Opioid use disorder: FDA drafts guidance on clinical considerations for devices
Regulatory News | 27 July 2023 |
Sponsors of clinical trials of medical devices to treat opioid use disorder (OUD) face “complex challenges,” the US Food and Drug Administration (FDA) said. In a draft guidance issued on Thursday, the agency stressed that sponsors should consider the makeup of the treatment population, the accuracy of self-reported outcome measures and other factors that could impact clinical development of such devices.
Other challenges include high rates of missing data, the confounding effects of concomitant drug treatments and measuring the durability of the treatment effect of an investigational device.
To address these challenges, FDA said that OUD device studies should have a well-defined study population, appropriately monitor drug use and control for biases. They should also include an appropriate follow-up period, study participant retention plans and data analysis plans.
"We are committed to helping industry develop solutions that are proven to be effective to address the devastation caused by the overdose crisis,” said FDA Commissioner Robert Califf. “This draft guidance for device studies should prompt industry to collect more comprehensive, timely and diverse data to support device submissions that may help improve the lives of those with opioid use disorder."
FDA acknowledged the challenges with study methodology in developing OUD treatments and encouraged sponsors to develop alternative methodologies to address them. It said it is also open to alternative methodological approaches in certain circumstances and recommended sponsors discuss them with regulators early on through the Q-submission process.
The guidance points out that it is important to accurately represent the intended treatment population by defining specific inclusion and exclusion criteria so prescribers can be confident in the effectiveness of the OUD device. It adds that none of the participants, treating investigators or evaluators should be aware of a participant’s treatment assignment in the clinical trial.
To ensure patient medication use is properly recorded during the clinical trial, FDA said investigators should record each drug, its dose, duration of use, changes in dose and starting or stopping a drug after participation in the study begins. The agency also notes that OUD treatment adherence can be assessed by asking participants to keep a diary, using pill counters and administering toxicology screenings.
FDA also wants sponsors to track prescribed and non-prescribed drug use during the clinical trial.
“Appropriate monitoring of prescribed and non-prescribed drugs is integral to a pivotal OUD device study design,” said FDA. “Without appropriate drug screening measures or objective methods of verifying opioid use, the clinical meaning of any demonstrated benefit of the device is unclear.”
“False or inaccurate results can occur in self-reported outcome measures of opioid use,” the agency added. “For this reason, pivotal OUD device studies should measure opioid usage with both participant self-reports and objective verification measures. Testing for non-prescribed drugs may be useful in some studies.”
FDA said the duration of OUD device clinical trials needs to be significant and justified by the sponsors. It recommends that the treatment duration of the trials be at least six months long.
“Appropriate study duration is necessary because OUD is a condition with a high rate of relapse, and brief intervals of modification of drug use are unlikely to confer significant clinical benefit,” said FDA. “It is essential that, for an indication for OUD treatment, investigators consider the durability of the effects of the device and acknowledge any uncertainty about the benefits and risks.”
The guidance makes recommendations on several other key areas, including how to retain study participants, prevent missing data and record study outcome information.
FDA noted that early feasibility studies and other preliminary studies are outside the scope of the guidance, as are diagnostic tests for the detection of opioid use, devices intended to diagnose or to help determine the risk of developing OUD, devices intended to treat pain and combination products.
Stakeholders can comment on the draft guidance on www.regulations.gov under docket no. FDA-2023-D-0466 until 25 October.
Statement, draft guidance
Other challenges include high rates of missing data, the confounding effects of concomitant drug treatments and measuring the durability of the treatment effect of an investigational device.
To address these challenges, FDA said that OUD device studies should have a well-defined study population, appropriately monitor drug use and control for biases. They should also include an appropriate follow-up period, study participant retention plans and data analysis plans.
"We are committed to helping industry develop solutions that are proven to be effective to address the devastation caused by the overdose crisis,” said FDA Commissioner Robert Califf. “This draft guidance for device studies should prompt industry to collect more comprehensive, timely and diverse data to support device submissions that may help improve the lives of those with opioid use disorder."
FDA acknowledged the challenges with study methodology in developing OUD treatments and encouraged sponsors to develop alternative methodologies to address them. It said it is also open to alternative methodological approaches in certain circumstances and recommended sponsors discuss them with regulators early on through the Q-submission process.
The guidance points out that it is important to accurately represent the intended treatment population by defining specific inclusion and exclusion criteria so prescribers can be confident in the effectiveness of the OUD device. It adds that none of the participants, treating investigators or evaluators should be aware of a participant’s treatment assignment in the clinical trial.
To ensure patient medication use is properly recorded during the clinical trial, FDA said investigators should record each drug, its dose, duration of use, changes in dose and starting or stopping a drug after participation in the study begins. The agency also notes that OUD treatment adherence can be assessed by asking participants to keep a diary, using pill counters and administering toxicology screenings.
FDA also wants sponsors to track prescribed and non-prescribed drug use during the clinical trial.
“Appropriate monitoring of prescribed and non-prescribed drugs is integral to a pivotal OUD device study design,” said FDA. “Without appropriate drug screening measures or objective methods of verifying opioid use, the clinical meaning of any demonstrated benefit of the device is unclear.”
“False or inaccurate results can occur in self-reported outcome measures of opioid use,” the agency added. “For this reason, pivotal OUD device studies should measure opioid usage with both participant self-reports and objective verification measures. Testing for non-prescribed drugs may be useful in some studies.”
FDA said the duration of OUD device clinical trials needs to be significant and justified by the sponsors. It recommends that the treatment duration of the trials be at least six months long.
“Appropriate study duration is necessary because OUD is a condition with a high rate of relapse, and brief intervals of modification of drug use are unlikely to confer significant clinical benefit,” said FDA. “It is essential that, for an indication for OUD treatment, investigators consider the durability of the effects of the device and acknowledge any uncertainty about the benefits and risks.”
The guidance makes recommendations on several other key areas, including how to retain study participants, prevent missing data and record study outcome information.
FDA noted that early feasibility studies and other preliminary studies are outside the scope of the guidance, as are diagnostic tests for the detection of opioid use, devices intended to diagnose or to help determine the risk of developing OUD, devices intended to treat pain and combination products.
Stakeholders can comment on the draft guidance on www.regulations.gov under docket no. FDA-2023-D-0466 until 25 October.
Statement, draft guidance
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