Leveraging the data

From a regulatory point of view, the data can be enormously valuable in offering insight into the safety profile of the product outside the controlled environment of a clinical trial. In terms of planning for risk management post-launch, data from a MAP represents a bridge between the controlled, monitored environment of the clinical trial and the real-world usage patterns with commercial availability. In the 2009 preamble to the updated FDA rules on expanded access programs, the agency acknowledged the usefulness of data collected in support of an NDA, both from a safety and efficacy perspective.

In a review of 49 orphan drugs approved in the European Union between 2005 and August 2012, seven (14 percent) of the applications included safety data derived from a compassionate use program. In three cases information from the program was included in the safety sections of the approved summary of product characteristics (SmPC). In the case of Laboratoires Biocodex's Diacomit, an anti-epileptic approved in 2007 for the treatment of a rare, severe form of epilepsy in young children, the data from the French compassionate use program was quoted in the SmPC to provide some guidance to physicians on use of the product in children who were younger than those included in the main trial.

Genzyme's Mozobil (plerixafor) received approval from FDA in 2008, and EMA in 2009, to enhance mobilization of hematopoietic stem cells in patients with lymphoma and multiple myeloma. Registration trials had excluded patients who had failed to mobilize adequate numbers of peripheral blood stem cells via traditional approaches. A compassionate use program was initiated in 2008 in the European Union for these patients.

Among patients at risk to mobilize poorly, the subgroup most difficult to treat are those who have already failed mobilization attempts. A review of the compassionate use data revealed that approximately 75 percent of the patients who are hardest to mobilize were successfully rescued after one or more previous failures.

Similarly, a retrospective study of over 70 patients enrolled in a named patient program was used to assess the real-world clinical benefits of Celgene's Vidaza (azacitidine), for treatment of patients with lower risk myelodysplastic syndrome (MDS). Trial data demonstrated that Vidaza induces a significant survival advantage in patients with higher risk MDS. The trials however, included only a small number of patients with lower-risk disease. Data from lower-risk patients enrolled in the named patient program indicated that Vidaza may be a good therapeutic option for these patients. The study's authors conclude that:

"These observations represent real-world data, because patients were treated outside of the setting of a clinical trial, in which strict inclusion and exclusion criteria may have limited the generalizability of the findings."

Data derived from MAPs can also be used to create a more patient-focused approach to treatment. A study published last year in the British Journal of Urology International uses data from expanded access programs conducted in the United States and Europe, along with clinical experience, to help guide optimal use of several drugs for renal cell carcinoma. The authors noted that populations recruited for randomized clinical trials can under-represent patient subtypes, which can impact the clinician's ability to select the most appropriate agent for a particular patient. A retrospective analysis of MAP data yielded important insights into treatment of what the authors describe as "emerging" and "minority" patient subgroups.

Data collected during a MAP can also provide strategic insight to support internal decision making and planning. Companies can learn about demand levels by geography, key prescribing centers, treatment pathways, and off-label use by country. This sort of information, although not conclusive, can offer valuable insight to multiple departments within pharmaceutical organizations. The relevance of the information stretches beyond the medical and clinical departments and could extend to health economics and outcomes research.

When considering options for such data collection, a few best practices will help optimize efforts:
» Understand the normal treatment practice so data collection works in concert with physicians.
» Define your objectives for the data. Identify those areas in which you are seeking to gain greater insight and let that guide what data is collected. Be cognizant of the burden the data collection may put on the physician and refine accordingly.
» In some countries such as the United States, France, and Germany, there is a regulatory agency review of the protocol one intends to use for a MAP. If a company wants to collect data in any organized fashion and use it, putting a protocol in place is advisable, regardless of whether it's required by the national regulatory agency.

Sue Barrowcliffe is Global Director, Regulatory and Medical Strategy at Idis. She can be reached at sbarrowcliffe@idispharma.com
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