Protocols need to be simple, and work in real-world settings. While extensive genetic testing is typically conducted during clinical development, detailed and unusual diagnostic work-ups are not palatable for post-approval studies—they're expensive, and most costs of testing are born by participants or their insurers. Long CRFs (case report forms) and burdensome patient-reported outcomes also will not work, since study participation is most often motivated by altruism—lots of bureaucratic paperwork is a big deterrent. Thus, studies need to be streamlined to address focused questions about safety and effectiveness, and practical enough to conduct in the context of real-world medical practices.

The strongest protocols are those that include comparative information about patients diagnosed with the disease of interest and treated with the standard of care. Information on competing products, collected at the same time as the data on the product of interest, will add support for analyses on clinical and cost effectiveness, and provide sound benchmark data, should anecdotal concerns about safety arise.

Make it easy for far-flung, research-naïve sites to participate Studies of rare conditions often mean sponsors must conduct global studies to assemble enough patients. This introduces such issues as multi-national patient protection rules, different patterns of care driven by varying forms of healthcare delivery, and the need to assemble information from providers who don't share a common language.

It is also important to include some "give-backs" to sites to enhance their motivation to participate, such as physician education and practice-enhancement tools, such as notes that can be printed and added to patients' charts. These types of items can be made available as part of the research program.

Value-Added Research

In addition to the very basics of proving clinical and cost effectiveness, and long-term safety, observational studies can help advance understanding about the natural history of disease and treatment practices. The reward is increased visibility in a disease area, which can reinforce corporate image in terms of promoting disease recognition and appropriate management.

Information gleaned from these studies can also feed broader disease registries, which may help to generate additional goodwill among doctors. Disease registries provide a tremendous amount of information and help unite physicians from around the world on the best science and cutting-edge therapies, and offer continuing information that the drug's label doesn't provide. For example, although Cerezyme was approved based on data from relatively few patients, Genzyme has created a registry for Gaucher disease that includes more than 3,000 patients, and allows physicians to learn about a patients' experiences from around the world.

These types of post-approval studies can also direct future efforts because they provide a window into how physicians think about and prescribe the drug. Based on the results, companies may find that physicians need more information and medical education to prescribe the product appropriately. Or, the pharma company may learn about how doctors are prescribing the drug for off-label conditions, which may offer clues to companies about potential new indications. Finally, these resources can provide a wealth of data for a steady stream of publications and presentations at scientific meetings.

The use of practical, streamlined tools, tailored to real-world situations, will help control costs for the small markets and lower budgets associated with developing personalized medicines—and ensure that companies have viable commercial claims for their products. Moreover, by better understanding how their product is used in real-world settings, companies can start asking the next set of questions that will not only ensure that these drugs become a mainstay of modern medicine, but also lead the way toward a more cost-effective healthcare system.