Facts and Figures: Assessing the Risks

Assessing the Risks of Prescription Medicines: The 411

Since 2008, the FDA has used REMS as a tool so the benefits of needed medicines outweigh the risks of taking them. But how does FDA determine the risks of a prescription drug in the first place?

The answer has to do with how FDA weighs the known benefits of a medication against known risks and the potential – and possibly unknown – risks. For medicines not yet approved, FDA makes this determination by evaluating the scientific evidence from a series of large clinical studies in humans conducted by the drug’s sponsor and summarized in the company’s New Drug Application (NDA).  In fact, demonstrating that the medicine’s benefits outweigh its known risks for its proposed use is the necessary criterion for FDA to approve the drug.

What Is a Serious Risk?

Regarding the use of prescription medicines, FDA defines a “serious risk” as one that results in or places the patient in danger of death, hospitalization, incapacitation or disruption of the ability to conduct normal life function, congenital anomaly, or a birth defect

However, a number of factors are involved in how FDA determines the benefits and risks of a medicine. As it applies to the benefits, FDA considers:

  • The specific benefits to patients – such as improving a patient’s quality of life, reducing the probability of death, improving patient function, reducing the probability of loss of function, and providing relief from symptoms
  • The magnitude of the benefits – the extent of the positive changes in the condition and improvements for specific types of benefits
  • The probability of experiencing one or more benefits from taking the medicine – this means determining whether the drug’s benefits occur frequently in the patient population or only in a small number of patients and if some patients experience different benefits or different levels of the same benefit
  • The duration of the effects – how long the benefit can be expected to last for the patient

Similarly, FDA considers a range factors to determine the probable risks of a medicine. These include:

  • The severity, types, numbers and rates of the harmful events associated with the use of the drug or biologic – this involves both non-serious events and events that can cause serious complications, illness or death
  • The probability of a harmful event – based on determining the extent of the patient population that is expected to experience a harmful event
  • The duration of the harmful event(s) – such as how long the adverse consequences last and whether the medicine can cause reversible or permanent harm
  • The severity of the disease or condition – which is especially important for patients living with a very severe disease who are more likely to be willing to accept more risk from their treatment
  • The availability of alternative treatments – this factor is also important if there are few or no other treatment options available to patients and involves FDA’s judgement that patients may be willing to accept more risk, even for a small amount of benefit
  • The potential for risk mitigation – the determination that warnings, precautions and a REMS system will minimize the potential for a harmful event from occurring

Once a drug is marketed and new information about an unexpected drug-related health risk is detected, FDA applies the same risk factors to ensure the medicine can continue to be used safely. Based upon this assessment, FDA can take a number of steps to manage the new risks, including:

  • Requiring the manufacturer to add new information about the safety concern to the drug’s label
  • Issuing a Public Health Advisory that highlights important safety information about the drug along with recommendations to manage the risks
  • Issuing an Alert to healthcare professionals to highlight important new information in the drug’s labeling
  • Posting a Patient Information Sheet on the FDA website that explains the safety concern and encourages patients to talk to their healthcare provider for further information. These Information Sheets can be found on the FDA’s Index to Drug-Specific Information, currently at https://www.fda.gov/drugs/postmarket-drug-safety-information-patients-and-providers/index-drug-specific-information
  • Requiring the manufacturer to design and implement a REMS program
  • Requiring the manufacturer to conduct postmarketing studies to evaluate signs of a serious risk related to a drug and to submit the findings to FDA. After assessing these new findings, FDA may require additional safety precautions.

The final safeguard to the public is FDA’s decision to remove an approved drug from the market.  In these situations, FDA makes the judgement that the medicine’s serious safety risks cannot be managed effectively and therefore, the risks outweigh any benefits the drug provides. These decisions are based on the weight on the scientific evidence and underscore FDA’s important role in addressing serious unexpected adverse events and taking definitive action when needed.