ORIGINAL RESEARCH

The Better Understanding and Recognitionof the Disconnects, Experiences, and Needs of Patientswith Chronic Idiopathic Constipation (BURDEN-CIC)Study: Results of an Online Questionnaire

Lucinda A. Harris . John Horn . Michele Kissous-Hunt . Leslie Magnus .

Eamonn M. M. Quigley

Received: July 21, 2017 / Published online: November 6, 2017� The Author(s) 2017. This article is an open access publication

ABSTRACT

Introduction: There is limited literature com-paring the experiences and attitudes of patientswith chronic idiopathic constipation (CIC) tothose of healthcare professionals (HCPs) treatingCIC patients. The BURDEN-CIC study was con-ducted to better understand the experiences andongoing needs of CIC patients and to assess theiralignment versus disconnection with the percep-tions and needs of HCPs who treat CIC patients.Methods: The BURDEN-CIC study was anauthor-developed, online questionnaire thatused KnowledgePanel� to survey individualswith CIC (n = 1223). HCPs who treat CICpatients were recruited separately and

participated in a complementary online ques-tionnaire (n = 331).Results: Most patients had used (58%) or wereusing (51%) over-the-counter treatments for theirCIC, with only 16% currently on prescriptiontherapy. More than half (59%) of current CIC pre-scription users were not satisfied/completely satis-fied with their current chronic treatment. Manypatients (42%) felt frustrated regarding their CIC,and a similar percentage (40%) expressed accep-tance that CIC was part of their daily life. Themajority of HCPs agreed that CIC patients werefrustrated (72%), stressed (50%), or fed up (43%)with current treatment options but were relativelyunaware (21%) that patients were accepting oftheir CIC.HCPs reported the greatest challenges intreating CIC patients as response rates to currenttherapies (55%), treatment adherence (55%),management of treatment-related diarrhea (34%),and lack of treatment options (34%).Conclusion: BURDEN-CIC identified that manypatients and HCPs are frustrated and not satis-fied with current CIC treatments due to lack ofefficacy and side effects, such as diarrhea. Thesurvey identified that many patients are ‘‘ac-cepting’’ of their disease, potentially compro-mising treatment outcomes. More dialogue isneeded between HCPs and CIC patients, espe-cially regarding management of treatmentexpectations and side effects. Further, addi-tional treatment options would be useful forboth patients and HCPs.Funding: Synergy Pharmaceuticals Inc.

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L. A. HarrisMayo Clinic, Scottsdale, AZ, USA

J. HornUniversity of Washington, Seattle, WA, USA

M. Kissous-HuntMount Sinai GI, New York, NY, USA

L. MagnusSynergy Pharmaceuticals Inc, New York, NY, USA

E. M. M. Quigley (&)Houston Methodist Hospital, Houston, TX, USAe-mail: equigley@houstonmethodist.org

Adv Ther (2017) 34:2661–2673

DOI 10.1007/s12325-017-0633-5

Keywords: Chronic idiopathic constipation;Functional constipation; Gastroenterology;Quality of life; Survey

INTRODUCTION

Chronic idiopathic constipation (CIC) is acommon functional gastrointestinal disorderwhose prevalence ranges from 2% to 27%among adults, averaging 14% in the UnitedStates (US), and this percentage rises withincreasing age [1, 2]. Chronic constipation hasbeen traditionally defined by the frequency ofbowel movements. Guidelines set forth byRome IV diagnostic criteria base the diagnosison patient-reported symptoms such as strain-ing, lumpy/hard stool consistency, and thesensation of incomplete bowel movements [3].Rome IV criteria also identify that CIC can beaccompanied by the presence of abdominalsymptoms such as bloating and discomfort [3].Additionally, many patients report that CICadversely affects their quality of life andincreases overall healthcare costs [4, 5].

The current treatment goal is to provide mul-ti-symptom relief. The treatment of constipationtraditionally begins with increased dietary fiberand supplementation with bulking agents, exer-cise, and bowel habit training [3]; however, oftenonly partial relief is obtained, and many patientsuse laxatives on a regular basis without medicalsupervision [6]. Laxatives available over thecounter (OTC) are generally recommended forepisodic and not chronic use [7, 8]. If the responseto OTC medications is deemed inadequate thenprescription pharmacotherapies are the next lineof treatment. At the time this study was con-ducted, MiraLAX�, lactulose, linaclotide (Lin-zess�), and lubiprostone (Amitiza�)were availablefor prescription treatment of CIC.

A number of patient-based surveys havereported that patients remain concerned anddissatisfied with traditional, OTC, and thenavailable prescription laxatives [e.g., poly-ethylene glycol 3350 (PEG; MiraLAX�), lactu-lose] for CIC, leaving an unmet need to beaddressed by new and differentiated treatmentoptions [4, 9, 10]. There is, however, limited

published literature comparing the experiencesand attitudes of patients with CIC to theunderstandings and perceptions of healthcareprofessionals (HCPs) who treat CIC patients.The better understanding and recognition ofthe disconnects, experiences, and needs ofpatients with chronic idiopathic constipation(BURDEN-CIC) study was designed to betterunderstand the management pathway, overallsatisfaction with care, impact on quality of life,and unmet treatment needs for patients withCIC, from the perspectives of both patients andthe HCPs who treat CIC patients.

METHODS

Patient Questionnaire

The questionnaire for the BURDEN-CIC studywas developed by all the authors, with thepatient protocol and associated materialsreviewed and approved by the Western Institu-tional Review Board. The BURDEN-CIC studyutilized a proprietary consumer panel (Knowl-edgePanel�) in conjunction with an additionalopt-in panel to identify individuals sufferingwith CIC. KnowledgePanel� is a representativesample of the total US population that accountsfor demographic and epidemiological factors,including age, race, marital status, education,employment status, and geographic region.Recruitment and surveying were conductedbetween June 29, 2016, and January 30, 2017.The questionnaire was self-administered overthe Internet and potential participants weretold only that they were answering a question-naire about their health when initially beingscreened for participation. Eligible panelistsreceived notification of their assigned ques-tionnaires through a password-protected e-mailaccount. All questionnaire responses were con-fidential, with any identifying informationremoved. Participants had the option to leavethe survey at any time, and any incompletestudy data were removed from the overalldatabase. Demographic and geographic distri-butions from the Current Population Surveywere used as benchmarks [11].

2662 Adv Ther (2017) 34:2661–2673

Inclusion and Exclusion CriteriaPanel members who agreed to participate in thestudy were asked to complete an online,self-administered, six-question screener toevaluate whether they met entry criteria.Respondents were eligible to participate in theBURDEN-CIC study if they were proficient inthe English language, were aged C 18 years, hadbeen diagnosed with CIC or fulfilled Rome IVcriteria for CIC, had not been previously diag-nosed as having irritable bowel syndrome withconstipation (IBS-C), and had not been previ-ously diagnosed as having any disease oforganic cause with associated constipation (e.g.,gastrointestinal, neurological). Thus, there weretwo groups of CIC respondents: one with par-ticipants who had a formal diagnosis of CICfrom an HCP and another with participantswho were undiagnosed but who fulfilled RomeIV criteria for CIC from the screener.

Potential participants were not eligible totake the BURDEN-CIC patient questionnaire ifthey were currently pregnant or had beenpregnant in the past 12 months. Respondentswere specifically asked whether they had beendiagnosed by an HCP as having cancer, anorganic gastrointestinal disease (e.g., divertic-ulitis, diverticulosis, inflammatory bowel dis-ease), IBS-C, or spastic or irritable colon.Participants who reported abdominal pain—thehallmark symptom of IBS-C—were not excludedfrom the BURDEN-CIC study unless they indi-cated having been diagnosed with IBS-C.Respondents who had never been diagnosedwith IBS-C but met Rome IV IBS-C criteria asdetermined from the screener, and those whohad been taking opioids or any treatments notapproved by the US Food and Drug Adminis-tration for CIC at the time of the study, werealso excluded.

Questionnaire AdministrationParticipants were required to read and under-stand an informed consent document and werethen given the option to continue with theonline questionnaire. If any panelist did notprovide informed consent, they were not able toparticipate. Panelists who met the inclusioncriteria completed an online, self-administeredquestionnaire that was estimated to take 45 min

to complete. Panelists were advised that theirparticipation was voluntary and that they hadthe option of not answering specific questions.As part of the online study, participants wereasked to report the symptomatology of theirCIC, the impact of constipation symptoms onactivities of daily living, effects and side effectsof CIC treatments, and treatment satisfaction.Question and answer formats includeddichotomous, multiple-choice, and open-ended, as well as numeric rating scales (1–5 or1–7). Data were internally validated to ensurethat patients completed the questionnaire onlyonce, that sufficient time was spent completingthe questionnaire, and that there was a consis-tent response pattern.

Healthcare Professional Questionnaire

For the HCP questionnaire, healthcare pre-scribers who actively treat patients with CICwere recruited to participate in a 45-min onlinequestionnaire based on the IRB-approvedPatient Questionnaire, which was fielded fromJuly 20 to August 10, 2016. The questionnairewas targeted to a random national sample ofgastroenterologists (GEs), primary care physi-cians (PCPs), nurse practitioners (NPs), andphysician assistants (PAs). To be eligible toparticipate, an HCP must have been activelymanaging patients with CIC, seeing at least 50total patients and at least 15 CIC patients permonth. No geographical or workplace settingcriteria were implemented. HCPs were recruitedindependently of participants in the PatientQuestionnaire and were remunerated for theirparticipation in the study. Question and answerformats included dichotomous, multi-ple-choice, and open-ended, as well as Likertrating scales (1–5 or 1–7).

Ethical and Legal Aspects

The patient protocol and associated materialswere reviewed and approved by the WesternInstitutional Review Board. Both the patientand HCP questionnaires were conducted by GfKaccording to the globally accepted standards ofgood clinical practice (as defined in the

Adv Ther (2017) 34:2661–2673 2663

International Conference on Harmonisation E6Guideline for Good Clinical Practice), in accor-dance with the Health Insurance Portability andAccountability Act, and in keeping with localregulations. Informed consent was obtainedfrom all respondents for being included in thestudy.

Statistical Analysis

A standardized statistical analysis approach wasundertaken across both studies with summarystatistics such as mean values, standard devia-tions, minimums, quartiles, and maximums forcontinuous variables and counts and percent-ages for categorical variables. Additional analy-ses were conducted with respondents who werefelt to have factors that would characterizethem as having ‘‘more severe’’ CIC. Theserespondents had C 1 of the following:• Productivity impacted by CIC symptoms

(defined as C 1 day in a typical month whereCIC symptoms interfered with productivity),or

• Personal activity impacted by CIC symptoms(defined as C 1 day in a typical month whereCIC symptoms interfered with personalactivity), or

• An emergency room (ER) visit for CIC-re-lated symptoms (defined as C 1 visit in thepast year), or

• A current prescription treatment for CIC(defined as C 1 prescription for linaclotide,lubiprostone, PEG, senna, or lactulose/kristalose).

RESULTS

There were 29,665 clicks on the Patient Ques-tionnaire link, with 27,709 panelists complet-ing the screening test. A total of 1223respondents qualified for and completed thequestionnaire. The majority of respondentswere female (69%), Caucasian (non-Hispanic;65%), and married (55%), with a mean age of49.1 years (Table 1). Patients had suffered fromsymptoms of CIC for a median of 4 years (meanage at symptom onset, 44.9 years).

Table 1 CIC patient demographics and baselinecharacteristics

CIC patientsn5 1223

Female 69%

Age, years, mean (SD) 49.1 (18.0)

Age at symptom onset, years, mean (SD) 44.9 (17.7)

Race/ethnicity

White/non-Hispanic 65%

Black/non-Hispanic 13%

Mixed/non-Hispanic 3%

Other/non-Hispanic 3%

Hispanic 16%

Highest education level

High school—no graduation 7%

High school—diploma/GED 27%

College—no graduation 26%

College—graduation 28%

College—post-graduate 12%

Current treatment to manage CIC symptoms

Lifestyle changes

General diet changes 32%

Increased activity and exercise 24%

Meditation/yoga/relaxation techniques 6%

Gluten-free diet 5%

OTC treatment remedies

Fiber 31%

Stool softeners 25%

Probiotics/prebiotics 20%

Non-prescription laxatives 17%

Non-prescription stimulant laxatives 17%

Other 5%

Prescription therapy 16%

OTC over-the-counter

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The online HCP questionnaire was com-pleted by 331 HCPs, including 155 GEs, 76PCPs, 50 NPs, and 50 PAs (Table 2). The major-ity of HCPs were male (63%), had been in clin-ical practice for more than 17 years (mean,17.5 years), and were spending over 95% oftheir time in direct patient care (mean, 97%).

Describing Constipation

A wide variety of emotive terms were used todescribe how patients feel about their CIC andits symptoms (Table 3). From a multiple-choicemenu, respondents most often indicated feelingfrustrated, being accepting of constipation aspart of daily life, and feeling stressed. Respon-dents with more severe CIC also reported feel-ing frustrated, stressed, and accepting of CIC;however, they were more likely to report feelingfed up, depressed, and embarrassed and muchless likely to use a positive term such as being incontrol. The majority of HCPs felt that patientswith CIC were frustrated, stressed, and fed upabout their condition, in line with what the

patients themselves reported feeling. HCPs alsoexpressed that they thought their patients wereobsessed with symptoms and were lackinganswers. Only 10% of HCPs thought theirpatients with CIC were in control and only 21%recognized that patients were accepting of CIC,suggesting a disconnection between patientsand HCPs.

Symptoms of CIC

When asked to describe the first symptoms theyexperienced when they began suffering fromCIC (multiple-choice menu), diagnosed andundiagnosed respondents used similar terms,including straining, hard/lumpy/pebble-likestools, and abdominal discomfort (Table 4).Undiagnosed respondents also commonlyidentified infrequent stools as the first constipa-tion-related symptom they experienced andwere much less likely to report abdominalsymptoms among the first symptoms. Themajority of diagnosed and undiagnosedrespondents defined, in an open-ended format,

Table 2 Healthcare professional demographics

GEn5 155

PCPn5 76

NPn5 50

PAn5 50

Male 84% 75% 8% 34%

Age, years, mean (SD) 48.8 (8.2) 50.7 (5.9) 48.6 (7.6) 44.3 (9.0)

Years in clinical practice, mean (SD) 17.3 (7.4) 20.2 (6.1) 15.0 (5.5) 16.2 (7.2)

Time spent in direct patient care, %, mean (SD) 96.5% (5.1%) 97.6% (4.2%) 97.0% (5.6%) 96.4% (5.6%)

Practice setting

Community practice 62% 57% 34% 40%

Solo practice 21% 32% 30% 48%

Hospital-based practice 9% 8% 18% 10%

Academic practice 8% 3% 8% –

Medical specialty

Primary care/general practice – 100% 38% 34%

Gastroenterology 100% – 38% 53%

Internal medicine – – 18% 12%

GE gastroenterologist, NP nurse practitioner, PA physician assistant, PCP primary care physician

Adv Ther (2017) 34:2661–2673 2665

infrequent stools as bowel movements thathappen only once every 3 (37% and 36%,respectively) or 4–5 days (22% and 30%,respectively).

In discussing which of these CIC symptomsfinally resulted in the patient seeking medicalcare (multiple-choice list), diagnosed patientsmore commonly complained of abdominalpain/discomfort (55%) compared with undiag-nosed respondents (17%). Conversely, thesymptoms of difficulty with bowel movement(63%) and straining (42%) led more undiag-nosed respondents to talk to an HCP comparedwith diagnosed patients (52% and 33%,respectively). These data suggest that the pres-ence of abdominal symptoms may be a primarytrigger for patients to finally seek medical careand get diagnosed.

When describing the degree of bothersome-ness of current CIC symptoms (ordinal scale of1–5), patients and HCPs had similar opinions.In the evaluation of the impact of CIC onquality of life, most CIC respondents rated theirsymptoms as bothersome, very bothersome, or ex-tremely bothersome (32%, 21%, and 8%, respec-tively). Likewise, respondents with more severeCIC and HCPs were aligned in the degree of

bothersomeness on quality of life (severe CICpatients, 36%, 29%, and 11%; HCPs, 26%, 60%,and 13%, respectively). Of the total CICrespondent population, the top three mostbothersome symptoms were difficulty withbowel movement (56%), straining (37%), andabdominal pain/discomfort (39%). HCPs werealigned with patients in identifying the mostbothersome symptoms of CIC as difficulty withbowel movement (47%), abdominal bloating/distension (45%), abdominal pain (38%), andabdominal discomfort (35%).

Impact of Constipation on Activitiesof Daily Living

When asked how many days per month theirCIC symptoms interfered with personal activi-ties (e.g., social gatherings, sporting events,family activities, hobbies), 60% of CIC respon-dents were affected on 4 out of 30 days permonth, which equates to nearly 7 weeks peryear. Diagnosed patients experienced an aver-age of 4 days/month with personal activityimpacted, increasing to 7 days/month for thosepatients who reported at least 1 day/monthimpacted (33%). Undiagnosed respondents

Table 3 Common terms used to express how patients with CIC feel about their condition

Emotive terms All CICpatientsn5 1223 (%)

More severe CICpatientsn5 847 (%)

All HCPsn5 331(%)

Frustrated 42 55 72

Accepting: just part of my life 39 33 21

Stressed 28 38 49

Fed up 24 32 43

In control: I use treatments that help me manage my symptoms

well

23 19 10

Embarrassed 18 24 34

Depressed 15 21 34

Lacking answers 14 18 35

Fine: it is not a big deal 14 7 7

Obsessed by symptoms 8 12 42

CIC chronic idiopathic constipation, HCP healthcare professional

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reported an average of 1 day/month with per-sonal activity impacted, increasing to5 days/month when including those with atleast 1 day/month impacted (67%). Patientsalso reported missing time from work andschool: 25% of patients reported that theymissed * 60 days per year, which equates to apotential annualized percentage loss of pro-ductivity of 23%. Diagnosed and undiagnosedrespondents averaged 5 and 3 days/month,respectively, where productivity was impacteddue to CIC. Finally, 14% of patients visited theER with a median occurrence of one visit peryear, which provides an increased burden onhospital and emergency care resources. GEsreported that 16% of CIC patients who areunder their care visited the ER because of theirconstipation symptoms, which is in closealignment with what patients reported.

Treating the Symptoms of CIC

Prior to seeing an HCP, both diagnosed andundiagnosed respondents first turned to diet-ary changes (45% and 37%, respectively),

increased fiber (40% and 42%), and stool soft-eners (37% and 35%) to manage their symp-toms of CIC. Patients also cited using OTClaxatives (24% and 27%) and OTC stimulantlaxatives (24% and 25%). In total, 40% of allCIC patients reported using some form of OTClaxative, using an average of three OTC prod-ucts prior to consulting an HCP. HCPs reportedthat they were aware that most CIC patients trya variety of OTC treatments and lifestylechanges before they seek help from an HCP,and believed that most patients try increasingtheir fiber intake (41%) and taking stool soft-eners (33%). Regarding the initial CIC conver-sation with their HCP, patients reported thattheir HCP recommended general diet changes/home remedies (57%), increasing daily activ-ity/exercise (41%), continuing on current OTClaxative [with (15%) or without (23%) dosagechange], and initiation of a prescription CICtreatment (22%). Only 40% of respondentswere satisfied or completely satisfied with OTClaxatives, with 47% of respondents reportingthat they experienced diarrhea at least some ofthe time.

Table 4 Symptoms first experienced by patients suffering from CIC

Symptoms All CICpatientsn5 1223 (%)

Diagnosedpatientsn 5 1035 (%)

Undiagnosedpatientsn5 188 (%)

Difficulty with bowel movement 82 81 87

Straining 64 60 79

Hard, lumpy, or pebble-like stools 57 55 66

Infrequent stools 53 49 68

Abdominal discomfort 51 55 35

Feeling of incomplete bowel movement, like you did not

‘‘finish’’

49 50 48

Bloating/distension 48 50 38

Stomach cramps 33 36 21

Bleeding (blood on stool, toilet paper, or in toilet bowl) 24 26 20

Rectal pain 21 23 12

Nausea 13 14 10

CIC chronic idiopathic constipation

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In describing their current treatment plan,only 16% of patients indicated that they werecurrently taking a prescription treatment fortheir CIC symptoms. Less than half (41%)reported being satisfied or completely satisfiedwith their branded prescription medication(ordinal scale of 1–7), resulting in 59% ofpatients with CIC potentially seeking newtreatment options (Fig. 1). The most frequentreasons why current and past users were notcompletely satisfied with their branded pre-scription were lack of efficacy (55%) and pres-ence of side effects (35%). On average, patientsreported that their prescription therapy pro-vided relief of symptoms after 3 days (mean,2.7 days), with only 26% reporting that theyachieved relief from their CIC symptoms within1 day. In contrast, the majority of all patients(57%) agreed that they expected their prescrip-tion treatment should work within 24 h. Ofpatients who initiated treatment with a pre-scription therapy and received relief within

24 h, 74% reported satisfaction with the timethat the treatment took to work. Overall satis-faction with time to relief was higher amongpatients who were taking prescription treat-ments for their CIC symptoms (56%) comparedto patients taking OTC laxatives (40%).

Despite using a prescription treatment, 86%of these patients reported a wide variety ofresidual CIC symptoms (multiple-choice list).Of those patients still experiencing CIC symp-toms despite prescription therapy, the mostcommon remaining CIC symptoms were diffi-culty with bowel movement and infrequentstools, followed by abdominal symptoms ofdiscomfort and bloating/distension (Table 5).

Challenges to the Management of CICSymptoms

Despite the availability of various OTC andprescription therapies, all HCPs indicated thatCIC is a challenging disorder to manage

Fig. 1 Experience with current prescription therapies for the treatment of CIC. Left percentages of patients who had everused any treatment for CIC. Branded Rx* includes linaclotide and lubiprostone. Rx prescription

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(Table 6). Only 22% of HCPs reported beingsatisfied or completely satisfied with currentprescription treatments, with 78% feeling thatthere is room for improvement. Inadequatetreatment response rates (55%) and patientadherence or compliance (55%) were the mostcommon challenges reported (multiple-choicelist), followed by the lack of CIC-specific treat-ment options (34%) and the management oftreatment-emergent diarrhea (34%). Of patientswith CIC who discontinued their prescriptiontreatment, 53% did so because of treat-ment-emergent diarrhea and 36% did sobecause of lack of efficacy. One-quarter (28%) ofCIC patients reported experiencing diarrheawhile taking an OTC laxative or prescriptiontreatment, with this proportion increasing to34% in patients with more severe CIC. Mostpatients (70%) did not agree with the statementthat diarrhea is an acceptable outcome of takinga medication to relieve symptoms of constipa-tion, while 40% agreed with the statement thatdiarrhea is a sign that my medication(s) is/are

working. Only 16% of HCPs believed that diar-rhea was a sign that the CIC treatment wasworking, with 89% of HCPs expressing thatdiarrhea was not an acceptable outcome oftreatment. Furthermore, HCPs indicated thatthey believed that diarrhea prevents patientsfrom enjoying daily activities (42%), causespatients to travel less (40%), and results inembarrassment due to having to use the bath-room frequently (37%).

DISCUSSION

The BURDEN-CIC study is one of the largestpatient-based studies conducted to understandthe management pathway, overall satisfactionwith care, and unmet treatment needs ofpatients with CIC. In addition, BURDEN-CIC isthe first study of its kind to compare and con-trast the opinions of HCPs with those of indi-viduals with CIC so as to more fully understandthe care pathway, treatment pattern, and atti-tudes about available treatments for patientsdiagnosed with CIC in the US. While CICrespondents and HCPs demonstrated alignmentregarding the CIC symptom bothersomenessand impact on activities of daily living andquality of life, as well as dissatisfaction withcurrent CIC treatments, there were also areas inwhich patients and HCPs diverged in their per-ceptions of CIC.

The findings from the BURDEN-CIC studyare consistent with those reported previouslyregarding the bothersomeness of CIC symptomsand the overall burden on daily activities, aswell as the low levels of satisfaction and highdegrees of frustration with currently availabletreatment options for CIC [4, 9, 10]. Of theBURDEN-CIC respondents, 40% were satisfiedor completely satisfied with OTC laxatives andonly 56% of patients reported being satisfied orcompletely satisfied with their current pre-scription therapy, citing inadequate efficacyand general side effects as top reasons for notbeing satisfied. As early as 2007, Johanson et al.[4] found that 47% of CIC patients were notcompletely satisfied with their current CICtreatment, with 82% citing efficacy and 16%citing adverse effect concerns as the reasons for

Table 5 Symptoms still experienced by patients with CICdespite current prescription treatment

Symptoms CIC patientsa

n5 218 (%)

Difficulty with bowel movement 35

Infrequent stools 30

Abdominal discomfort 29

Bloating/Distension 27

Straining 26

Feeling of incomplete bowel

movement

26

Hard, lumpy, or pebble-like stools 21

Stomach cramps 13

Nausea 9

Bleeding (blood on stool, toilet paper,

or in toilet bowl)

4

Rectal pain 4

a Patients who currently used prescription CIC treatmentand whose constipation symptoms were not relieved all thetime with that prescription

Adv Ther (2017) 34:2661–2673 2669

dissatisfaction. In an international survey oflaxative satisfaction [10], only 28% of CICrespondents were satisfied or very satisfied withtheir current laxative and 28% reported beingdissatisfied or very dissatisfied. This survey alsofound that there was no relationship betweenlaxative type and degree of satisfaction [10].Despite therapeutic advances with newer med-ications, new information from BURDEN-CICidentified that both patients and HCPs still havea high level of dissatisfaction with the level ofrelief provided with fiber, OTC laxatives, andprescription therapies.

Although constipation has been traditionallyviewed and managed according to infrequencyof bowel movements, the BURDEN-CIC studyhighlights that CIC is a chronic, multi-symp-tom disorder with a high level of patient burdenrequiring an individualized approach to patientmanagement. Respondents entering BUR-DEN-CIC were heterogeneous as indicated by awide range of clinical symptoms with varyingdegrees of severity and burden. In the CIC sur-vey by Johanson et al. [4], more thanthree-quarters (76%) of CIC respondents ratedtheir constipation as somewhat, very, or extre-mely bothersome, in comparison to 61% ofpatients in this study. Heidelbaugh et al. [9]found that constipation was rated as very orextremely bothersome in 62% of CIC patientswith abdominal symptoms and 40% of CICpatients without abdominal symptoms. TheCIC symptoms most commonly reported asvery or extremely bothersome from the

Johanson et al. survey included bloating,straining, hard stool consistency, and infre-quent bowel movement [4], whereas the topthree most bothersome symptoms reported inBURDEN-CIC were difficulty with bowel move-ment, straining, and abdominal pain/discom-fort. When respondents were asked to rank thesingle most bothersome symptom, the sameorder was observed: difficulty with bowelmovement (25%), straining (13%), andabdominal pain (11%). These data adhere to theacknowledgement by the Rome Committee thatCIC and IBS-C reside on a continuum, andthose 11%, while still fitting the diagnostic cri-teria for CIC, may reside closer to IBS-C on thespectrum. These results underscore the notionthat CIC is a heterogeneous condition, with thebothersomeness of symptoms relying primarilyon patient perception. While patients catego-rized here as having more severe CIC may havereported a higher intensity in symptom burdenand impairment in activities of daily living, theoverall therapeutic approach to patient man-agement did not vary considerably.

Across several studies examining the impactof CIC on quality of life, a quantifiable negativeimpact of CIC symptomatology on workplaceand school productivity has been consistentlydemonstrated. Johanson et al. [4] found that73% of respondents reported that CIC symp-toms impacted personal activities, and 69%reported some degree of productivity impair-ment, with work or school missed on an averageof 2.4 days/month. Interestingly, Heidelbaugh

Table 6 Greatest perceived challenges by HCPs to the management of patients with CIC

GE n5 155 (%) PCP n5 76 (%) NP n5 50 (%) PA n5 50 (%)

Inadequate response rates to currently available

treatment(s) for CIC

64 54 44 40

Patient adherence/non-compliance issues 52 50 58 70

Lack of treatment options for CIC 40 28 38 20

Managing treatment-related diarrhea 36 32 32 36

Managing treatment-related side effects other

than diarrhea

29 21 22 24

Lack of treatment guidelines 23 33 38 18

GE gastroenterologist, NP nurse practitioner, PA physician assistant, PCP primary care physician

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et al. [9] found that productivity was disruptedan average of 3.2 days/month in CIC patientswith abdominal symptoms resultingin* 1 day/month of work or school missed dueto CIC symptoms. In the BURDEN-CIC study,60% of respondents reported that CIC symp-toms impacted personal activities at least1 day/month. In addition, 25% of respondentsin BURDEN-CIC reported that they missed* 60 days per year of work or school(5 days/month). Lastly, 14% of CIC respondentsreported that they had visited the ER at leastonce in the past year, which may seem like arelatively high number [12–14], however, thispercentage is in close alignment with the 16%of patients that the GEs in this study who reg-ularly treat CIC patients believed visited the ERfor constipation-related symptoms.

Patients and HCPs alike expressed a highlevel of frustration and stress with the inabilityof current OTC laxatives and prescription ther-apies to provide symptomatic relief, butacknowledged that this was a consequence ofhaving to manage the disorder appropriatelyand saw no real alternative. Further, wheresymptomatic relief was achieved with prescrip-tion treatment options, the side effect profile ofthese agents (primarily diarrhea) had a signifi-cant impact on activities of daily living and,consequently, treatment satisfaction. Indeed,both HCPs and patients were aligned in theirattitudes of treatment-related diarrhea, with themajority of HCPs (89%) and patients (70%)expressing that diarrhea was not an accept-able treatment outcome. Of particular interestwas the direct correlation observed betweenpatients and HCPs in relation to the bother-someness and the prevalence of individual CICsymptoms, as well as the correlation betweenthe psychological toll, impact on quality of life,and the degree of disease severity.

Although the BURDEN-CIC study identifieda high level of dissatisfaction among patientsand HCPs with current OTC and prescriptiontreatment options, the results may be limited bythe study design. The population of HCPs,though screened for experience in the man-agement of patients with CIC, may be self-se-lected based on study participation interest andwere not necessarily the HCPs who treated the

patient respondents. Finally, respondents withCIC were identified as having CIC either basedon patient report or based on a screeningquestionnaire using Rome IV criteria.

CONCLUSION

The BURDEN-CIC study is the first large-scalepatient and HCP survey to highlight the frus-tration and high level of dissatisfaction withOTC laxatives and prescription therapies in themanagement of CIC. Despite this awareness of aheightened sense of frustration for individualssuffering from CIC, there was not a completealignment between patients and HCPs regard-ing overall treatment outcomes. While HCPsexpressed dissatisfaction with overall expecta-tions of treatments, many patients have becomeaccepting of the physical and social limitationsof the disorder. The notion that patients areaccepting of CIC as part of their daily lifewhereas HCPs believe patients are obsessed withCIC symptoms is an insight that may be a subtleyet important attitudinal disconnect betweenpatients and their healthcare providers. HCPsalso expressed dissatisfaction with the efficacyof current treatments—especially in regard totreatment-related diarrhea—whereas manypatients felt that there was little else that couldbe done to help manage their condition. Inter-estingly, only 16% of patients in BURDEN-CICindicated currently taking a prescription CICtreatment, and in consideration of the highlevel of dissatisfaction with OTC treatments,another study examining the barriers to pre-scribing branded medications may be of interestto better understand this poor utilization.

The BURDEN-CIC study emphasizes theunmetneeds ofCICpatients aswell as thoseof theHCPs who treat these patients. Ongoing dialogueand additional treatment options are neededbetween HCPs and CIC patients to ensure appro-priate treatment expectations are achieved.

ACKNOWLEDGMENTS

Synergy Pharmaceuticals Inc. provided fundingfor this study, article processing charges and the

Adv Ther (2017) 34:2661–2673 2671

open access fee. All authors had full access to allthe data in this study and take completeresponsibility for the integrity of the data andaccuracy of the data analysis. Writing and edi-torial support were provided by Mary Tom,PhD, Nicole Coolbaugh, and Philip Sjostedt,BPharm, of The Medicine Group (New Hope,PA, USA). This support was funded by SynergyPharmaceuticals Inc. All named authors meetthe International Committee of Medical JournalEditors (ICMJE) criteria for authorship for thismanuscript, take responsibility for the integrityof the work as a whole, and have given finalapproval to the version to be published.

Disclosures. Lucinda A. Harris has partici-pated in advisory boards and has served as aconsultant for Synergy Pharmaceuticals Inc.Eamonn M.M. Quigley has participated inadvisory boards and has served as a consultantfor Synergy Pharmaceuticals Inc. Leslie Magnusis an employee and stockholder in SynergyPharmaceuticals Inc. John Horn and MicheleKissous-Hunt have nothing to disclose.

Compliance with Ethics Guidelines. Thepatient protocol and associated materials werereviewed and approved by the Western Insti-tutional Review Board. Both the Patient andHCP questionnaires were conducted by GfKaccording to the globally accepted standards ofgood clinical practice (as defined in the Inter-national Conference on Harmonisation E6Guideline for Good Clinical Practice), inaccordance with the Health Insurance Porta-bility and Accountability Act, and in keepingwith local regulations. Informed consent wasobtained from all respondents for being inclu-ded in the study.

Open Access. This article is distributedunder the terms of the Creative CommonsAttribution-NonCommercial 4.0 InternationalLicense (http://creativecommons.org/licenses/by-nc/4.0/), which permits any noncommercialuse, distribution, and reproduction in anymedium, provided you give appropriate creditto the original author(s) and the source, providea link to the Creative Commons license, andindicate if changes were made.

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