RiskMAP development and assessments required by the Best Pharmaceuticals for Children Act (FDA and CDER, 2005).
Safety officers begin the process of building on initial reports either when requested by an OND reviewer to pursue a signal or on the basis of their own review of reports. Initial safety signal information is generally incomplete or uncertain; for example, a case report has few details, a patient is taking several drugs at once and a reaction could be related to the combination or to one of the drugs alone, could be related to the disease rather than to any of the drugs, or the effect may be so common in the population that it is difficult to determine whether it is associated with drug use. Only through additional investigations—including data mining searching with MedDRA codes, review of premarket studies, and analysis of available data from sources described above—might a picture begin to emerge. Increasingly, ODS/OSE is undertaking assessments not just regarding the drug that may have generated reports but regarding the class of drugs that it belongs to.
Rare is the story that builds as clearly and completely as one would like for making scientific evaluations and regulatory decisions. Adequate information to quantify risk or to compare the safety of a drug with the safety of alternative therapies in its class may not be readily available. Not uncommonly, uncertainties and professional disagreements about the significance of signals persist.
OND and ODS/OSE are expected to work together to assess risk and determine how to manage it, but OND has authority to make regulatory decisions related to the findings. A recent Government Accountability Office report noted problems in the relationship between ODS/OSE and OND staff, including lack of clarity about roles and responsibilities and communication barriers (GAO, 2006). As noted earlier, FDA’s official response to those findings cited its commitment to making ODS/OSE and OND “co-equal partners in the post-market identification and timely resolution of drug safety issues” (GAO, 2006) (see discussion in Chapter 3).
Another challenge facing FDA is to decide when to alert the public and providers of AE reports that are under investigation. On one hand, reporting at the earliest stages could confuse and perhaps unduly alarm patients and providers and lead patients to inappropriately avoid or stop using a drug that they need. On the other hand, waiting too long to alert providers and users about potentially serious problems with a marketed drug can put patients at risk. FDA has been criticized for waiting too long and has proposed a Drug Watch Web site that would give the public and providers information about potential problems with marketed drugs earlier than in the past. The proposed Drug Watch program has been subject to criticism from the pharmaceutical industry. One reason given by industry against the program is that it is not useful to look at one study in isolation, as would be