prevalent as short time frames and international harmonization are requiring that English be the language of drug safety — at least for 15-day expedited reporting and periodic reporting. Sometimes AEs occurring in a particular country must be reported to the national health authority in the language of that country rather than or in addition to English.
After the report is received or uploaded to the database in a company’s safety department, it must be logged in and a unique number assigned (either before or after a search for duplicate cases). How this is done depends on whether the case arrives electronically or has to be manually entered into the safety database. A rapid determination must be made by a medical professional to see whether it is an “expedited” or “alert” report that must be sent to the health authorities within 15 calendar days of first arrival. The data must be entered into the database (if not already uploaded), coded, medically reviewed, quality-checked, and dispatched outside the company to the appropriate health authorities, subsidiaries, and business partners, as well as to others inside the company such as clinical research physicians who follow the safety profile of the drug in question. Any horrific AEs that might produce immediate regulatory or public health problems must also be identified and acted on urgently.
From a more general point of view, the wisdom of relying on spontaneous reporting of AEs, and thus trusting the goodwill and timely reporting of the healthcare community and patients, has been seriously questioned in the past few years. As several drugs have been withdrawn from the market or have had urgent labeling changes made following the reports of severe toxicity, the search for a more efficient method of rapidly identifying new safety issues is under way in many quarters. The FDA and EU continue to examine its spontaneous reporting system for efficiency and other health agencies around the world are also examining better mechanisms to capture SAEs.
It is highly likely that electronic healthcare records will in time supplant the spontaneous AE reporting systems now in place. With the electronic tracking of all patients’ encounters with the healthcare system (prescriptions given and filled, doctor visits, hospital stays, complaints and diagnoses recorded in standardized forms, etc.), it is likely that health agencies and possibly companies will be able to “mine” the information using complex search algorithms and artificial intelligence tools to do real-time SAE tracking. Prospective use and epidemiology studies will become feasible. Adding genomic data, health economic information, and other data will transform the drug safety surveillance system. This is not likely to happen soon and there will surely be false starts and dead ends in the quest to obtain drug safety data, but there is little doubt that this will occur to everyone’s (presumed) benefit. Note also that the regulations for the handling and reporting of post-marketing AEs are not static in spite of “harmonization”.
Q: Is it really worthwhile reporting another penicillin rash or some other clearly well-described adverse event? Isn’t this a waste of time, money, and resources that could be better used elsewhere?
A: Yes, that is probably true. Known reactions for old drugs in the approved patient populations using the approved formulation, dose, and route of administration do not really add much to the general knowledge of drug safety. It probably is better to use limited resources looking at newer drugs or patient groups where safety is less well characterized.
This is not what most health agencies (officially) say for the understandable reason that, once they ask healthcare professionals and consumers to start making judgments about what is worth reporting and what is not, they begin the slide down the slippery slope. Their reasoning is that it is better to over report, even known AEs on old drugs, than under report and risk missing something. After many years on the market, even old drugs can have new data found on AEs and in particular drug interactions. Whether enough resources will remain available for this remains to be seen.
Q: Does a doctor or other healthcare professional have the right to report a patient’s medical and health information to a private company without the consent of the patient?
A: A good and difficult question. In many jurisdictions (including the US), drug safety reporting by healthcare professionals to companies and the health agency is both legal and encouraged even without the patient’s consent. Disease registries have been in place for decades (e.g., for syphilis) in which physicians and hospitals must report cases to the authorities. In other countries, however, the laws can be complex, and some level of consent may be required, particularly if lab tests, X-rays or scans, or other complementary data are also to be sent. The healthcare professional should check on the requirements and limitations in his or her country. In the EU, a major change in data security and privacy is underway touching all aspects of life, not just drug safety. How this will unfold remains to be seen.
Q: Are consumer reports really worth collecting?
A: Clearly, the information collected from consumers is less useful and less able to be acted on than information healthcare professionals supply. Many reasons account for this: imprecise terminology, lack of complete data, misunderstanding by the patient of complex medical issues, and so forth. This is particularly true for OTC products where there is no healthcare professional intervention in most cases, as the patients self-diagnose and self-treat. Having said all that, useful information can still be obtained that will lead to a signal and further investigation. This is probably not an efficient way to do this, however. In addition, companies handling consumer information, particularly via telephone calls, note that it is time-consuming and requires great diplomatic skills from call center workers. Consumers tend to be more talkative, less precise, and more available than medical personnel who want to report the information and get on to their next patient. Again, it is hoped that electronic health records will make this system obsolete in the future.
CHAPTER
4
The Theory of Drug Safety — Pharmacovigilance
Why does a biopharmaceutical company need a drug safety group? How is a drug safety group constituted? What is the mission of such a drug safety group? A brief history of the US FDA’s safety duties and functions. The FDA’s mission. Pressures on the corporate safety department and the FDA. An overview of the safety functions of government agencies outside the United States.
A century or two ago, the requirements for the safety and efficacy of drug products were either non-existent or poorly defined at best. In 1906, the Pure Food and Drugs Act (FDA) prohibited interstate commerce of mislabeled and adulterated drugs and food within the United States. This covered some safety aspects of drugs but not efficacy. The FDA had, at that time, no jurisdiction or control of efficacy claims made for drugs. In 1912, the law was changed to cover false and fraudulent claims made for drugs. However, the law did not mandate safety and, in effect, unsafe products could be and were marketed. The FDA could not seize unsafe drugs and was limited only to issuing public warnings.
In 1937, a company in the United States marketed elixir of sulfanilamide, which contained diethylene glycol (similar to antifreeze) as a solvent. More than 100 people (including many children) died from this product due to kidney failure caused by the solvent. Because the law did not require safety testing for drugs, the company had done none. As a result of this, the Federal Food, Drug and Cosmetic Act was passed into law in 1938. This law required safety testing to be performed and submitted to the FDA in a New Drug Application (NDA). Additional laws were passed in the 1940s requiring testing for purity, strength, and quality of many drugs.
The next major event was the thalidomide disaster of the early 1960s, when the NDA for thalidomide was valiantly opposed by Dr. Frances Kelsey at the FDA because of insufficient safety information despite strong pressure to approve it.