Contains Nonbinding Recommendations
Draft Not for Implementation
Clinical Considerations for Studies of 
Devices Intended to Treat Opioid Use 
Disorder
______________________________________________________________________________
Draft Guidance for Industry and
Food and Drug Administration Staff
DRAFT GUIDANCE
This draft guidance document is being distributed for comment purposes 
only.
Document issued on July 28, 2023.
You should submit comments and suggestions regarding this draft document within 90 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publication in the Federal Register of the notice announcing the availability of the draft 
guidance.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, Food and Drug Administration, 5630 Fishers Lane, 
Room 1061, (HFA-305), Rockville, MD 20852. Identify all comments with the docket number 
listed in the notice of availability that publishes in the Federal Register.
For questions about this document, contact the Office of Health Technology 5 (OHT5), 
Neurological and Physical Medicine Devices, Division 5B at 240-402-3039.
U.S. Department of Health and Human Services
Food and Drug Administration
Center for Devices and Radiological Health  Contains Nonbinding Recommendations
Draft Not for Implementation
Preface
Additional Copies
Additional copies are available from the Internet. You may also send an email request to CDRH-
Guidance@fda.hhs.gov to receive a copy of the guidance. Please include the document number 
GUI00019017 and complete title of the guidance in the request. Contains Nonbinding Recommendations
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Table of Contents
I.  Introduction .......................................................................................................................... 1
II.  Background .......................................................................................................................... 2
III.  Scope .................................................................................................................................... 2
IV.  Clinical Study Design .......................................................................................................... 3
A.  Patient Population and Assignment to Treatment and Control Groups ........................... 4
B.  Recording Medication Use ............................................................................................... 4
C.  Monitoring Prescribed and Non-prescribed Drug Use ..................................................... 4
D.  Appropriate Study Length and Evaluation ....................................................................... 5
E.  Participant Retention and Preventing Missing Data ........................................................ 5
F.  Clinical Outcomes ............................................................................................................ 6
(1)  Change in Drug Use Pattern ......................................................................................... 7
(2)  Change in OUD Disease Status Using DSM-5-TR Diagnostic Criteria ...................... 7
(3)  Reduction in Adverse Outcomes of OUD .................................................................... 8
(4)  Patient-Reported Outcome Instruments ........................................................................ 8
(5)  Other Outcome Measures ............................................................................................. 9 Contains Nonbinding Recommendations
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Clinical Considerations for Studies of 
1
Devices Intended to Treat Opioid Use 
2
Disorder
3
4 ______________________________________________________________________________
Draft Guidance for Industry and
5
Food and Drug Administration Staff
6
7
8  This draft guidance, when finalized, will represent the current thinking of the Food and Drug 
9  Administration (FDA or Agency)on this topic.  It does not establish any rights for any person 
10  and is not binding on FDA or the public.  You can use an alternative approach if it satisfies 
11  the requirements of the applicable statutes and regulations.  To discuss an alternative 
12 approach, contact the FDA staff or Office responsible for this guidanceas listed on the title 
13 page.
14
I. Introduction
15
16  The opioid overdose crisis is a serious and complex challenge 1 facing the United States. The 
17 Agency has already taken significant steps to decrease unnecessary exposure to opioids, prevent 
18 new cases of opioid use disorder (OUD)and support the treatment of peoplewith OUD.2 The 
19 Center for Devices and Radiological Health (CDRH) is committed to helping to end this national 
20 crisis.3
21
22  This guidance provides recommendations for the design of pivotal clinical studies4 for devices 
23 intended to treat OUD (hereafter OUD device studies) and used to support marketing
1 As a result of the consequences of the opioid crisis affecting the United States, on October 26, 2017, the 
Department of Health and Human Services, pursuant to section 319 of the Public Health Service Act, determined 
that a public health emergency exists nationwide. This determination has subsequently been renewed repeatedly, 
most recently on March 31, 2023. https://www.phe.gov/emergency/news/healthactions/phe/Pages/default.aspx. 
2 This timeline provides selected FDA activities and significant events related to addressing substance use and 
overdose prevention: https://www.fda.gov/drugs/information-drug-class/timeline-selected-fda-activities-and-
significant-events-addressing-substance-use-and-overdose. 
3 For example, on May 13, 2018, CDRH launched an innovation challenge for the development of devices intended 
to prevent and treat OUD. See FDA Innovation Challenge: Devices to Prevent and Treat Opioid Use Disorder. 
https://www.fda.gov/about-fda/cdrh-innovation/fda-innovation-challenge-devices-prevent-and-treat-opioid-use-
disorder 
4 21 CFR 812.3(h) defines investigation to mean a clinical investigation or research involving one or more 
subjects to determine the safety or effectiveness of a device.  For the purposes of this guidance, the terms study, 
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24 submissions. These recommendations are applicable to the design and development of clinical 
25 studies to provide a reasonable assurance of safety and effectiveness fora device intended to 
26 treat OUD. The recommendations in this guidance may also be useful for the evaluation of other 
27 types of valid scientific evidencedemonstrating clinically significant results that may be used to 
28 provide areasonable assurance ofsafety andeffectiveness. OUD device studies designed using 
29 the recommendations set out in this guidance may advance the treatment of OUD by providing
30 scientific evidence that aids FDA in determining whether there is a reasonable assurance that a 
31 device intended to treat OUD is safe and effective. These recommendations may change as more 
32 information becomes available,and the researchcommunity gains experience with different 
33 designs in relation to OUD devicestudies.
34
35 In general, FDAs guidance documents do not establish legally enforceable responsibilities. 
36 Instead, guidances describe the Agencys current thinking on a topic and should be viewed only 
37 as recommendations, unless specific regulatory or statutory requirements are cited. The use of 
38 the word should in Agency guidances means that something is suggested or recommended, but
39 not required.
II. Background
40
41 The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5-TR)defines 
42  OUD as a problematic pattern of opioid use leading to clinically significant impairment or 
43  distress, as manifested by at least two factors identified in the DSM-5-TR, occurring within a 
44  12-month period. OUD causes significant long-term impairment of physical, emotional, social, 
45  or cognitive function.5 The disorder can arise as an unintended consequence of misuse of 
46 prescription opioid pain medications, or the use of illicit drugs.  
47
48  Because of the complexity of OUD, there are many challenges in designing OUD device studies. 
49  These challenges include inaccurate participant reports of drug use, high rates of missing data, 
50  the confounding effects of concomitant drug treatments, and the need to demonstrate the 
51  durability of the devices treatment effect, which can necessitate prolonged observation. To help 
52  spur innovative options to combat the opioid overdose crisis and treat OUD, this guidance 
53  provides recommendations on the design of pivotal OUD device studies. Through these 
54  recommendations, FDA intends to aid sponsors in developing OUD device studies that provide 
55  scientific evidence used to determine whether there is a reasonable assurance of safety and 
56 effectiveness for treating OUD. 
III.  Scope
57
clinical study, trial, and investigationare used interchangeably.A medical device pivotal study is a definitive study 
in which evidence is gathered to support the safety and effectiveness evaluation of the medical device for its 
intended use.For more information on pivotal clinicalstudies, please see FDA guidance Design Considerations for 
PivotalClinical Investigations for Medical Devices, available at https://www.fda.gov/regulatory-information/search-
fda-guidance-documents/design-considerations-pivotal-clinical-investigations-medical-devices. 
5 Specific criteria are in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5-TR), 
F11.10 through F11.21.
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58 This guidance applies to pivotal clinical studies of safety and effectiveness for devices intended 
59 to treat OUD andthat are used to support marketing submissions. The principles discussed in this 
60 guidance are intended to assist sponsors and investigators designing studies that can provide a 
61 reasonable assurance of safety and effectiveness for adevice intended to treat OUD. This 
62 guidance recommends well-controlled studies for pivotal OUD device studies, but
63 recommendationswithin this guidance may beapplicable to other types of studies intended to 
64 generate valid scientific evidence that may be used in providing a reasonable assurance of safety 
65 and effectiveness. Early feasibility studies and other preliminary studies are outside the scope of 
66 this guidance.6
67
68 The following products are outside the scope of this guidance:
69   Diagnostic tests for the detectionof opioid use;
70   Devices intended to diagnose or to help determine the risk of developing OUD; 
71  Devices intended to treat pain; and
72    Combination products.7  
IV.  Clinical Study Design 
73 
74  This section of the guidance outlines recommended study design features for pivotal OUD 
75  device studies.8 Because of the large uncertainty due to subjective outcomes, placebo effects, 
76  concomitant treatments, and potential bias, among other factors, pivotal OUD device studies 
77  should be well-controlled and designed to generate valid scientific evidence that demonstrates 
78  clinically significant results. In particular, pivotal OUD device studies used to support marketing 
79  submissions should have a well-defined study population, appropriately monitor drug use, 
80  control for bias, and include an appropriate follow-up period, study participant retention plans, 
81  and data analysis plan. The study population should represent the diversity prevalent among 
82  individuals with OUD. For more information about well-controlled clinical studies, see 21 CFR 
83 860.7(f) and FDAs guidance document: Design Considerations for Pivotal Clinical 
84 Investigations for Medical Devices.
85
86  CDRH acknowledges the challenges in study methodology in the field of OUD treatment and 
87  encourages sponsors to develop alternative methodologies to overcome these challenges while 
88  still producing valid scientific evidence that can be used to support a marketing submission. In 
89  certain circumstances, FDA is open to alternative approaches to demonstrate a reasonable 
90  assurance of safety and effectiveness of devices intended to treat OUD. FDA recommends that 
91 sponsors use the Q-Submission process to discuss such approaches prior to study initiation. For 
6 For more information on early feasibility studies and other exploratory studies, please see FDA guidance 
documents, Design Considerations for Pivotal Clinical Investigations for Medical Devices, available at 
https://www.fda.gov/regulatory-information/search-fda-guidance-documents/design-considerations-pivotal-clinical-
investigations-medical-devices and Investigational Device Exemptions (IDEs) for Early Feasibility Medical Device 
Clinical Studies, Including Certain First in Human (FIH) Studies, available at https://www.fda.gov/regulatory-
information/search-fda-guidance-documents/investigational-device-exemptions-ides-early-feasibility-medical-
device-clinical-studies-including.
7 For more information about combination products, please see available resources at 
https://www.fda.gov/combination-products.
8 For further information on the determination of safety and effectiveness, see 21 CFR 860.7.
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92 details on the Q-Submission Program, please refer to FDAs guidance Requests for Feedback 
93 and Meetings for Medical Device Submissions: The Q-Submission Program.9  
A. Patient Population and Assignment to Treatment and 
94
Control Groups
95
96  When designing apivotal OUD device study, CDRH encourages sponsors to define the 
97  population the device is intended to treat by defining specific inclusion and exclusion criteria that 
98  readily translate to clinical practice. FDA believes that clearly defining the study population in 
99  practical terms will allow eventual prescribers to be confident that the evidence of effectiveness 
100  established in the OUD device studies is relevant to the patients for whom they prescribe or 
101  recommend the device. In other words, prescribers can be confident the patients for whom they 
102  prescribe the device are like those in the study population. 10 
103   
104  None of the participants, treating investigators, or evaluators should be aware of a participants 
105  treatment assignment. A demonstration of a reasonable assurance of effectiveness generally 
106  relies on a comparison of the device to a control in a way such that study results can lead to a 
107  valid conclusion that any difference between the treatment and control is caused by the device. 
108 For devices, participants in the control grouparetreated with a sham control to avoid the 
109 introduction of biases. A sham control is a treatment or procedure that is performed as a control 
110 and is similar to,but omits therapeutic elements of,the treatment or procedure under 
111 investigation. Effective controls are particularly important inpivotal OUD device studies.CDRH 
112 recognizes that designing effective sham controls to limit bias may be difficult. We recommend 
113 using the Q-submission Program to discuss alternative approaches to provide unbiased outcomes.
B. Recording Medication Use
114
115 Pivotal OUD device studies should record all baseline medications including those used for 
116 treating OUDprior to initiating treatment intervention with an investigational device. 
117 Investigators should recordeach drug, the dose, the duration of use, changes in dose, and starting 
118 or stopping a drug after participation in the study begins. Adherence to OUD and other SUD 
119 treatment medications may be assessed with participant diaries, using pill counts, and random or 
120 regularly scheduledtoxicology drug screeningfor prescribed and non-prescribed drug use, 
121 among other methods.
C. Monitoring Prescribed and Nonprescribed Drug Use 
122 
123  Appropriate monitoring of prescribed and non-prescribed drugs is integral to a pivotal OUD 
124  device study design. Without appropriate drug screening measures or objective methods of 
125 verifying opioid use, the clinical meaning of any demonstrated benefit of the device is unclear.
126  False or inaccurate results can occur in self-reported outcome measures of opioid use. For this 
127 reason, pivotal OUD device studies should measure opioid usage with both participant self-
9 Available at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/requests-feedback-and-
meetings-medical-device-submissions-q-submission-program. 
10 CDRH encourages sponsors to include in studies of devices intended to treat OUD a diverse population that is 
representative of the United States population living with OUD.
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128  reports and objective verification measures. Testing for non-prescribed drugs may be useful in 
129 some studies.
130
131  Typical objective measures to corroborate participant self-reports are random and scheduled 
132  urine tests using validated toxicology assays at times consistent with relevant drug 
133  pharmacokinetics. Other drug screening options include measuring drug levels in blood or saliva, 
134  and the use of validated drug detection technologies as they become available. A positive 
135  toxicology result that is confirmed by a quantitative reference method (e.g., liquid 
136  chromatography with tandem mass spectrometry) should take precedence over self-reported 
137 abstinence since the last negative result. 
D.  Appropriate Study Length and Evaluation
138
139  The duration of a clinical study is important to consider. CDRH recommends that OUD device 
140  studies have a length that is clinically significant and well justified. Pivotal OUD device studies 
141  with a minimum treatment duration of 6 months are recommended. Appropriate study duration is 
142  necessary because OUD is a condition with a high rate of relapse, and brief intervals of 
143  modification of drug use are unlikely to confer significant clinical benefit. It is essential that, for 
144  an indication for OUD treatment, investigators consider the durability of the effects of the device 
145  and acknowledge any uncertainty about the benefits and risks. Because of the importance of a 
146  long study duration, the protocol should include a detailed description of effective procedures for 
147  retaining study participants, risk-based ongoing data management, and procedures for obtaining 
148  primary outcome information that is missing while it is still available to be retrieved as further 
149 discussed in sections IV.E and IV.F. 
E.  Participant Retention and Preventing Missing Data
150
151  During the design of a pivotal OUD device study, considerable effort should be made to 
152  maximize participant retention and reduce missing data by ensuring adherence to treatment plans 
153  and follow-up schedules. This aspect of research in pivotal OUD device studies may necessitate 
154  new methods. If participants do not adhere to the treatment and follow-up plan, the primary 
155  outcome may not be obtainable, which would weaken the credibility of the intention to treat 
156  analysis. Because the methods of retention may affect the study outcomes, FDA recommends 
157  ensuring adequate blinding of the treatment assignment to minimize decisions to drop out. High 
158  rates of missing data have been major contributors to OUD study failure. Therefore, protocols 
159 should anticipate this problem and provide procedures to prevent it. 
160  Sponsors should acknowledge that missing data typically does not occur at random and use 
161  conservative estimates for missing data when analyzing study results. If the proportion of 
162  missing data is not much less than the difference in response rates, there will be significant 
163  uncertainty in the study results. Methods to account for missing data should be prespecified in 
164  full detail in the statistical analysis plan before the study starts. Even if prespecified, these 
165  methods are accompanied by a large amount of uncertainty when missing data exceeds more 
166  than a few percent. The protocol should ensure that investigators have the resources and a 
167  powerful strategy to detect and correct missing data while allowing flexibility and adaptive 
168  procedures to reduce loss of critical data. Each case of missing data may require a different 
169 solution. Data management should be proactive in early detection of critical missing data at a 
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170 time when it may still be retrievable and reliable. It is also helpful to minimize the amount of 
171 data to be collectedto reduce the workload on investigators so they can concentrate on the most 
172 critical data.
173 Missing data can include adverse events.Access to clinic, hospital, and pharmacy records can 
174 provide more accurate information than participantreports. Adverse life changes are also 
175 potential adverse events that should be assessed and recorded.
F. Clinical Outcomes
176
177 Clinical outcomes that provide valid scientific evidence of clinically significant benefits
178 provided by the device are essential to support OUD treatment indications.11 For the purposes of 
179 this guidance, FDA considers a clinically significant benefit to be an improvement in how a 
180 study participant feels, functions, or survives,such as a reduction in hospitalizations,or 
181 improvements in daily life including the ability to resume work, school, and other activities.12
182  When choosing primary outcomes for pivotal OUD device studies, sponsors should identify the 
183  clinical objectives of the device for the target patient population and align the objectives with the 
184  desired indications for use, a relevant definition of a clinically significant benefit, and the choice 
185  of effectiveness outcomes. FDA recommends the inclusion of secondary outcomes that measure 
186  different manifestations of OUD to support the robustness of any evidence of demonstrated 
187  clinically significant difference in the primary outcome. The presentation of a consistent and 
188  clinically significant difference across an array of outcomes can contribute to the evidence 
189 needed to support a marketing submission.
190
191  Secondary outcomes are intended to support the primary outcome and generally cannot stand 
192  alone. To the extent possible, secondary outcomes should be limited in number and should be 
193  minimally burdensome to participants and investigators to enhance retention and prevent missing 
194  data. See section IV.E on missing data. If the primary outcome measure shows how a participant 
195  feels, functions, or survives, well-chosen secondary outcomes can provide evidence that 
196 confirms or explains the observed effect.
197
198  FDA recommends that sponsors select study outcomes that are relevant to the population, the 
199  indication, and the clinical situation. The outcomes discussed below are recommended primary 
200  or secondary outcomes that can be considered for use in a pivotal OUD device study. The list 
201  provided below is not exhaustive. FDA does not recommend choosing all the listed outcome 
202  measures for any given study and recognizes that there may be other outcomes that would be 
203 appropriate to a specific study that are not listed below.
11 To provide consistency across OUD treatment trials, the recommendations in this section are consistent with the 
guidance entitled Opioid Use Disorder: Endpoints for Demonstrating Effectiveness of Drugs for Treatment 
Guidance for Industry, U.S. Department of Health and Human Services Food and Drug Administration Center for 
Drug Evaluation and Research (CDER) October 2020, available at https://www.fda.gov/regulatory-
information/search-fda-guidance-documents/opioid-use-disorder-endpoints-demonstrating-effectiveness-drugs-
treatment-guidance-industry. 
12 Alan E. Kazdin, The Meanings and Measurement of Clinical Significance. Journal of Consulting and Clinical 
Psychology, June 1999, Volume 67, No. 3, pages 332-339.
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204 (1)  Change in Drug Use Pattern13
205 FDA generally accepts a positive change in drug use patterns as a surrogate for the benefits of 
206 abstaining from drug taking or for the presumed benefits of reducing drug taking. A reduction in 
207  drug-taking behavior has been used as a surrogate outcome for the benefit of abstinence14 or 
208  presumed benefit of reducing drug taking in many investigations, including those used to 
209  evaluate drug products for the treatment of OUD.  
210   
211  If using change in drug use pattern as an outcome, FDA recommends that sponsors compare 
212  percentages of responders rather than group means. For example, a responder could be defined as 
213  a participant who reduces the use of opioids to an amount associated with a clinically significant 
214  benefit. In general, the threshold may vary according to study design. Thresholds may not be 
215  transferable from study to study because of differences in the populations, treatments, risks, 
216 benefits, uncertainties in study results, and methods of analysis. FDA recommends asponsor 
217 provide a rationale for how their response threshold will improve the lives of those with OUD.
218 For example, studies of devices for usewith prescribed medication-assisted treatments for OUD 
219 should demonstrate clinically significant improvement compared to agroup not receiving active 
220 device treatment and receiving the same protocol-defined medication-assisted treatment.
221
222 Sponsors should consider the treatment goals of their device when defining a responder. 
223 Abstinence can be used to define a treatment responder. To demonstrate a complete abstinence 
224 response, pivotal OUD device studies should be designed with frequent measurements of drug 
225 use to reduce uncertainty about the true magnitude of the treatment effect. 
226
227 Drug use changes short of abstinence may be considered when evaluating clinically meaningful 
228 responses to OUD treatment. When proposing other drug use patterns to define a clinically 
229 meaningful response, sponsors should explain how the change in drug use pattern will be 
230 measured and verified objectively and submit valid scientific evidence showing that such a 
231 reduction in drug use is clinically significant, with evidence of improvements in physical, social, 
232 cognitive,and emotional function in their lives.
233  (2)  Change in OUD Disease Status Using DSM-5-TR Diagnostic 
234 Criteria
235  Diagnostic criteria for OUD encompass drug use and its effect on health and well-being. For 
236 devices intended to treat OUD, an appropriate outcome may be a clinically significant change in 
13 Drug use pattern refers to the frequency, timing, quantity, and intensity (uses per day or amount per use) of 
problematic drug use by an individual patient. From a practical standpoint, several of these parameters are infeasible 
to measure, and the most commonly used parameter is days of use. The phrase change in drug use pattern is used 
to emphasize that individual patient responses are of interest. See page 4 of Opioid Use Disorder: Endpoints for 
Demonstrating Effectiveness of Drugs for Treatment Guidance for Industry, U.S. Department of Health and Human 
Services Food and Drug Administration Center for Drug Evaluation and Research (CDER) October 2020, available 
at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/opioid-use-disorder-endpoints-
demonstrating-effectiveness-drugs-treatment-guidance-industry. 
14 Abstinence refers to zero days of use within an assessment window. The more general phrase reduction in drug 
use is subject to many interpretations, including reduction of group means on quantity or frequency of problematic 
drug use with no single individual having an improvement in their OUD. See id.
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237 disease severity related to the clinical diagnosis of OUD. We recommend that, if all study 
238 participants meet the DSM-5-TR criteria for moderate-severe OUD at baseline,15 sponsors could 
239 use the proportion of participants meeting DSM-5-TR criteria for remission of OUD at the end of 
240 the study as a primary or secondary effectivenessoutcome.When designing a study to determine 
241 safety and effectiveness, a sponsor should ensure the clinical diagnosis method or scale is 
242 appropriate to support the proposed indication. In apivotal OUDdevice study, the clinical 
243 evidence should demonstrate a clinically significant change in disease status or duration of OUD.
244 (3) Reduction in Adverse Outcomes of OUD
245 FDA encourages sponsors to design clinical studies that evaluate the reduction of clinically 
246 significant adverse outcomes related to OUD. Examples of clinically significant adverse 
247 outcomes related to OUD include:
248  The need for emergency intervention;
249  Hepatitis C virus infection or reinfection; and
250  Mortality (overall mortality or overdose-induced mortality).
251
252 Use of other adverse outcomes may be appropriate when there is clear clinical significance 
253 associated with a reduction in that adverse outcome as it relates to the treatment of OUD. 
254 However, not all adverse outcomes are inherently clinically significant for treating OUD. 
255 Sponsors can propose other adverse outcomes than those listed, and can study several outcomes
256 in the same study, selecting one as the primary outcome, and selecting one or more as secondary 
257 outcomes or a composite of adverse outcomes. Consideration for the sample size and study
258 duration can be informed by the rate of adverse outcomes of interest in the population being 
259 studied.
260 (4) Patient-Reported Outcome Instruments
261 Patient-reported outcome (PRO) instruments with established clinical significance may provide 
262 information to help evaluate how a patient feels or functions. When designing a study using PRO 
263 instruments, sponsors should consider the magnitude and duration of change in the PRO that 
264 represents a clinically significant benefit. Sponsors can develop PROinstruments to evaluate 
265 concerning symptoms and experiences associated with OUD that effect how a patient feels or 
266 functions in daily life. When selecting or developing a PROinstrument, sponsors should follow
267 principles outlined in the FDA guidances, Patient-Reported Outcome Measures: Use in Medical 
268 Product Development to Support Labeling Claims16 and Principles for Selecting, Developing, 
269 Modifying, and Adapting Patient-Reported Outcome Instruments for Use in Medical Device 
270 Evaluation.17
15 Specific criteria are in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5-TR), 
F11.10 through F11.21.
16 Available at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/patient-reported-
outcome-measures-use-medical-product-development-support-labeling-claims.
17 Available at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/principles-selecting-
developing-modifying-and-adapting-patient-reported-outcome-instruments-use. 
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271 (5)  Other Outcome Measures
272  FDA encourages sponsors to consider other outcome measures that might help demonstrate the 
273  clinical benefit of devices intended to treat OUD. For example, a reduction in hospitalizations for 
274  OUD or improvements in a participants ability to resume work, school or other positive social 
275  activity. If available, such data may be significant to both participants and clinicians and are 
276  highly valuable because they represent the benefits that are significant to participants, their 
277  families and caregivers; namely evidence of a real, durable improvement in how the participant 
278  functions in daily life. A complementary clinicians assessment corresponding to each patient-
279  reported outcome during the study can provide additional information that is helpful when 
280  making a benefit-risk determination. Additional outcomes measuring treatment retention and 
281  measures of participant satisfaction with treatment accompanied by evidence of a clinically 
282  significant improvement in function in daily life caused by the device, may be included as 
283 supportive secondary outcome measures.
284
285
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