Patient- and clinician-rated outcomes were keys in supporting labeling claims.
Regulatory agencies are increasingly using data collected from clinical outcome assessments (COAs) to evaluate drugs for approval, and sponsors are increasingly using these data successfully to support drug-labeling claims.
COAs measure a patient’s symptoms and mental state, as well as the effects of their disease or condition and level of functioning. Four types of COAs are available, based on patient-reported outcomes, clinician-reported outcomes, independent observer-reported outcomes, or measuring performance outcomes.
Mapi Research Trust, a non-profit organization that provides COAs for medical research, presented a case study on the use of COA data to evaluate medications for restless legs syndrome (RLS) during a poster session at the 21st International Congress of Parkinson’s Disease and Movement Disorders in Vancouver, BC.
Catherine Acquadro, MD, (pictured) an expert in evaluating patient-reported outcomes and a scientific advisor at Mapi, led the study team.
To conduct the study, the Mapi team explored the websites of the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA) to identify all medicines approved for the treatment of RLS, a movement disorder marked by an irresistible urge to move the legs, owing to unpleasant sensations in them when they are at rest.
Their objective was to determine how regulatory agencies use COAs in the drug-approval process. The team also used their proprietary PROLABELS database and ePROVIDE platform to identify labeling claims and review them for endpoint positioning.
The Mapi team found that the EMA and FDA together approved 9 products with an indication for the treatment of RLS. The 4 products approved by the FDA include gabapentin (Horizant/Xenoport), pramipexole (Mirapex/Boehringer Ingelheim), ropinirole (Requip/GlaxoSmithKline), and rotigotine (Neupro/UCB).
The 5 products approved by the EMA include 3 types of pramipexole (generic pramipexole/Accord, Mirapexin/ Boehringer Ingelheim, and Sifrol/ Boehringer Ingelheim) and 2 brands of rotigotine (Leganto/UCB, Neupro/UCB).
For the products approved by both agencies — pramipexole (Mirapex or Mirapexin) and rotigotine (Neupro) — the sponsors submitted the same data to the regulators for approval. The agencies evaluated all products by using the same patient-related outcome measure, the International Restless Legs Syndrome Study Group Rating Scale (IRLS), which assesses the severity of the disease.
Using this scale, the patient scores his or her symptoms in 10 categories, including severity of RLS in the legs and arms as well as global severity, urge to move, relief by walking, sleep disturbance, daytime fatigue and somnolence, frequency and average daily severity of symptoms, and their impact on daily activities or mood.
Scores for each item range from 0-4 (not present to severe) and are then summed for all 10 items to calculate a total score ranging from 0-40 (not present to maximum severity of all symptoms).
The sponsors made the same claim for all products: improvement in IRLS score from baseline values. Two co-primary efficacy endpoints based on COAs were used: mean change from baseline in IRLS, and Clinical Global Impression of Improvement or Clinical Global Impression of Illness Severity.
“The patient’s perspective is of paramount importance in the evaluation of medicines approved for RLS,” the Mapi team noted in their findings. However, they concluded that clinician input was another valuable endpoint because all evaluations were based on the use of both patient-rated outcomes and clinician-rated outcomes.
“The FDA and EMA have both accepted patient self-rated outcomes data for RLS,” noted study co-author Marie-Pierre Emery, a senior author relations specialist in the Author Collaboration Unit at Mapi Research Trust in Lyon, France. “It’s not enough to simply focus on objective biological measures,” Emery said. “Researchers must also focus on the patient’s perspective on their illness and its response to treatment.”
“There has been a growing trend toward accepting self-rated outcomes data,” Emery added. “It’s an important measure of a drug’s effects on quality of life, and RLS really affects quality of life. For example, RLS really affects sleep and may require sleep medications.”