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Clinical Investigations of Devices Indicated for the Treatment of Urinary Incontinence - Guidance for Industry and FDA Staff

FinalCenter for Devices and Radiological Health03/07/2011
Risk AnalysisData IntegrityInformed ConsentRandomizationBlindingRandomized Controlled Trial

Description

For questions regarding this document, contact John Baxley at (301) 796-6549 or via email atJohn.Baxley@fda.hhs.gov.

Key Topics

Terms and concepts identified from this document

Scope & Applicability

Product Classes

5
medical devices indicated for the treatment of urinary incontinence

Scope of the guidance document

Urinary Incontinence Device

Guidance focuses on clinical investigations for these specific devices.; Clinical investigations of devices indicated for the treatment of urinary incontinence; certain prior incontinence treatments may confound the study results

Class I Device

Low risk medical devices

Class II Device

Devices subject to section 522 postmarket surveillance orders; devices subject to postmarket surveillance orders

Class III Device

Generally recommended for Enhanced Documentation; Regulatory classification mentioned for implantable sensors and HPV tests; Mentioned in the context of an in vitro nucleic acid test for CMV DNA.

Stakeholders

6
Sponsor

Entity responsible for submitting applications under section 524B

trained and qualified monitor

identification of a trained and qualified monitor for monitoring procedures

Pediatric Patients

Dosage recommendations for pediatric subpopulations

Clinical Events Committee

An independent third-party body that can categorize adverse events.

Institutional Review Board

Governs top dose in clinical studies

investigator

facilitate discussions between a prospective subject and an investigator; Responsible for conducting research and providing informed consent

Regulatory Context

Regulatory Activities

8
clinical investigations

FDA-regulated studies where electronic source data is captured

Section 522 study

postmarket surveillance study required by statutory authority

Marketing Submission

Recommendations for contents of submissions for AI-enabled devices; sponsors provide device description and labeling

Pilot Study

Used to help power and carry out subsequent pivotal studies.

Pivotal Study

Later stage clinical investigations requiring robust statistical validity

510(k)

Premarket notification submission type

PMA

Premarket Approval Application

IDE

Investigational Device Exemption submissions; Submission Documentation for Investigational Device Exemptions; Investigational Device Exemption submission recommendations

Document Types

10
Case Report Forms

Used to delineate dose and timing of administration

patient discontinuation information form

should include the date and reason for patient discontinuation

adverse events form

should identify and describe each adverse event

protocol deviation form

should identify and describe each protocol deviation

concomitant medication form

should list all medications and dietary supplements taken by the subject

post-treatment evaluation forms

should include all data collected at each follow-up visit

treatment information form

should include all relevant information regarding the treatment procedure

pre-treatment evaluation form

should include all relevant information from the pre-treatment evaluation

Informed Consent Document

must include reasonably foreseeable risks or discomforts

Statistical Analysis Plan

Document for protocol execution; The sponsor should develop a statistical analysis plan that is consistent with the trial protocol; Deviations from this plan must be justified

Attributes

10
safety and effectiveness

Primary outcomes to be measured in the study

Inclusion and exclusion criteria

documentation of inclusion and exclusion criteria in pre-treatment form

Covariate

recommend the protocol describe comprehensive covariate analyses

Post-void residual urine volume

Uroflowmetry should include a measure of PVR

Superiority Delta

clinically meaningful level of improvement

Non-inferiority Delta

maximum tolerable difference that is clinically insignificant

Primary Endpoint

Capable of providing clinically relevant evidence related to the primary objective

Significant Risk

Risk classification for medical device clinical investigations.; A classification for medical device studies.; A risk determination for a clinical study.

Primary Effectiveness Endpoint

Specific outcome measure for the study

Primary Safety Endpoint

Specific outcome measure for the study

Technical Details

Substances

2
Injectable Bulking Agent

Example of a device where randomized studies compare safety and effectiveness.; subjects treated previously with a device type similar to the one under investigation

Injectable Bulking Agents

device material used near the bladder

Testing Methods

10
randomized, controlled trial

Least burdensome means of collecting data to demonstrate safety and effectiveness

Sensitivity analyses

Used to evaluate the robustness of overall survival results

Holm's step-down procedure

Multiplicity adjustment strategy

Hierarchical closed test procedure

Multiplicity adjustment strategy

Bonferroni procedure

Common statistical method for addressing multiple-endpoint-related multiplicity problems; Endpoints are tested using Bonferroni procedure at each step.

Sensitivity Analysis

Performed to identify uncertainties that could affect HCEI conclusions.

Urinalysis

Clinical data required for safety evaluation; Safety assessment parameter (UA)

Pregnancy Test

screen subjects for pregnancy

Urinalysis with Urine Culture

exclude patients with active UTI

Cystometry

Pressure/flow studies used to support claims for reduction of obstruction.; assessment of intravesical and intra-abdominal pressure

Processes

4
Cystoscopy

Observation method for urinary efflux from ureteric orifices.

Block Randomization

A method to balance the assignment of subjects within each site.

Pilot Study

Initial feasibility study to gain clinical experience

Pivotal Study

Clinical investigations to collect definitive evidence of safety and effectiveness; Study initiated to provide primary clinical evidence for safety and effectiveness.

Clinical Concepts

10
Urinary incontinence

specific adverse events to be sought in the geriatric population

Intent-to-treat

recommend performing this primary analysis using the intent-to-treat (ITT) population

UTI

To assess for UTI, we recommend performing urinalysis

Urinary Tract Infection

condition posing additional risks to subjects

Pelvic Organ Prolapse

confounding condition for exclusion; exclude pelvic organ prolapse or neurologic disorders

Stress urinary incontinence

Condition for which specific quality of life changes are defined; category of incontinence for patient selection; 1-hour provocative pad weight test specifically targets stress urinary incontinence

Genitourinary events

Events associated with the urinary tract or surrounding genital region

Adverse events

Safety findings including deaths and post-mortem examinations

Stress Incontinence

Urinary loss during physical activities increasing intra-abdominal pressure; A specific category of urinary incontinence mentioned regarding pad weight testing.

Urge Incontinence

Urinary loss secondary to sudden strong desire to void; category of incontinence for patient selection

Identified Hazards

Hazards

7
placebo effect

Challenge in designing clinical studies for urinary incontinence

Placebo or Sham Effect

bias that occurs when a patient exposed to an inactive therapy believes they are being treated

Evaluator Bias

person measuring the outcome variable intentionally or unintentionally records measurements in favor of one intervention

Investigator Bias

concern in open-label comparative trials

Selection Bias

A type of bias to be addressed in the study design; Evaluation of any potential biases such as information bias and selection bias.

Electrical shock

Risk mitigated by special controls

Bias

mitigate potential unwanted bias in learning or performance estimation

Standards & References

Specifications

5
Inclusion Criteria

Subject inclusion criteria for selection and withdrawal.

Post-void residual urine volume

Secondary endpoint if device impacts bladder emptying

Leak point pressure

Urodynamic parameter recommended as a secondary endpoint

Dryness

Defined as pad weight increase of less than 1 gram for 1-hour test or 1.3 grams for 24-hour test

Exclusion Criteria

Subject exclusion criteria for selection and withdrawal.

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Related CFR Sections (15)

Enforcement Impact

Deficiencies cited in Warning Letters referencing the same regulations

Failure to obtain informed consent
5
Failure to ensure that the investigation was conducted according to the investigational plan
4
Misbranded under section 502(o)
2
Failure to submit an Investigational New Drug application (IND)
2
Adulterated under section 501(f)(1)(B)
2
Failure to ensure proper monitoring of the investigation
2
Failure to immediately conduct an evaluation of unanticipated adverse device effects
1
Failure to secure clinical investigator's compliance
1
Adulterated device
1
Failure to validate manufacturing process changes
1

Recent Cases

Related Warning Letters (10)

Related MFDS Guidelines

Korean regulatory guidelines covering similar topics

See Also (8)