Interstitial Cystitis/Bladder Pain 
Syndrome: Establishing Drug 
Development Programs for Treatment 
Guidance for Industry 
 
DRAFT GUIDANCE 
 
This guidance document is being distributed for comment purposes only. 
 
Comments and suggestions regarding this draft document should be submitted within 60 days of 
publication in the Federal Register of the notice announcing the availability of the draft 
guidance. Submit electronic comments to https://www.regulations.gov. Submit written 
comments to the Dockets Management Staff (HFA-305), Food and Drug Administration, 5630 
Fishers Lane, Rm. 1061, Rockville, MD 20852. All comments should be identified with the 
docket number listed in the notice of availability that publishes in the Federal Register. 
 
For questions regarding this draft document, contact Margaret Kober at 301-796-0934. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
U.S. Department of Health and Human Services 
Food and Drug Administration 
Center for Drug Evaluation and Research (CDER) 
 
June 2023 
Clinical/Medical 
Revision 1
43360869dft.docx 
05/09/23   
Interstitial Cystitis/Bladder Pain 
Syndrome: Establishing Drug 
Development Programs for Treatment 
Guidance for Industry 
 
Additional copies are available from: 
 
Office of Communications, Division of Drug Information 
Center for Drug Evaluation and Research 
Food and Drug Administration 
10001 New Hampshire Ave., Hillandale Bldg., 4th Floor 
Silver Spring, MD  20993-0002 
Phone: 855-543-3784 or 301-796-3400; Fax: 301-431-6353; Email: druginfo@fda.hhs.gov 
https://www.fda.gov/drugs/guidance-compliance-regulatory-information/guidances-drugs 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
U.S. Department of Health and Human Services 
Food and Drug Administration 
Center for Drug Evaluation and Research (CDER) 
 
June 2023 
Clinical/Medical 
Revision 1 
   
TABLE OF CONTENTS 
 
I.  INTRODUCTION............................................................................................................. 1 
II.  BACKGROUND ............................................................................................................... 2 
III.  EARLY DRUG DEVELOPMENT PROGRAM FEATURESKEY 
CONSIDERATIONS ........................................................................................................ 3 
IV.  CLINICAL TRIAL DESIGN FEATURESKEY CONSIDERATIONS .................... 5 
A.  Enrollment Criteria ....................................................................................................................... 5 
B.  Clinical Trials Efficacy Endpoints ............................................................................................... 6 
C.  Other Considerations..................................................................................................................... 6 
D.  Hunners Lesions Subpopulation ................................................................................................. 7 
E.  Selecting Potential PRO and Other Secondary Endpoints for IC/BPS Clinical Trials ........... 8 
 
  Contains Nonbinding Recommendations 
  Draft  Not for Implementation 
1  Interstitial Cystitis/Bladder Pain Syndrome: Establishing Drug 
2  Development Programs for Treatment 
3  Guidance for Industry1 
4   
5   
6   
7  This draft guidance, when finalized, will represent the current thinking of the Food and Drug 
8  Administration (FDA or Agency) on this topic.  It does not establish any rights for any person and is not 
9  binding on FDA or the public.  You can use an alternative approach if it satisfies the requirements of the 
10  applicable statutes and regulations.  To discuss an alternative approach, contact the FDA staff responsible 
11  for this guidance as listed on the title page. 
12   
13   
14   
15  I.  INTRODUCTION 
16   
17  This guidance provides recommendations for clinical drug development for drugs intended to treat 
18  patients with interstitial cystitis/bladder pain syndrome (IC/BPS). This guidance incorporates 
19  advice FDA received at a December 2017 advisory committee meeting2 on appropriate patient 
20  selection criteria and trial design features, including enrollment criteria and acceptable efficacy 
21  endpoints for drugs intended to treat IC/BPS.  
22   
23  In general, FDAs guidance documents do not establish legally enforceable responsibilities. 
24  Instead, guidance documents describe the Agencys current thinking on a topic and should be 
25  viewed only as recommendations, unless specific regulatory or statutory requirements are cited. 
26  The use of the word should in Agency guidance documents means that something is suggested or 
27  recommended, but not required.  
28   
29  Although this guidance discusses the selection of endpoints for clinical trials, it does not address 
30  detailed design considerations for patient-reported outcome (PRO) instruments. Those issues are 
31  addressed in the FDA guidance for industry Patient-Reported Outcome Measures: Use in 
 
1 This guidance has been prepared by the Division of Urology, Obstetrics, and Gynecology in the Center for Drug 
Evaluation and Research at the Food and Drug Administration. 
 
2 Information on the meeting of the Bone, Reproductive and Urologic Drugs Advisory Committee is available at 
https://public4.pagefreezer.com/browse/FDA/01-03-2022T00:42/https:/www.fda.gov/advisory-committees/bone-
reproductive-and-urologic-drugs-advisory-committee-formerly-reproductive-health-drugs-advisory/2017-meeting-
materials-bone-reproductive-and-urologic-drugs-advisory-committee-formerly-advisory. 
 
  1  Contains Nonbinding Recommendations 
  Draft  Not for Implementation 
32  Medical Product Development to Support Labeling Claims (December 2009)3 and the FDA 
33  Patient-Focused Drug Development (PFDD) guidance series.4 
34   
35   
36  II.  BACKGROUND 
37   
38  IC/BPS is a complex, poorly understood heterogeneous syndrome of unknown etiology.  
39   
40  Interstitial cystitis (IC) was first characterized over 100 years ago in patients as a symptom 
41  complex with these two factors:  
42   
43    Bladder pain related to bladder filling  
44    Historical pathognomonic cystoscopic finding of Hunners lesion5 in the bladder 
45   
46  In the intervening years, beginning in the 1970s and 1980s, there began a gradual 
47  acknowledgment that IC might encompass more diverse forms of the disorder than solely 
48  identifying patients with Hunners lesions (mucosal lesions or ulcerations seen with or without 
49  hydrodistention of the bladder). The disorder definition was expanded to include patients with 
50  very similar symptoms but not necessarily requiring the presence of Hunners lesions on 
51  cystoscopic examination.  
52   
53  Clinical IC management has evolved and expanded to include patients with symptoms of pain or 
54  discomfort and accompanying urinary symptoms, and with or without obvious bladder 
55  inflammation, which encompasses a very heterogeneous patient population, hereafter referred to 
56  as IC/BPS.  
57   
58  Currently, there are no FDA-authorized diagnostic laboratory tests or biomarkers to establish IC/BPS 
59  presence or response to therapy. There is wide variability in IC/BPS diagnostic criteria, which results 
60  in patient population heterogeneity, complicating development of drugs for widespread use among 
61  all patient subpopulations.  
62   
63  In general, current IC/BPS clinical diagnosis requires the following:  
64   
65    Chronic pain or discomfort localized to the bladder with the following variabilities: 
66   
67    Can be related to bladder filling and/or voiding 

68    Can be constant, of variable intensity, or intermittent in nature  

 
3 We update guidances periodically. For the most recent version of a guidance, check the FDA guidance web page at 
https://www.fda.gov/regulatory-information/search-fda-guidance-documents. 
 
4 These guidances are part of FDAs PFDD efforts in accordance with the 21st Century Cures Act and the Food and 
Drug Administration Reauthorization Act of 2017 Title I. When final, the PFDD guidance series will replace the 
2009 final PRO guidance. 
 
5 Hunner G., 1918, A Rare Type of Bladder Ulcer: Further Notes, with a Report of Eighteen Cases, JAMA, 
70(4):203212. 
 
  2  Contains Nonbinding Recommendations 
  Draft  Not for Implementation 
69   
70    Accompanying lower urinary tract symptoms such as urinary frequency, urgency, or 
71  nocturia 
72   
73     Exclusion of other disorders or conditions that can have similar presentations, such as 
74  malignancy, any surgically diagnosed endometriosis, chronic prostatitis, and bladder 
75  outlet obstruction   
76   
77    Cystoscopy may show bladder inflammation, including Hunners lesions or other 
78  nonspecific pathology, but also can be normal.  
79   
80   
81  III.  EARLY DRUG DEVELOPMENT PROGRAM FEATURESKEY 
82  CONSIDERATIONS 
83   
84  Current IC/BPS clinical diagnosis criteria encompasses a very heterogeneous patient population 
85  who present with a common symptom: pain or discomfort localized to the bladder. Historically, 
86  this has resulted in difficulty developing drug products intended for use in a heterogenous patient 
87  population. Early clinical trials during drug development should focus on well-defined IC/BPS 
88  populations with similar clinical features in addition to pain or discomfort localized to the 
89  bladder. This approach may better inform the selection of clinically meaningful efficacy 
90  endpoints and outcomes for future studies.  
91   
92  Sponsors are encouraged to assess dosing strategies, including dose-finding. In addition, drug 
93  programs should explore multiple efficacy endpoints, and collect safety information during early 
94  drug development to inform design strategy and selection of clinically meaningful endpoints for 
95  later studies. 
96   
97  Patients experience with IC/BPS symptoms may vary (e.g., symptom type, severity, and 
98  duration). It is important to incorporate the patients voice during early drug development. 
99  Obtaining information from patients can better define the appropriate target population (e.g., 
100  IC/BPS patient subpopulations) and identify what matters most to patients regarding their 
101  condition to inform endpoint selection. Sponsors should specify and define concepts (e.g., 
102  symptoms, functional impacts) early in development that are both relevant and important to 
103  patients with IC/BPS. These concepts are more likely to lead to demonstration of clinically 
104  meaningful and interpretable changes in later planned clinical trials. Identification of concepts 
105  should come from patient input (e.g., conducting patient interviews, identifying literature related 
106  to previously conducted patient qualitative studies). The Agency refers sponsors to the following 
107  guidances for industry, FDA staff, and other stakeholders for more details about the collection of 
108  evidence to inform the patient experience and obtain information from patients, caregivers, and 
109  other relevant stakeholders: 
110   
  3  Contains Nonbinding Recommendations 
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111    Patient-Focused Drug Development: Collecting Comprehensive and Representative 
112  Input (June 2020)6 
113   
114    Patient-Focused Drug Development: Methods to Identify What Is Important to Patients 
115  (February 2022) 
116   
117  Once concepts from patient input are identified, sponsors should select and prioritize fit-for-
118  purpose patient-reported outcome (PRO) assessments and related endpoints to assess the targeted 
119  concepts in their phase 2 clinical trials.7 The Agency encourages collaboration among patient 
120  groups, medical product developers, PRO developers, and other stakeholders with the goal of 
121  generating publicly available fit-for-purpose8 PRO instruments for use in IC/BPS across multiple 
122  medical product development programs.9 
123   
124  In general, FDA recommends that early targeted IC/BPS studies assess the following concepts 
125  related to the patient experience, at a minimum:  
126   
127    Most bothersome pain or discomfort symptom(s)  
128   
129    Accompanying urinary symptom(s) not captured by the pain or discomfort outcome (e.g. 
130  urinary frequency, urgency, or nocturia)  
131   
132    Symptom intensity/severity scoring or measurement, where applicable  
133   
134    Symptom changes, including worsening of symptoms 
135   
136    Functional impacts (e.g., interference with daily activities) 
137   
138  Sponsors may refine their IC/BPS indication during the drug development program based on 
139  earlier study results to include the following:  
140   
141    Findings in the targeted patient subpopulations 
142    Focused inclusion/exclusion criteria 
 
6 We update guidances periodically. For the most recent version of a guidance, check the FDA guidance web page at 
https://www.fda.gov/regulatory-information/search-fda-guidance-documents. 
 
7 See the draft guidance for industry, FDA staff, and other stakeholders Patient-Focused Drug Development: 
Selecting, Developing, or Modifying Fit-for Purpose Clinical Outcome Assessments (June 2022) and the draft 
guidance for industry Patient-Focused Drug Development: Incorporating Clinical Outcome Assessments Into 
Endpoints For Regulatory Decision-Making (April 2023). When final, these guidances will represent the FDAs 
current thinking on these topics. For the most recent version of a guidance, check the FDA guidance web page at 
https://www.fda.gov/regulatory-information/search-fda-guidance-documents. 
 
8 For purposes of this guidance, fit-for-purpose is defined as a conclusion that the level of validation associated with 
a tool is sufficient to support its context of use. See the BEST (Biomarkers, Endpoints, and other Tools) Resource, 
available at https://www.ncbi.nlm.nih.gov/books/NBK326791/?report=reader. 
 
9 See the guidance for industry and FDA staff Qualification Process for Drug Development Tools (November 2020). 
 
  4  Contains Nonbinding Recommendations 
  Draft  Not for Implementation 
143    Diagnostic procedures follow-up or serial diagnostic procedures for confirmation of 
144  effect(s) 
145   
146   
147  IV.  CLINICAL TRIAL DESIGN FEATURESKEY CONSIDERATIONS 
148   
149  A.  Enrollment Criteria 
150   
151  Sponsors of investigational drugs intended to treat IC/BPS should consider including the 
152  following for subject enrollment criteria in clinical trials:  
153   
154    Subjects should report bladder pain and/or bladder discomfort and lower urinary tract 
155  symptoms:   
156   
157    Subjects should have at least 6 months duration of bladder pain and/or discomfort 

158  symptom(s) before enrollment to exclude other disorders with similar presentations 
159  that have a shorter time course.  
160   
161    Subjects should have at least 6 months duration of one or more accompanying lower 

162  urinary tract symptom(s), such as urinary frequency, urgency, or nocturia. This may be 
163  intermittent or persistent.   
164   
165    The reported symptoms (bladder pain and/or bladder discomfort and lower urinary tract 
166  symptoms) should be of sufficient severity (intensity or frequency) at baseline to allow 
167  for measurement of a clinically meaningful improvement with the drug (i.e., a score 
168  greater than the prespecified threshold or range of thresholds for clinically meaningful 
169  within-patient change). Refer to section E, Selecting Potential PRO and Secondary 
170  Endpoints for IC/BPS Clinical Trials, later in this guidance. 
171   
172    Subjects should have a cystoscopy at screening (if not obtained within the preceding 6 
173  months) to exclude other conditions (e.g., transitional cell carcinoma and endometriosis, 
174  etc.).  
175   
176    Subjects may have received prior treatment(s) for IC/BPS, including surgical procedures 
177  such as fulguration. In general, FDA recommends including these subjects in the trials to 
178  improve the generalizability of the results unless a compelling effectiveness or safety 
179  reason exists for excluding them. During the protocol trial design phase, sponsors should 
180  discuss with the Agency the extent to which such subjects should be included in the trials. 
181   
182    Subjects should undergo standard medical evaluation to exclude other conditions or 
183  diseases that can cause similar symptoms, using information from medical history, 
184  physical and pelvic examination findings, laboratory studies (e.g., negative urine bacterial 
185  culture), and other previously performed procedures (e.g., gynecologic or prostate 
186  examination, urodynamics, cystoscopy, laparoscopy, radiological studies). 
187   
  5  Contains Nonbinding Recommendations 
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188  B.  Clinical Trials Efficacy Endpoints 
189   
190  When developing efficacy endpoints for clinical trials, sponsors of investigational drugs intended 
191  to treat IC/BPS should include both of the following as co-primary endpoints: 
192   
193    Improvement in bladder pain and/or bladder discomfort  
194    Improvement in accompanying lower urinary tract symptom(s)  
195   
196  Sponsors are reminded that statistical improvement in these symptoms is not sufficient. Sponsors 
197  should demonstrate that the changes reported are clinically meaningful to establish effectiveness 
198  (refer to section E for more details about interpretation of PRO results).  
199   
200  If a drug is not expected to improve lower urinary tract symptoms10 based on the mechanism of 
201  action specific for IC/BPS, a single primary effectiveness endpoint related to symptoms of 
202  bladder pain and/or bladder discomfort may be considered, but clinical meaningfulness should 
203  still be demonstrated. However, lower urinary tract symptoms should still be captured as a 
204  secondary endpoint as these symptoms should not be worsened by the drug. 
205   
206  Sponsors should discuss with the Agency early in the development program the endpoints, 
207  analyses, and anchors11 to ensure that study results are both clinically meaningful and 
208  interpretable.  
209   
210  C.  Other Considerations 
211   
212  Sponsors of investigational drugs intended to treat IC/BPS should also consider the following for 
213  trial design: 
214   
215    Treatment duration should be at least 6 months to adequately assess persistence of benefit 
216  and capture intermittent symptomatic disease flares. For example, studies can be 
217  designed with two treatment phases:  
218   
219    Randomized, double-blind, placebo-controlled treatment phase of a minimum of 3 
220  months or longer  
221   
222    Extension treatment phase of a minimum of 3 months or longer following the initial 
223  randomized, double-blind, placebo-controlled phase. This extension phase could be 
224  open-label, crossover, or active control.  
225   
 
10 See section II, Background, lower urinary tract symptoms such as urinary frequency, urgency, or nocturia. 
 
11 For general recommendations regarding PRO instruments and documents to be provided to FDA for review, see 
the guidance for industry Patient-Reported Outcome Measures: Use in Medical Product Development to Support 
Labeling Claims and the FDA Patient-Focused Drug Development Guidance Series for Enhancing the Incorporation 
of the Patients Voice in Medical Product Development and Regulatory Decision Making, available at 
https://www.fda.gov/drugs/development-approval-process-drugs/fda-patient-focused-drug-development-guidance-
series-enhancing-incorporation-patients-voice-medical. 
 
  6  Contains Nonbinding Recommendations 
  Draft  Not for Implementation 
226    Other randomized, double-blind, placebo-controlled study design approaches for a 
227  dedicated 6-month-or-longer trial may be appropriate depending on the drug under 
228  development. Sponsors should discuss their approach with the Agency before initiating 
229  the trials.  
230   
231    Sponsors should clearly prespecify in the protocol and statistical analysis plan how: 
232   
233    Bladder pain or discomfort will be defined, documented, and treated during clinical 

234  trials, including localization to bladder (i.e., physical findings, patient-derived 
235  diagrams, etc.)  
236   
237    Pain flares will be defined, documented, and treated during clinical trials 

238   
239    Types and doses of rescue medications and accompanying sensitivity analysis will be 

240  used and documented during clinical trials 
241   
242  The following should be discussed with the Agency in advance of clinical trial initiation: 
243   
244    How sponsors will include targeted subgroups in their drug development program (e.g., 
245  patients with Hunners lesion(s)).  
246   
247    How sponsors will ensure that there is a sufficient representative proportion of males and 
248  females in the clinical trials for a general IC/BPS indication. Sponsors should take into 
249  consideration the underlying proportion of males and females in the IC/BPS population 
250  or subpopulation targeted by the drug. We encourage sponsors to collect information on 
251  race, age, and other demographics to assist enrichment of their patient population. If the 
252  product is studied only in a specific subpopulation, the labelled indication would be 
253  limited to that subpopulation. 
254   
255  D.  Hunners Lesions Subpopulation 
256   
257  Patients with Hunners lesions have been described in the literature as a classic IC patient 
258  population, distinguishable from other IC/BPS populations. Hunners lesions have been 
259  described as distinctive inflammatory bladder wall areas, found only at cystoscopy.12 Patients 
260  with Hunners lesions may be a subgroup of IC/BPS patients, and alternative endpoints, such as 
261  healed lesion and regression of bladder inflammation, may be considered in designing clinical 
262  trials in this subgroup.13  
263   
264  FDA recommends that sponsors specify criteria for diagnosis and treatment benefits if patients 
265  with documented Hunners lesions are included in studies. Sponsors may study patients with 
 
12 Fall, M, Y Logadottir, and R Peeker, 2014, Interstitial Cystitis Is Bladder Pain Syndrome With Hunners Lesion, 
Int J Urology, 21(Suppl 1): 7982. 
 
13 Peeker, R, F. Aldenborg, and M Fall, 2000, Complete Transurethral Resection of Ulcers in Classic Interstitial 
Cystitis, Int Urogynecol J, 11:290295. 
 
  7  Contains Nonbinding Recommendations 
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266  Hunners lesions alone or include this group as a subpopulation in individual trials. Detailed 
267  design features should be discussed with the Division in advance.  
268   
269  If studies are restricted to patients with documented Hunners lesions, sponsors should ensure 
270  that the diagnostic tools used to diagnose Hunners lesions are available for use by the intended 
271  provider community in the United States. If sponsors determine that they would like to develop a 
272  companion diagnostic, refer to section IV.E. 
273   
274    Sponsors should consider the following if they will recruit participants with Hunners 
275  lesions for their trial(s):  
276   
277    Baseline appearance of bladder pathology should be documented in a standardized 

278  fashion during screening and at follow-up after treatment. For this purpose, sponsors 
279  can opt to use a standard representative bladder diagram, photographic imagery, or 
280  videography. 
281   
282    Resolution of Hunners lesions should correlate with improvement in a clinical 

283  outcome in the IC/BPS population. 
284   
285    Sponsors that choose to adopt Hunners lesions as an inclusion criterion for trial entry 
286  should discuss their approach in advance with the Agency. Sponsors that select patients 
287  with Hunners lesions for their trials should provide specific guidance to clinicians about 
288  how these lesions were identified to ensure that providers who are not familiar with 
289  identification of these lesions will be able to select appropriate patients for treatment.  
290   
291  E.  Selecting Potential PRO and Other Secondary Endpoints for IC/BPS Clinical 
292  Trials 
293   
294  IC/BPS is a symptomatic condition, so use of a PRO assessment is the most appropriate clinical 
295  outcome assessment for evaluating changes in symptoms. A separate PRO assessment can also 
296  be used to evaluate the impacts of IC/BPS symptoms on activities of daily living (e.g., 
297  functioning). Then these PRO assessments can be used to better assess impacts of the 
298  investigational drugs on IC/BPS symptoms. It is critical that sponsors use fit-for-purpose PRO 
299  instruments to assess IC/BPS symptoms (including lower urinary tract symptoms).14 FDA 
300  encourages sponsors to seek Agency input as early as possible and at important milestones 
301  throughout the drug development process to ensure the inclusion of fit-for-purpose PRO 
302  instruments in phase 3 trials. 
303   
 
14 For general recommendations regarding PRO instruments and documents to be provided to FDA for review, see 
the guidance for industry Patient-Reported Outcome Measures: Use in Medical Product Development to Support 
Labeling Claims and the FDA Patient-Focused Drug Development Guidance Series for Enhancing the Incorporation 
of the Patients Voice in Medical Product Development and Regulatory Decision Making, available at 
https://www.fda.gov/drugs/development-approval-process-drugs/fda-patient-focused-drug-development-guidance-
series-enhancing-incorporation-patients-voice-medical. 
 
  8  Contains Nonbinding Recommendations 
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304    Considerations for selecting assessments of bladder pain and/or bladder discomfort in 
305  patients with IC/BPS include: 
306   
307    Patient input to understand how to describe and qualify pain and/or discomfort (with 
308  bladder empty or full, relief or not relief with voiding) that is consistent with reported 
309  symptom changes 
310   
311    Inclusion of pain and/or discomfort type in the question stem (e.g., localization of 
312  pain, localization of discomfort) 
313   
314    Inclusion of pictorial diagram identifying the area where bladder pain and/or bladder 
315  discomfort may present 
316   
317    Assessments with a recall period15 (including patient diaries, if appropriate) that is 
318  suitable for how bladder pain and/or bladder discomfort presents in the target 
319  population (e.g., variability, duration (chronic versus episodic), frequency, and/or 
320  intensity) 
321   
322    Considerations for selecting assessments of functioning in study participants with IC/BPS 
323  include: 
324   
325    Assess bladder pain and/or bladder discomfort in relation to how it interferes with a 
326  patients ability to perform activities of daily living to provide direct evidence of 
327  whether there is an impact on a patients function. 
328   
329    Provide detailed evidence (i.e., qualitative and quantitative data) that the instrument is 
330  fit-for-purpose for the context of their drug development program. The Agency is 
331  open to evaluating existing or modified PRO instruments for use in the IC/BPS 
332  population.    
333   
334  Piloting the proposed PRO instruments in phase 2 trials provides opportunities to evaluate the 
335  instruments measurement properties (reliability, validity, and ability to detect change), to 
336  develop and propose an appropriate scoring algorithm, to document evidence to support a 
337  definition of clinically meaningful within-patient change in scores, and to confirm the endpoint 
338  definition before use in phase 3 trials. 
339   
340    To interpret PRO endpoint results, FDA has the following recommendations:   
341   
 
15 For general recommendations regarding PRO instruments and documents to be provided to FDA for review, see 
the guidance for industry Patient-Reported Outcome Measures: Use in Medical Product Development to Support 
Labeling Claims and the FDA Patient-Focused Drug Development Guidance Series for Enhancing the Incorporation 
of the Patients Voice in Medical Product Development and Regulatory Decision Making, available at 
https://www.fda.gov/drugs/development-approval-process-drugs/fda-patient-focused-drug-development-guidance-
series-enhancing-incorporation-patients-voice-medical. 
 
  9  Contains Nonbinding Recommendations 
  Draft  Not for Implementation 
342    Propose an appropriate range of within-patient score change that patients consider to 
343  be clinically meaningful using anchor-based methods supplemented with anchor-
344  based empirical cumulative distribution function curves.  
345   
346    Anchor each pain or discomfort assessment and functioning assessment. The sponsor 
347  should generate an anchor scale specific to bladder pain and/or bladder discomfort 
348  and an anchor scale specific to functioning to provide the most direct evidence for 
349  evaluating clinically meaningful patient-level improvement.   
350   
351    Develop anchor scales to assess at baseline (where applicable) and at the same time 
352  points as the target PROderived endpoint(s). These anchors should be clearly stated 
353  in the protocol and statistical analysis plan. At a minimum, the following anchor 
354  scales should be used to generate a threshold for clinically meaningful within-patient 
355  change:  
356   
357    Static current state patient global impression rating of severity/status scale 
358    Patient global impression of change scale 
359   
360  Secondary Endpoints:  
361   
362  Sponsors may choose to capture other exploratory or diagnostic endpoint(s) in their drug 
363  development program. The following points can be considered:  
364   
365    No specific biomarkers or other laboratory tests have been associated with change in the 
366  diagnosis or changes in symptomatology in patients with IC/BPS to date. The Agency 
367  will consider new biomarkers and laboratory assessments relevant to the development of 
368  therapeutic products seeking to treat IC/BPS.   
369   
370    For sponsors considering developing a therapeutic product for an IC/BPS indication with 
371  a companion diagnostic device, FDA recommends that they request a meeting with the 
372  relevant device and therapeutic product review divisions to ensure that the development 
373  plan will provide sufficient data to establish the safety and effectiveness of both the 
374  companion diagnostic device and the therapeutic product.16 
375   
 
16 See the draft guidance for industry and FDA staff Principles for Codevelopment of an In Vitro Companion 
Diagnostic Device with a Therapeutic Product (July 2016). When final, this guidance will represent the FDAs 
current thinking on this topic. 
  10