Interstitial Cystitis/Bladder Pain Syndrome: Establishing Drug Development Programs for Treatment: Draft Guidance for Industry

Administrative draft guidance, not enacted legislation. This captured publisher edition preserves the listed document and attachments; later developments are not independently consolidated.

43360869dft.docx
05/09/23
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DRAFT GUIDANCE
This guidance document is being distributed for comment purposes only.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publication in the Federal Register of the notice announcing the availability of the draft
guidance.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

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 FEATURES–KEY
CONSIDERATIONS ........................................................................................................ 3
IV. 	CLINICAL TRIAL DESIGN FEATURES–KEY CONSIDERATIONS .................... 5
A. 	Enrollment Criteria ....................................................................................................................... 5
B. 	Clinical Trials Efficacy Endpoints ............................................................................................... 6
C. 	Other Considerations..................................................................................................................... 6
D. 	Hunner’s Lesions Subpopulation ................................................................................................. 7
E. 	Selecting Potential PRO and Other Secondary Endpoints for IC/BPS Clinical Trials ........... 8

Contains Nonbinding Recommendations
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1
Interstitial Cystitis/Bladder Pain Syndrome: Establishing Drug	1
Development Programs for Treatment	2
Guidance for Industry1
3
4
5
6
This draft guidance, when finalized, will represent the current thinking of the Food and Drug	7
Administration (FDA or Agency) on this topic. It does not establish any rights for any person and is not	8
binding on FDA or the public. You can use an alternative approach if it satisfies the requirements of the	9
applicable statutes and regulations. To discuss an alternative approach, contact the FDA staff responsible	10
for this guidance as listed on the title page.	11
12
13
14
I. 	INTRODUCTION	15
16
This guidance provides recommendations for clinical drug development for drugs intended to treat	17
patients with interstitial cystitis/bladder pain syndrome (IC/BPS). This guidance incorporates	18
advice FDA received at a December 2017 advisory committee meeting2 on appropriate patient	19
selection criteria and trial design features, including enrollment criteria and acceptable efficacy	20
endpoints for drugs intended to treat IC/BPS.	21
22
In general, FDA’s guidance documents do not establish legally enforceable responsibilities.	23
Instead, guidance documents describe the Agency’s current thinking on a topic and should be	24
viewed only as recommendations, unless specific regulatory or statutory requirements are cited.	25
The use of the word should in Agency guidance documents means that something is suggested or	26
recommended, but not required.	27
28
Although this guidance discusses the selection of endpoints for clinical trials, it does not address	29
detailed design considerations for patient-reported outcome (PRO) instruments. Those issues are	30
addressed in the FDA guidance for industry Patient-Reported Outcome Measures: Use in	31
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.

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Medical Product Development to Support Labeling Claims (December 2009)3 and the FDA	32
Patient-Focused Drug Development (PFDD) guidance series.4	
33
34
35
II. 	BACKGROUND	36
37
IC/BPS is a complex, poorly understood heterogeneous syndrome of unknown etiology.	38
39
Interstitial cystitis (IC) was first characterized over 100 years ago in patients as a symptom	40
complex with these two factors:	41
42
• 	Bladder pain related to bladder filling	43
• 	Historical pathognomonic cystoscopic finding of Hunner’s lesion5 in the bladder	44
45
In the intervening years, beginning in the 1970s and 1980s, there began a gradual	46
acknowledgment that IC might encompass more diverse forms of the disorder than solely	47
identifying patients with Hunner’s lesions (mucosal lesions or ulcerations seen with or without	48
hydrodistention of the bladder). The disorder definition was expanded to include patients with	49
very similar symptoms but not necessarily requiring the presence of Hunner’s lesions on	50
cystoscopic examination.	51
52
Clinical IC management has evolved and expanded to include patients with symptoms of pain or	53
discomfort and accompanying urinary symptoms, and with or without obvious bladder	54
inflammation, which encompasses a very heterogeneous patient population, hereafter referred to	55
as IC/BPS.	56
57
Currently, there are no FDA-authorized diagnostic laboratory tests or biomarkers to establish IC/BPS	58
presence or response to therapy. There is wide variability in IC/BPS diagnostic criteria, which results	59
in patient population heterogeneity, complicating development of drugs for widespread use among	60
all patient subpopulations.	61
62
In general, current IC/BPS clinical diagnosis requires the following:	63
64
• 	Chronic pain or discomfort localized to the bladder with the following variabilities:	65
66
– 	Can be related to bladder filling and/or voiding	67
– 	Can be constant, of variable intensity, or intermittent in nature	68
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 FDA’s 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):203–212.

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3
69
• 	Accompanying lower urinary tract symptoms such as urinary frequency, urgency, or	70
nocturia	71
72
• 	Exclusion of other disorders or conditions that can have similar presentations, such as	73
malignancy, any surgically diagnosed endometriosis, chronic prostatitis, and bladder	74
outlet obstruction	75
76
• 	Cystoscopy may show bladder inflammation, including Hunner’s lesions or other	77
nonspecific pathology, but also can be normal.	78
79
80
III. 	EARLY DRUG DEVELOPMENT PROGRAM FEATURES–KEY	81
CONSIDERATIONS	82
83
Current IC/BPS clinical diagnosis criteria encompasses a very heterogeneous patient population	84
who present with a common symptom: pain or discomfort localized to the bladder. Historically,	85
this has resulted in difficulty developing drug products intended for use in a heterogenous patient	86
population. Early clinical trials during drug development should focus on well-defined IC/BPS	87
populations with similar clinical features in addition to pain or discomfort localized to the	88
bladder. This approach may better inform the selection of clinically meaningful efficacy	89
endpoints and outcomes for future studies.	90
91
Sponsors are encouraged to assess dosing strategies, including dose-finding. In addition, drug	92
programs should explore multiple efficacy endpoints, and collect safety information during early	93
drug development to inform design strategy and selection of clinically meaningful endpoints for	94
later studies.	95
96
Patients’ experience with IC/BPS symptoms may vary (e.g., symptom type, severity, and	97
duration). It is important to incorporate the patient’s voice during early drug development.	98
Obtaining information from patients can better define the appropriate target population (e.g.,	99
IC/BPS patient subpopulations) and identify what matters most to patients regarding their	100
condition to inform endpoint selection. Sponsors should specify and define concepts (e.g.,	101
symptoms, functional impacts) early in development that are both relevant and important to	102
patients with IC/BPS. These concepts are more likely to lead to demonstration of clinically	103
meaningful and interpretable changes in later planned clinical trials. Identification of concepts	104
should come from patient input (e.g., conducting patient interviews, identifying literature related	105
to previously conducted patient qualitative studies). The Agency refers sponsors to the following	106
guidances for industry, FDA staff, and other stakeholders for more details about the collection of	107
evidence to inform the patient experience and obtain information from patients, caregivers, and	108
other relevant stakeholders:	109
110

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• 	Patient-Focused Drug Development: Collecting Comprehensive and Representative	111
Input (June 2020)6	
112
113
• 	Patient-Focused Drug Development: Methods to Identify What Is Important to Patients	114
(February 2022)	115
116
Once concepts from patient input are identified, sponsors should select and prioritize fit-for-	117
purpose patient-reported outcome (PRO) assessments and related endpoints to assess the targeted	118
concepts in their phase 2 clinical trials.7 The Agency encourages collaboration among patient	119
groups, medical product developers, PRO developers, and other stakeholders with the goal of	120
generating publicly available fit-for-purpose8 PRO instruments for use in IC/BPS across multiple	121
medical product development programs.9	
122
123
In general, FDA recommends that early targeted IC/BPS studies assess the following concepts	124
related to the patient experience, at a minimum:	125
126
• 	Most bothersome pain or discomfort symptom(s)	127
128
• 	Accompanying urinary symptom(s) not captured by the pain or discomfort outcome (e.g.	129
urinary frequency, urgency, or nocturia)	130
131
• 	Symptom intensity/severity scoring or measurement, where applicable	132
133
• 	Symptom changes, including worsening of symptoms	134
135
• 	Functional impacts (e.g., interference with daily activities)	136
137
Sponsors may refine their IC/BPS indication during the drug development program based on	138
earlier study results to include the following:	139
140
• 	Findings in the targeted patient subpopulations	141
• 	Focused inclusion/exclusion criteria	142
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 FDA’s
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).

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• 	Diagnostic procedures follow-up or serial diagnostic procedures for confirmation of	143
effect(s)	144
145
146
IV. 	CLINICAL TRIAL DESIGN FEATURES–KEY CONSIDERATIONS	147
148
A. 	Enrollment Criteria	149
150
Sponsors of investigational drugs intended to treat IC/BPS should consider including the	151
following for subject enrollment criteria in clinical trials:	152
153
• 	Subjects should report bladder pain and/or bladder discomfort and lower urinary tract	154
symptoms:	155
156
– 	Subjects should have at least 6 months’ duration of bladder pain and/or discomfort	157
symptom(s) before enrollment to exclude other disorders with similar presentations	158
that have a shorter time course.	159
160
– 	Subjects should have at least 6 months’ duration of one or more accompanying lower	161
urinary tract symptom(s), such as urinary frequency, urgency, or nocturia. This may be	162
intermittent or persistent.	163
164
• 	The reported symptoms (bladder pain and/or bladder discomfort and lower urinary tract	165
symptoms) should be of sufficient severity (intensity or frequency) at baseline to allow	166
for measurement of a clinically meaningful improvement with the drug (i.e., a score	167
greater than the prespecified threshold or range of thresholds for clinically meaningful	168
within-patient change). Refer to section E, Selecting Potential PRO and Secondary	169
Endpoints for IC/BPS Clinical Trials, later in this guidance.	170
171
• 	Subjects should have a cystoscopy at screening (if not obtained within the preceding 6	172
months) to exclude other conditions (e.g., transitional cell carcinoma and endometriosis,	173
etc.).	174
175
• 	Subjects may have received prior treatment(s) for IC/BPS, including surgical procedures	176
such as fulguration. In general, FDA recommends including these subjects in the trials to	177
improve the generalizability of the results unless a compelling effectiveness or safety	178
reason exists for excluding them. During the protocol trial design phase, sponsors should	179
discuss with the Agency the extent to which such subjects should be included in the trials.	180
181
• 	Subjects should undergo standard medical evaluation to exclude other conditions or	182
diseases that can cause similar symptoms, using information from medical history,	183
physical and pelvic examination findings, laboratory studies (e.g., negative urine bacterial	184
culture), and other previously performed procedures (e.g., gynecologic or prostate	185
examination, urodynamics, cystoscopy, laparoscopy, radiological studies).	186
187

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B. 	Clinical Trials Efficacy Endpoints	188
189
When developing efficacy endpoints for clinical trials, sponsors of investigational drugs intended	190
to treat IC/BPS should include both of the following as co-primary endpoints:	191
192
• 	Improvement in bladder pain and/or bladder discomfort	193
• 	Improvement in accompanying lower urinary tract symptom(s)	194
195
Sponsors are reminded that statistical improvement in these symptoms is not sufficient. Sponsors	196
should demonstrate that the changes reported are clinically meaningful to establish effectiveness	197
(refer to section E for more details about interpretation of PRO results).	198
199
If a drug is not expected to improve lower urinary tract symptoms10 based on the mechanism of	200
action specific for IC/BPS, a single primary effectiveness endpoint related to symptoms of	201
bladder pain and/or bladder discomfort may be considered, but clinical meaningfulness should	202
still be demonstrated. However, lower urinary tract symptoms should still be captured as a	203
secondary endpoint as these symptoms should not be worsened by the drug.	204
205
Sponsors should discuss with the Agency early in the development program the endpoints,	206
analyses, and anchors11 to ensure that study results are both clinically meaningful and	207
interpretable.	208
209
C. 	Other Considerations	210
211
Sponsors of investigational drugs intended to treat IC/BPS should also consider the following for	212
trial design:	213
214
• 	Treatment duration should be at least 6 months to adequately assess persistence of benefit	215
and capture intermittent symptomatic disease flares. For example, studies can be	216
designed with two treatment phases:	217
218
− 	Randomized, double-blind, placebo-controlled treatment phase of a minimum of 3	219
months or longer	220
221
− 	Extension treatment phase of a minimum of 3 months or longer following the initial	222
randomized, double-blind, placebo-controlled phase. This extension phase could be	223
open-label, crossover, or active control.	224
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 Patient’s 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.

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• 	Other randomized, double-blind, placebo-controlled study design approaches for a	226
dedicated 6-month-or-longer trial may be appropriate depending on the drug under	227
development. Sponsors should discuss their approach with the Agency before initiating	228
the trials.	229
230
• 	Sponsors should clearly prespecify in the protocol and statistical analysis plan how:	231
232
– 	Bladder pain or discomfort will be defined, documented, and treated during clinical	233
trials, including localization to bladder (i.e., physical findings, patient-derived	234
diagrams, etc.)	235
236
– 	Pain flares will be defined, documented, and treated during clinical trials	237
238
– 	Types and doses of rescue medications and accompanying sensitivity analysis will be	239
used and documented during clinical trials	240
241
The following should be discussed with the Agency in advance of clinical trial initiation:	242
243
• 	How sponsors will include targeted subgroups in their drug development program (e.g.,	244
patients with Hunner’s lesion(s)).	245
246
• 	How sponsors will ensure that there is a sufficient representative proportion of males and	247
females in the clinical trials for a general IC/BPS indication. Sponsors should take into	248
consideration the underlying proportion of males and females in the IC/BPS population	249
or subpopulation targeted by the drug. We encourage sponsors to collect information on	250
race, age, and other demographics to assist enrichment of their patient population. If the	251
product is studied only in a specific subpopulation, the labelled indication would be	252
limited to that subpopulation.	253
254
D. 	Hunner’s Lesions Subpopulation	255
256
Patients with Hunner’s lesions have been described in the literature as a “classic” IC patient	257
population, distinguishable from other IC/BPS populations. Hunner’s lesions have been	258
described as distinctive inflammatory bladder wall areas, found only at cystoscopy.12 Patients	259
with Hunner’s lesions may be a subgroup of IC/BPS patients, and alternative endpoints, such as	260
healed lesion and regression of bladder inflammation, may be considered in designing clinical	261
trials in this subgroup.13	
262
263
FDA recommends that sponsors specify criteria for diagnosis and treatment benefits if patients	264
with documented Hunner’s lesions are included in studies. Sponsors may study patients with	265
12 Fall, M, Y Logadottir, and R Peeker, 2014, Interstitial Cystitis Is Bladder Pain Syndrome With Hunner’s Lesion,
Int J Urology, 21(Suppl 1): 79–82.
13 Peeker, R, F. Aldenborg, and M Fall, 2000, Complete Transurethral Resection of Ulcers in Classic Interstitial
Cystitis, Int Urogynecol J, 11:290–295.

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Hunner’s lesions alone or include this group as a subpopulation in individual trials. Detailed	266
design features should be discussed with the Division in advance.	267
268
If studies are restricted to patients with documented Hunner’s lesions, sponsors should ensure	269
that the diagnostic tools used to diagnose Hunner’s lesions are available for use by the intended	270
provider community in the United States. If sponsors determine that they would like to develop a	271
companion diagnostic, refer to section IV.E.	272
273
• 	Sponsors should consider the following if they will recruit participants with Hunner’s	274
lesions for their trial(s):	275
276
– 	Baseline appearance of bladder pathology should be documented in a standardized	277
fashion during screening and at follow-up after treatment. For this purpose, sponsors	278
can opt to use a standard representative bladder diagram, photographic imagery, or	279
videography.	280
281
– 	Resolution of Hunner’s lesions should correlate with improvement in a clinical	282
outcome in the IC/BPS population.	283
284
• 	Sponsors that choose to adopt Hunner’s lesions as an inclusion criterion for trial entry	285
should discuss their approach in advance with the Agency. Sponsors that select patients	286
with Hunner’s lesions for their trials should provide specific guidance to clinicians about	287
how these lesions were identified to ensure that providers who are not familiar with	288
identification of these lesions will be able to select appropriate patients for treatment.	289
290
E. 	Selecting Potential PRO and Other Secondary Endpoints for IC/BPS Clinical	291
Trials	292
293
IC/BPS is a symptomatic condition, so use of a PRO assessment is the most appropriate clinical	294
outcome assessment for evaluating changes in symptoms. A separate PRO assessment can also	295
be used to evaluate the impacts of IC/BPS symptoms on activities of daily living (e.g.,	296
functioning). Then these PRO assessments can be used to better assess impacts of the	297
investigational drugs on IC/BPS symptoms. It is critical that sponsors use fit-for-purpose PRO	298
instruments to assess IC/BPS symptoms (including lower urinary tract symptoms).14 FDA	299
encourages sponsors to seek Agency input as early as possible and at important milestones	300
throughout the drug development process to ensure the inclusion of fit-for-purpose PRO	301
instruments in phase 3 trials.	302
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 Patient’s 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.

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• 	Considerations for selecting assessments of bladder pain and/or bladder discomfort in	304
patients with IC/BPS include:	305
306
– 	Patient input to understand how to describe and qualify pain and/or discomfort (with	307
bladder empty or full, relief or not relief with voiding) that is consistent with reported	308
symptom changes	309
310
– 	Inclusion of pain and/or discomfort type in the question stem (e.g., localization of	311
pain, localization of discomfort)	312
313
– 	Inclusion of pictorial diagram identifying the area where bladder pain and/or bladder	314
discomfort may present	315
316
– 	Assessments with a recall period15 (including patient diaries, if appropriate) that is	317
suitable for how bladder pain and/or bladder discomfort presents in the target	318
population (e.g., variability, duration (chronic versus episodic), frequency, and/or	319
intensity)	320
321
• 	Considerations for selecting assessments of functioning in study participants with IC/BPS	322
include:	323
324
– 	Assess bladder pain and/or bladder discomfort in relation to how it interferes with a	325
patient’s ability to perform activities of daily living to provide direct evidence of	326
whether there is an impact on a patient’s function.	327
328
– 	Provide detailed evidence (i.e., qualitative and quantitative data) that the instrument is	329
fit-for-purpose for the context of their drug development program. The Agency is	330
open to evaluating existing or modified PRO instruments for use in the IC/BPS	331
population.	332
333
Piloting the proposed PRO instruments in phase 2 trials provides opportunities to evaluate the	334
instruments’ measurement properties (reliability, validity, and ability to detect change), to	335
develop and propose an appropriate scoring algorithm, to document evidence to support a	336
definition of clinically meaningful within-patient change in scores, and to confirm the endpoint	337
definition before use in phase 3 trials.	338
339
• 	To interpret PRO endpoint results, FDA has the following recommendations:	340
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 Patient’s 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.

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– 	Propose an appropriate range of within-patient score change that patients consider to	342
be clinically meaningful using anchor-based methods supplemented with anchor-	343
based empirical cumulative distribution function curves.	344
345
– 	Anchor each pain or discomfort assessment and functioning assessment. The sponsor	346
should generate an anchor scale specific to bladder pain and/or bladder discomfort	347
and an anchor scale specific to functioning to provide the most direct evidence for	348
evaluating clinically meaningful patient-level improvement.	349
350
– 	Develop anchor scales to assess at baseline (where applicable) and at the same time	351
points as the target PRO–derived endpoint(s). These anchors should be clearly stated	352
in the protocol and statistical analysis plan. At a minimum, the following anchor	353
scales should be used to generate a threshold for clinically meaningful within-patient	354
change:	355
356
 	Static current state patient global impression rating of severity/status scale	357
 	Patient global impression of change scale	358
359
Secondary Endpoints:	360
361
Sponsors may choose to capture other exploratory or diagnostic endpoint(s) in their drug	362
development program. The following points can be considered:	363
364
• 	No specific biomarkers or other laboratory tests have been associated with change in the	365
diagnosis or changes in symptomatology in patients with IC/BPS to date. The Agency	366
will consider new biomarkers and laboratory assessments relevant to the development of	367
therapeutic products seeking to treat IC/BPS.	368
369
• 	For sponsors considering developing a therapeutic product for an IC/BPS indication with	370
a companion diagnostic device, FDA recommends that they request a meeting with the	371
relevant device and therapeutic product review divisions to ensure that the development	372
plan will provide sufficient data to establish the safety and effectiveness of both the	373
companion diagnostic device and the therapeutic product.16	
374
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 FDA’s
current thinking on this topic.