPain 7.5(8.1)[1.0-40.0]
MeanAge,Years(SD)[Range] 60.3(12.3)[30.0-80.0] DiagnosisinYears(SD)[Range]
Gender(n,%) TypeofNeuropathicPain(n,%)
Female 23(52.3%) PostherpeticNeuralgia(PHN) 8(18.2%)
Male 21(47.8%) HIV-associatedNeuropathy(HIV-AN) 16(36.4%)
Ethnicity(n,%) PainfulDiabeticPeripheralNeuropathy(PDPN) 20(45.5%)
NotHispanicorLatino 38(90.5%) MeanofPatient’sRatingofPain(SD)[Range] 6.9(1.7)[3.0-10.0]
HispanicorLatino 4(9.5%) FrequencyofOpioidMedication1
Race(n,%)1 Hydrocodone 5(11.4%)
White 31(70.5%) Oxycodone 1(2.3%)
BlackorAfricanAmerican 10(22.7%) Other2 9(20.5%)
Other2 3(6.8%) FrequencyofNon-OpioidMedication1
EmploymentStatus(n,%)1
Pregabalin 13(29.6%)
Retired 18(40.9%)
Duloxetine 7(15.9%)
Disabled 14(31.8%)
Gabapentin 27(61.4%)
Part-time 5(11.4%)
Other3 24(54.5%)
Full-time 3(6.8%)
FrequencyofTopicalMedication1
Unemployed 4(9.1%)
QUTENZATM 11(25.0%)
Homemaker 1(2.3%)
Lidocaine 3(6.8%)
Other3 1(2.3%)
Other4 2(4.6%)
NeuropathicPain(n,%)
MeanPatientHeight,feet(SD)[Range] 5.5(0.4)[4.5-6.2]
Mild 4(9.3%)
MeanPatientWeight,pounds(SD)[Range] 196.7(45.9)
Moderate 20(46.5%)
[108.0-315.0]
Severe 11(25.6%)
1Thesecategoriesarenotmutuallyexclusive.
VerySevere 8(18.6%) 2OtherOpioidmedicationsreportedbyparticipantsincluded:Darvocet(n=1);
MSContin(n=1);Tramadol(n=6);Vicodin(n=1).
HealthConditions(n,%)1 3OtherNon-Opioidmedicationsreportedincluded:Advil(n=2);Aleve(n=1);
Anxiety 7(15.9%) Amitriptyline(n=3);Aspirin(n=2);Baclofen(n=1);Carbamalbpine(n=1);
Celebrex(n=1);Cymbalta(n=1);Diclofenac(n=1);Glipizide(n=1);Motrin(n=1);
Arthritis 16(36.4%) Naproxen(n=2);Nortriptyline(n=1);Topamax(n=3);Tylenol(n=1);Tylenol
ExtraStrength(n=2).
Asthma 7(15.9%)
4OtherTopicalmedicationsreportedbyparticipantsincluded:Amitriptyline
Cancer 2(4.6%) 5%,Gabapentin5%,Ketamine8%(n=1);Zotrix0.75Cream(n=1).
COPD 11(25.0%)
Depression 13(29.6%) maintenance, running errands, and hygiene. The impact
Diabetes 18(40.9%) of neuropathic pain on daily activities was similar across
Hepatitis 2(4.6%) pain types. During these discussions, sleep disturbance
HTN 17(38.6%) was commonly identified and had a negative impact
among20participants(46%) acrosspaintypes.
Insomnia 4(9.1%)
The physical activities affected by neuropathic pain
BackPain 15(34.1%)
variedbyNPpopulationtype.Fortyfivepercentofparti-
Retinopathy 2(4.6%)
cipants with PDPN (n=9) and 56% of participants with
Stroke 1(2.3%)
HIV-AN (n=9) identified walking and 10% (n=2) and
Other4 11(25.0%) 19% (n=3) respectively identified standing, as physical
None 8(18.2%) activities commonly affected by NP, while none of the
1Participantswerepermittedtoselectmorethanoneresponse. participants with PHN reported difficulty with these ac-
2Otherracialbackgroundsreportedbyparticipantsincluded:EuropeanMix tivities (Table 4). Gardening and yard work were report-
(n=1);Mestizo(n=1).
3Otheremploymentreportedbyparticipantsincluded:Notspecified(n=1). edly affected by PHN (25% of participants, n=2) and
4Otherhealthconditionsreportedbyparticipantsincluded:AIDS(n=2);CHF, PDPN (10% of participants, n=2) but not at all by HIV-
Adema,Neuropathy,RightShoulderTorn(n=1);Emphysema(n=1);Heart
AN participants. Exercise was only discussed as an
attacks(n=1);HeartDisease(CAD),RLS(n=1);Highcholesterol,indigestion
(n=1);HIV(n=1);HIV,Gout(n=1);Migraines(n=1);Neuropathy(n=1). affected physical activity by HIV-AN participants (n=5,
Wiklundetal.HealthandQualityofLifeOutcomes2013,11:8 Page6of13
http://www.hqlo.com/content/11/1/8
Table3Paindescriptions
Pain Illustrativequotation PHN PDPN HIV-AN All
description
(n=8) (n=20) (n=16) (N=44)
02-102-1-0:It'salwayslikeburning,Idon'tknow 4 7 2 13
howelsetosay,butitfeelslikeevenclothestouching,
(50%) (35%) (12%) (30%)
Burning it'sburning.Apparentlyit'snot,butthat'swhatitfeelslike.
04-105-1-0:Whenitgetsreallybadanditwillburn.Feel
likeitshotburning.
05-102-3-0:It’satinglingahinyourfeetanditgoesupto 0 8 4 12
yourumankleandthenit’slikenumbnesslikeyoudon’tfeel
(0%) (40%) (25%) (27%)
Numb nothing.Youcanbewalkingwithflip-flapsandthenextdayyou
knowyouthinkyoustillhaveyourshoeson,andyou’rewalking
outinyourbarefeet.
01-102-2-0:Itjustcomeson,Imeanit’slikeasharppainand 1 3 6 10
thenitjust-Iusuallyjusttrytowalkitofforrubitoffandthen
(13%) (15%) (38%) (23%)
itgoesaway-andthenitreturns.
Sharp
03-106-2-0:Uh,[clearingthroat]it's-it'slikewhenit'sverysevere
it'slikeI'm-I'mwalkingonabedofnailsorthumbtacksand
it,uh,justtinglingandvery,very,uh,verypainful,sharp,sharppain.
01-101-2-0:Notsomuchpainasitwaspinsandneedles 1 6 2 9
andlittlestabbingandnumbness.
(13%) (30%) (13%) (21%)
PinsandNeedles 03-103-2-0:Apinprick--youknow,lotsofpins,pokingpins
kindofafeelingkindofthing,soit'shardpaintodescribe,
butthat'sascloseasIcanget.
08-104-3-1:Ithinkthefactthatit'swhenitstartsitis-itwill 0 2 4 6
Throbbing kindofthrobandthrobandthrobforawhile.
(0%) (10%) (25%) (14%)
31%). Playing sports, (PHN n=2, 25%; PDPN n=5, 25%; werenotdifferentacrosstheNPpopulations.Thissimilar-
HIV-AN n=3, 19%) and sitting (PHN n=2, 25%; PDPN ityacrosspaintypesisconsistentwiththeobservationsof
n=1, 5.0%; HIV-AN n=3, 19%) were affected for partici- high intra-pain type variability reported during clinician
pants in all pain groups, with 23% (n=10) of the partici- interviews.
pants identifying playing sports as a problem and 14%
(n=6) of the participants identifying sitting as a problem. Treatmentexperiences
Other physical activities, mentioned by only 1or 2parti- Patients were asked to discuss their experience with NP
cipants, included lifting and playing with kids. Partici- treatments. The most commonly reported type of treat-
pants in all pain groups reported an impact on social ment was anticonvulsant medication followed by antide-
activities, but this impact was reported less frequently by pressants (Table 5). Participants also reported treatment
participants with HIV-AN than by participants with with opioid and non-opioid analgesics such as NSAIDs
PHNorPDPN. and acetaminophen. Experiences with pain treatments
Inadditiontotheimpactonactivities,participantsdis- other than oral medications included topical treatments
™
cussed the impacts of NP on their personal lives. About (excluding QUTENZA ). Experience with topical treat-
™
27% (n=12) of participants across all pain groups noted a ments and the QUTENZA patch were more common
negative impact of NP on relationships quoting expe- among participants with PHN (n=5, 63% and n=2, 25%)
riences such as “if you go somewhere with a friend or whilst in HIV-AN 44% (n=7) used the QUTENZA™
somethingandthenyouhavetobe-I’llbelikesittingthere patch in contrast to only 10% (n=2) and 5% (n=1) in
andthenhavethesharppainsandthenthey’relikeoh,my PDPN patients. Physical therapy, acupuncture and injec-
gosh, what’s wrong with you? You know, it does interfere tions were treatment options only reported by single in-
with your relationships.” Similarly, about 25% (n=11) of dividualpatients.
participants mentioned that pain had a negative effect on During the discussion of current and prior treatments,
their emotional well-being. Only one or two participants participants were specifically asked to share their expe-
reportedexperiencingchangesinmentalstate,outlookon riences with treatment use, availability, cost, and side
life, sex life, feeling short tempered and difficulty concen- effects. It is important to note that some participants
trating/focusingasaresultofneuropathicpain. have tried several different medications within a treat-
Although descriptions of pain experiences and impacts ment type and reported different experiences for the dif-
were highly variable, the experiences reported by patients ferent medications.
Wiklundetal.HealthandQualityofLifeOutcomes2013,11:8 Page7of13
http://www.hqlo.com/content/11/1/8
Table4Impactofneuropathicpain
Impactondaily PHN PDPN HIV-AN All
activities Illustrativequotation
(n=8) (n=20) (n=16) (N=44)
Affectsabilitytodoactivities 01-104-2-0:Imeanit-it-it’sbad.Ithurts,uh,sobadthat,you 4 12 11 27
know,sometimesIcan’tgetup.Ican’twalk....Youcan’tdo
(50%) (60%) (69%) (61%)
anything.And,youknow,youdowhateverandyoujustsit
thereanddonothing.
03-102-2-0:WhenI-whenIgointo,um-whenI-whenmy
painstarts,yeah,absolutely,Ican'tdoanything.Ican'tthink.
05-104-30:Um,becauseIcan'treallydothethingsthat
Ireallywanttodo.
05-105-3-0:Well,be-itbothersmebecauseIcan'tgetthis
stuffdoneIneedtogetdone...AndIcouldn'tcookforthe
children,Ididn'tgotothegrocerystore,sothere'snothing
reallythereforthemtomakewhenI'mnotabletofixthem
somethingtheirselves.Sothatreallybothersmebecause
thenIreallygottoget
upand,uh,itreallyhurts.YouknowwhatI'msaying,
Igottogetup.
InterruptsActivities 01-102-2-0:IfI’mtryingtodosomethinganditcomeson, 2 5 1 8
itinterruptswhatI’mdoingandthen,ofcourse,Ihaveto
stopandwait‘tilitquitshurtingandthencontinuewith (25%) (25%) (6%) (18%)
whateverIwasdoing.So,consequently,Idon’tdonearall
thethingsthatIusedtodo.
02-101-1-0:Itreallydoesn'taffectanything,Ijusthavetostop
certainthingsafteracertaintime.
04-104-2-0:Well,itstopsmefromdoingalotof,uh,walking
anddoingthingsthatI'mdoing,Ihavetostop.
Avoiddoingactivities 03-103-2-0:Itrynottowalkmuch,Ialwaystrytofindaway 1 4 2 7
tositdownwhereit'sbesttoputmyfeetup.
(13%) (20%) (13%) (16%)
06-101-2-1:Well,if-ifI'mgoinganyplace,youknow,thatIhave
todoanywalkingor-Itendnotto-togoifIcanhelpit,youknow.
08-101-3-1:Well,sociallyandpersonally,itgoesbacktodo-being
abletodothelittlethingsthat-uh,thatcausesmetobeafraid.
When asked to describe how easy or difficult it was to using topical treatments indicated that the treatments
use each treatment, most participants (n=75, 82%) were easy to use. Half (n=5) of the participants that had
describedtreatmentsaseasytouse.Anticonvulsantmedi- triedtheQUTENZATMpatchsaidthatitwaseasytouse.
cations weregenerallyreported as easy to use by between Duringthediscussionoftreatmentuse,participantsspe-
73%–88% of participants across all pain groups, as were cifiedboth positiveand negativeaspectsof treatment that
opioids (65–100%) and non-opioid analgesics (57%– influenced their opinions on treatment usability. Pain
100%). Most participants (78%–100%) with experience relief, low pill burden, and ease of taking a pill were
Table5Currentandpriorneuropathicpaintreatments
#of #of Anticonvulsantor Antidepressant Opioid Non-OpioidAnalgesic Topical Qutenza
participants treatments anti-seizuremedications medications medications medications treatments patch
Total 95 32 15 11 14 8 10
N=44 (73%) (34%) (25%) (32%) (18%) (23%)
PHN 23 5 3 4 1 5 2
N=8 (63%) (38%) (50%) (13%) (63%) (25%)
PDPN 42 16 9 5 7 2 11
N=20 (80%) (45%) (25%) (35%) (10%) (5%)
HIV-AN 30 11 3 3 6 1 7
N=16 (69%) (19%) (19%) (38%) (6%) (44%)
1OnePDPNparticipantwasprevioustreatedwithQutenzabutdidnotrecallthetreatment.Therefore,thisparticipantwasnotaskedaboutthetreatment
experience.
Wiklundetal.HealthandQualityofLifeOutcomes2013,11:8 Page8of13
http://www.hqlo.com/content/11/1/8
highlightedaspositivebenefitsbyamajorityofthepartici- Factorsfortreatmentsuccess
pants.Otherparticipantsmentioneddurationofrelief,im- Characteristics of ideal treatments could be separated
provement in sleep, ability to take the treatment with into 3 categories: results of treatment (n=40), route of
other medications, onset of relief, cost, and side effects. administration (n=33), and treatment use (n=19). Ideal
Twelve out of 16 participants (75%) with HIV-AN treatment attributes described by participants were ge-
reportedthatpainreliefwasimportantintheirassessment nerally similar across pain groups and focused on
oftreatmentusability.Therewerefewproblemsassociated complete elimination of pain, permanent pain relief and
with oral medications although 4 participants (13%) com- no side effects. As to most favored routes of administra-
mented on the high pill burden associated with anticon- tion, taking a pill, use of a patch, and topical administra-
vulsants. Morethan half of the participants (n=25, 57.7%) tion werereportedinthatorder.
reported changing neuropathic pain treatments at least
onceduringthecourseoftheirtreatmentexperience.The
PatientfeedbackontheSAT
main reasons for switching were ineffective treatments
During the debriefing interviews, several issues were
(n=13,50%) and side effects (n=11,42.3%). Other reasons
reported related to the SAT. In question 1, the question
for discontinuing a previous therapy included: physician’s
stem and the response options presented challenges
decision, insufficient pain relief, contraindication with
since they were not consistent, e.g., the question asks for
anothermedication,highcost,highpillburden,toomuch
an assessment of the pain level and the response option
trouble to use, short duration of effectiveness, medication
states the pain is worse/better after treatment. Question
takenoffthemarket,messyapplication,andlossofeffect-
2 asks respondents to assess the activity level after treat-
iveness. The most common reason for starting a new
ment. Participants found “activity level” to be too broad
medication was to provide additional pain relief (n=6,
and unspecific and provided specific examples on acti-
23%).Participantsalsoindicatedthatnewmediationswere
vities affected by pain. Question 3 asks about changes in
addedtoon-goingtreatmentstohelpwithsleeping,break
quality of life after treatment which generally was con-
throughpain,orseverepain.
sidered to be an unspecific concept. Similar to the ques-
Intheratingoftreatmentattributes,painrelief(identi-
tion on activity levels, patients reported items they
fied by 47% of the participants, n=45) was identified as
found were important to their quality of life. In question
the key aspect of treatment. By treatment, pain relief
4whererespondentsare asked to state ifthey would like
was named as the best aspect of treatment with the
™ to undergo treatment again it became obvious that the
highest frequency for opioids (n=4, 64%), QUTENZA
responseoptions did not fit the questionsstem and were
(n=4, 60%), and anticonvulsants (n=11, 50%). Other
not consistent with responses to the questions. Question
characteristics identified as “best aspects of treatment”
5 asks respondents to compare the treatment to other
included ease of use, no side effects, availability, cost,
pain treatments with responses describing level of pre-
help with sleeping, duration of effectiveness, and quick
ference for previous or current treatment. Hence the
on-set. “Reduction in pain” was rated as the most im-
question stem and the response options did not match
portant attribute across all pain groups with an average
which caused problems fortherespondents.
score for all of = 4.7 (range 0–5). Among PHN patients
Additionally,therecallperiodforallitemsisretrospect-
the average was 5.0, PDPN4.6, and HIV-AN=4.8. Partici-
ive requiring patients to reflect back to when treatment
pantswithPHNandHIV-ANrated‘Durationofpainre-
was started which is difficult to remember precisely and
lief’ as tied with ‘reduction in pain’ as the two most
therefore fraught with recall bias. The use of positive and
important attributes in determining treatment success
negative numbers to depict the response options, espe-
(average scores of 5.0 out of 5 and 4.8, respectively). The
ciallythenegativenumbersalsocausedconfusion.
second highest rated attribute for participants with
PDPN was “improvement in ability to do your usual ac-
tivities”(averagescore=4.5). ModificationsoftheSAT
The most common treatment characteristic, irrespect- The patient input suggested that items 2 (activity level)
ive of mode of administration, identified by participants and 3 (quality of life) were too broad and nonspecific.
as the “worst aspect of treatment” was side effects (28%). Therefore, these questions weresplit into 3 sub-questions
Pill burden was identified as the worst aspect for nine eachusingthedetailedinformationderivedinthequalita-
oral therapies discussed byparticipants. tiveresearch.Thequestionswererevisedtoincludeexam-
Both clinicians and patients commented on topical as ples of specific activities to describe examples of self care
opposedoralmedicationswithtopicalmedicationoffering activities, daily activities and physical activities, all fre-
a more favorable side effect profile. These finding suggest quently mentioned in the interviews. With regards to
that side effects play an important role when it comes to question 3, the same procedure was followed replacing
treatmentsatisfactionanditsevaluationinclinicaltrials. quality of life with specific aspects of your life using
Wiklundetal.HealthandQualityofLifeOutcomes2013,11:8 Page9of13
http://www.hqlo.com/content/11/1/8
emotionalwellbeing, sleep and social functionas illustra- byLeidyandVernon [33]andMagasietal.[34].Specific-
tive examples, these again were derived from the ally, they define saturation as the point at which no sub-
interviews. stantially new information/concepts continue to emerge
Questions 4 and 5 they were rephrased to “Based on beyond what has been previously mentioned when inter-
your experience with the study treatment, would you viewing the last few patients. Additional support can be
like to receive this treatment again?” (no, definitely not– found in the FDA guidance document [35], “The num-
yes, definitely) and “Based on your experience with the ber of patients is not as critical as interview quality and
study treatment, overall how does this treatment com- patient diversity included in the sample in relation to
pare to other treatments you have received in the past?” intended clinical trial population characteristics.” In ge-
(very much worse–very much better). Therecommenda- neral, the 3 NP populations were similar in the way they
tion is to use questions 1–3 at baseline and predefined described pain and the impact of pain symptoms. Clini-
follow up visits, and to include questions 4 and 5 at the cians reported a high variability in terms of pain report-
final visitonly. ing across patients but not across different NP types.
For questions 1–3, the recall period was changed to Although a small number of clinicians were interviewed
“Over the past 7 days.” The response options for ques- for this study, they provided similar input on the va-
tions 1–3 were changed to not at all/slightly better/ riability of pain experiences. The pain descriptors used
moderately better/quite a bit better/very much better by patients also varied, but were consistent irrespective
forall3questionstoimproveconsistency. of NP type and very also similar to the descriptors
Baseline and follow up versions of SAT questions 1–3 included in the McGill short form pain questionnaire
were also developed to enable assessment of response to where pain is referred to as debilitating, burning, sharp,
treatment over time. Given the nature of questions 4 and jabbing, deep, and aching, and can persist for months or
5nobaselinequestionsweredevelopedfortheseitems. years [36,37]. The similarity in pain description across
The changes made to the SAT to address the issues all three NP types indicates that the content of the SAT
identified during patient interviews are summarized in isapplicablefor useacrossthedifferentNPpopulations.
Table6. Similarities supporting the use of the SAT across all
three NP populations prove that the concept of satisfac-
Discussion tion with treatment assessment is fundamental in the
There are a couple of pain satisfaction surveys. The evaluation of pain medication with both the clinical
American Pain Society (APS) Satisfaction Survey is one experts and the patients rating the reduction in pain as
of these and has shown that satisfaction was influenced the most important treatment attribute followed by the
largely by effectiveness of medication, independent of ability to perform usual activities (by the PDPN popula-
pain intensity [31]. This suggests that a satisfaction sur- tion) and duration of pain relief (by the PHN and HIV-
vey related to the effectiveness of a pain medication is ANpopulations).
an important measurement tool for use in clinical trials As pain reduction is unanimously identified as the
of novel pain treatments which is also consistent with most important aspect of treatment, it is not surprising
therecommendationsofthe IMMACTgroup[18]. that changes in pain have been shown to be closely
Even though the APS Satisfaction Survey focused on linkedtoimprovementinqualityoflife[13].Onceagain,
pain management in general practice, it was not directly in the interviews, no difference was seen between the
related to satisfaction with medication. Thesameapplies groups in terms of the impact of NP and the disruption
to another pain survey, the Pain Treatment Satisfaction of ability to perform daily activities and its impact on
Scale (PTSS) [32] which measured satisfaction in patients quality of life. With similarities in terms of pain defini-
receiving treatment for acute or chronic pain; it was not tionsandsimilaritiesintheway thatitaffectsindividuals
designed for use in clinical trials, as it evaluates satisfac- acrossallNPtypesaswellasthefactthatpainreduction
tionwithmedicalcarereceivedaswellaspainmedication. is a critical component of treatment, it appears that the
Although a variety of instruments capturing patient satis- SATwouldbeappropriatefor useinallNPtypes.
faction exists, none of these measures were identified as Pain is one area of research where the subjective ex-
appropriate for assessingpatient satisfaction withmedica- perience and reporting by the patient is well-established
tion used to evaluate the effect of treatment of chronic and the concept of self assessment is particularly rele-
pain in the context of a clinical trial, which led to the vant. The importance of patient report/self assessment
developmentoftheSAT. can be seen in work conducted by Taylor-Stokes and
In all, forty-four patients across three NP populations colleagues [38] where there was significant association
were interviewed which can be regarded as a sufficiently between patient- and physician- rated severity but phy-
large sample size. The consistency of the findings sup- sician and patient ratings were discordant with physi-
port content validity and concept saturation as defined cians underestimating severity in 46.7% of patients who
hW
TIteamble6SumOmrigairnyalofsuggestedrevisioCnhsantgoetsheSAT Revisedbaselineitem Revisedfollowupandlastvisititems ttp://wiklund
Instructions Pleasemarkoneresponsefor Instructionstomarkresponses Instructions:Pleasemarkyourresponsebymarking Instructions:Pleasemarkyourresponsebymarking ww et
eachquestion clarified. oneoftheboxesforeachquestionbelow. oneoftheboxesforeachquestionbelow. .hq al.
Item1 Howdoyouassessyourpain 1.Itemdevelopedtoassesspainlevel 1.Overthepast7days,howwouldyourateyourpain 1.Overthepast7days,howmuchhasthestudy lo.c Hea
levelaftertreatmentinthis atbaseline level? treatmentimprovedyourpainlevel? om lth
study? /con and
-Ifeelmypainismuchworse 2.Recallperiodchangedto7days -Nopainatall -Notatall te Q
(-w−Io2fr)eseel(m−1y)painissomewhat 3co.Tnhsiestreenstpwonitshetohpetiiotenmswsteermemanadde -Mildpain -Slightlybetter nt/11/1/8 ualityofL
withotherresponseoptionsonthe ife
questionnaire O
u
tc
-Ifeelmypainisnobetter 4.Weightingnumberswereremoved -Moderatepain -Moderatelybetter o
m
andnoworse(0) e
s
2
-Ifeelmypainissomewhat -Severepain -Quiteabitbetter 0
1
better(1) 3
,
1
-Ifeelmypainismuchbetter -Veryseverepain -Verymuchbetter 1:8
(2)
Item2 Howdoyouassessyour 1.Itemdevelopedtoassessactivityat 2.Overthepast7days,howmuchhaspainaffected 2.Overthepast7days,howhasthestudytreatment
activitylevelaftertreatmentin baseline. yourabilitytodothefollowingactivities: improvedyourabilitytodothefollowingactivities:
thisstudy?
-Ifeelmuchlessactive(−2) 2.Recallperiodchangedto7days A.Dailyselfcareactivities,suchasshoweringand A.Dailyselfcareactivities,suchasshoweringand
dressing? dressing?
-Ifeelsomewhatlessactive 3.Theitemwassplitintoseveral B.Dailyactivities,suchascleaning,fixingthings B.Dailyactivities,suchascleaning,fixingthings
(−1) questionsthataremoretargetedto aroundthehouse,groceryshopping,preparingmeals, aroundthehouse,groceryshopping,preparingmeals,
painreliefaspectsnotedduringthe goingtoappointments,caringforsomeoneelseand goingtoappointments,caringforsomeoneelseand
qualitativeinterviews otherdaytodaytasks? otherdaytodaytasks?
-Ifeelnomoreandnotless 4.Theresponseoptionsweremade C.Physicalactivities,suchaswalking,exercising, C.Physicalactivities,suchaswalking,exercising,
active(0) consistentwiththeitemstemand gardeningoryardwork? gardeningoryardwork?
withotherresponseoptionsonthe
questionnaire
-Ifeelsomewhatmoreactive 5.Weightingnumberswereremoved ResponseoptionsforA,B,andC ResponseoptionsforA,B,andC
(1)
-Ifeelmuchmoreactive(−2) -Notatall -Notatall
-Slightly -Slightlybetter
-Moderately -Moderatelybetter
-Quiteabit -Quiteabitbetter
-Verymuch= -Verymuchbetter P
a
g
Item3 Howhasyourqualityoflife 1.Itemdevelopedtoassessqualityof 3.Overthepast7days,howmuchhaspainaffected 3.Overthepast7days,howmuchhasthestudy e
1
changedaftertreatmentin lifeatbaseline. thefollowingaspectsofyourlife: treatmentimprovedthefollowingaspectsofyourlife: 0
thisstudy? of
1
3
