Examples Of FDA Benefit-Risk Analyses
Summaries Of Hypothetical Examples In Guidance
Device Type	Benefits	Risks	Other Factors	Patient Point Of View	Approval Or No Approval?
Implantable device to treat severe, chronic conditions	75% probability of substantial benefit.	3% chance of harmful events; 1% chance of death from surgery.	Unknown mechanism of action. Short trial duration of 1 year.	Most don't mind the 75% risk chance.	Benefits high, patients are tolerant, risks mitigatable: FDA likely to approve.
New device that replaces memory in Alzheimer patients, involves brain surgery, and downloading memories to a computer chip that can later be accessed by patient, but once downloaded, residual memory in patient's brain no longer available	Significant improvement for those in early stages; minimal benefit for those in late stages.	Highly risky surgery: 8% risk of serious adverse events, including paralysis, blindness, loss of motor skills, vertigo.	Small number of those willing to enroll in trial, but data robust.	Very serious effects on quality of life with Alzheimers, no cure for disease. Younger patients likely to tolerate.	Subgroup of patients would benefit. Quality of study data good. Risks high, but may be partially mitigated. No alternative treatments. Allow patients, physicians to decide; FDA likely to approve.
A new breast cancer diagnostic, a serum-based test, can divide patients who show BI-RADS 4 mammogram results into two groups: those for whom biopsy can wait, and those for whom a biopsy is recommended.	Main benefit is avoiding any morbidity associated with an immediate biopsy for the 57% of subjects whose test results indicate low breast cancer probability.	With the test-negative subjects, the observed prevalence of cancer is 1.3%. Main risk is delaying treatment.	Study did not weight the benefit-risk odds for avoiding any biopsy morbidity vs. clinical impact of missing a biopsy detectible cancer.	Patients have low tolerance for delayed diagnosis, treatment for cancer. Must be weighed against need to avoid biopsy-related morbidity.	While benefits and risks defined, weighting of the different kinds of benefits not addressed. FDA would likely take this to an advisory panel.
*New standalone de novo* devicecan give stability to original, more invasive, higher-risk implanted devices, which might otherwise affix themselves with no support.**	With one year of follow-up in a 200-person trial, none of subjects experienced implanted device movement; two experienced device malfunction, a significant improvement over device movement and implanted device performance.	Data suggests that the support device does not increase risk to the patient; poses low-to-moderate risks.	Uncertainty: Results of the trial were limited to one year of follow-up.	Most patients stated they would accept the probable benefits of the device given the probable risks; some patients had complication with the original implanted device, so could benefit from add-on device.	The clinical trial provided assurance of at least one year's effectiveness with device, and it poses no risks that would make it rise to level of a class III device. Special controls can be addressed with testing and labeling. *FDA would likely grant a de novo* request to put it into class II.**
Summaries Of Actual FDA Decisions In Guidance
Device Type	Benefits	Risks	Other Factors	Patient Point Of View	Approval Or No Approval?
Device to treat a very rare cancer in which patients had very little time to life after diagnosis, demonstrated that it performed as well as standard treatment.	Use of the device did not appear to have as harmful effects as the standard of treatment.	There was some uncertainty in the clinical trial as to how well the device performed.	Device caused less severe side effects.	Patients would have access to an equivalent treatment for a deadly disease with less severe side effects.	FDA approved this device.
A permanently implanted cardiovascular monitoring device is intended to diagnose heart failure.	Device study shows it reduces the days patients hospitalized for heart failure by three days.	Implanta- tion procedure for the device requires hospitaliza- tion of two days. Usual surgical risks.	Similar devices on market provide a similar level of benefit, but do not require implantation procedure.	N/A	FDA determined device not approvable, as the benefit of saving one day in hospital did not outweigh the risk.
A permanent birth-control device placed in womens' reproductive systems through vagina with a special catheter, but implant is intended not to be removed.	Device seen as effective in women over a two-year study period; safety data show low incidence of adverse events.	Study results showed several cases where physician could not correctly place device, and device could be fractured, X-ray showed. Explanting would require surgery.	Uncertainty with the long-term impact of the device, and possibility of fracture.	Alternative therapies showed safety and effective- ness for the patient.	FDA deemed the device not approvable for the intended patient population.
Source: FDA guidance, "Factors to Consider When Making Benefit-Risk Determinations in Medical Device Premarket Approval and De Novo Classifications," released Aug. 24, 2016.

Benefit-Risk Calls On PMAs Based On Patient Pluses Versus Adverse-Event Chances, Guidance Says

More from United States

More from North America