Many Twists and Turns

The complexity of REMS will definitely place new burdens on doctors, patients, and payers. For example, Amgen's Nplate for chronic adult ITP and GSK's Promacta for low platelet count—two orphan drugs—require the physician to conduct an elaborate procedure of paperwork before prescribing it. This may result in decreased use of the product (and even suboptimal treatment of the patient) in favor of competitor drugs that are easier to prescribe.

The distribution of specialty products through a hospital or physician practice can be easily controlled by means of a REMS. Still, REMS are almost certain to reduce a drug's market size—or at least slow its take-up. Nowhere will this be more evident than in the category of controlled substances and other drugs that have a history of abuse—especially when distributed through retail channels with multiple manufacturers involved. Serious safety issues can also limit access. Adolor's Entereg, which was initially developed for opioid-induced constipation, was believed to have blockbuster potential, but its REMS program has restricted use to short-term inpatient settings. And Adolor has already been slapped with a warning letter from FDA for overstating its drug's efficacy in its promotional material as the company struggles to increase sales.

With the REMS process only two years old, much of its implication remains fluid and unpredictable. It is important that drugmakers work closely with the agency early in the development of a drug to assemble an appropriate REMS program. Equally critical is to watch how the agency's enforcement unfolds.

The "Safety First" Advantage

Yet enhanced regulation of a drug's use by the drugmaker comes with a definite upside. Above all, the effort to evaluate and minimize a product's risk should result, over time, in a significant increase in the safety of all prescription drugs. This, in turn, can only increase public trust in the drug industry. REMS also provides a unique opportunity for a company to enhance the brand value of a product (see figure 3). Designing, implementing, managing, and monitoring an appropriate REMS program can be leveraged by the firm to communicate that "patients comes first when it comes to drug safety."

REMS may improve the probability that FDA will approve a drug, especially an innovative one in an untreated area. To this end, close communication with FDA during the development process about the detection of safety signals and other data should increase the agency's comfort level once the REMS program is in place. As a result, pharmacovigilance and other data-mining techniques that detect safety signals are increasingly critical.

In the post-marketing phase, REMS also improve data collection. Drugs that require registries, distribution tracking, or survey insights on market dynamics provide rich sources of supply-chain information. As the sharing of prescribing data becomes increasingly restricted, a REMS program can lead to superior market intelligence.

REMS can improve access to and interactivity with healthcare providers and patients. Several REMS programs have already been implemented with specific communication plans to assure safe use—doctors and patients need to be registered, trained, and certified first. The drugmaker's deepening involvement in the doctor-patient relationship may increase positive feelings all around. Patient adherence may increase as well.