By Scott Dixon
May 3, 2010 | In 2007, the U.S. Congress empowered the Food and Drug Administration (FDA) to compel drug manufacturers to adhere to more stringent guidelines to better ensure drug safety. The landmark Food and Drug Administration Amendments Act (FDAAA) requires manufacturers to submit a Risk Evaluation and Mitigation Strategy (REMS) for a drug when it comes to market if the FDA has questions regarding the risks and benefits of the drug (REMS can also be required for drugs already on the market if new information regarding a drug’s safety comes to light).
REMS are risk management plans to help control a known or a potential safety issue of a drug to make certain that the benefits of the product outweigh its risks. REMS can take a variety of forms and are specific to each individual drug risk profile, but some measures may include special requirements for product labeling, marketing restrictions and post-approval surveillance.
These FDA mandates for increased post-approval surveillance have placed greater emphasis on the quality of data gathered in post-market research. Because this research, by its very nature, is not conducted in the closed and highly regulated clinical environments of earlier phase research, the importance of efficiently collecting valuable information directly from patients is paramount. Patient reported outcomes (PRO)—data collected directly from patients—are, therefore, an important aspect of many REMS.
These self-reported measurements combined with the clinical data collected from the health care provider can create a complete view of the patient outcome at baseline, during therapy and after therapy. This 360-degree view of a therapy can provide valuable information on the trial experience, including hard-to-quantify data such as the physical and emotional impact of symptoms and the toxicity of therapies. An understanding of overall treatment satisfaction and effectiveness, as well as the impact of a drug on patients’ day-to-day lives is highly useful for safety measures.
Because late phase trials, however, intrinsically deal with a large number of subjects and are quite lengthy, they can be particularly taxing for study sponsors. Trials are often geographically dispersed with patients and study personnel speaking multiple languages, and maintaining subject enrollment is often difficult, especially if the data collection process is not simple.
Paper-based collection methods are slow and prone to error, and electronic data capture (EDC) solutions developed for investigator site collection do not meet patient requirements. Utilizing electronic PRO (ePRO) technology as part of a REMS offers sponsors a more accurate and cost-effective solution for conducting these large and lengthy studies, and encourages patients to remain involved in the study.
There are several types of ePRO tools, including hand-held PDA devices, but an ePRO solution that harnesses the Internet allows trial participants to enter outcomes data via a Web-browser on computers that they use in their daily lives. This ease-of-use functionality is quite important, as it can encourage continued participation in a trial. If patients are struggling to complete questionnaires and forms, there is a distinct likelihood that they will drop out of the trial, possibly skewing data and negatively impacting study results.
Sponsors also appreciate that there are no dedicated hardware requirements with Web-based ePRO (versus a hand-held PDA approach, for example), which greatly simplifies and speeds up the deployment process and reduces the cost of ongoing maintenance.
Another important advantage of ePRO is that there is an electronic audit trail of when patients enter data, helping ensure that trial protocols are being properly followed. The FDA, as it laid out in recently finalized PRO guidance, wants to ensure that study participants are adhering to trial protocols—meaning if they are supposed to be completing a diary at specific intervals they are complying with that protocol rather than sporadically entering historical data. This traceability requirement recognizes the limitations of paper-based data collection methods.
Improving the safety of drugs and therapies is an over-riding mandate for the pharmaceutical industry. Pharmaceutical and biotechnology companies are constantly looking for better ways to establish a drug’s safety and long-term efficacy while meeting regulatory guidelines. The passage of FDAAA 2007 and its REMS requirements underscores the importance of developing a systemic approach to identifying and analyzing post-market risks. ePRO technology is a significant tool to help organizations better comply with the rigors and complexities of post-market research.
Dixon is vice president of Phase Forward.