Every day, thousands of consumers suffer all kind of injuries unexpectedly caused by the medications they need to take. Patients and doctors need to trust the regulatory agencies of their respective countries whose role is to assess the various drugs’ safety before these are released to the public. Before a new molecule is approved for use, the U.S. Food and Drug Administration (FDA) or the European Medicines Agency (EMA) require it to be extensively tested in complicated clinical trials which often require several years.

However, pharmacology is a complex science, and even the largest study will always fail to properly recognize the myriad of challenges faced by regulators to assess a medication’s dangerousness. Despite the robust approval process and comprehensive premarket review system, many side effects are often unexpectedly discovered during the postmarketing period.

No lab research may, in fact, adequately predict all the possible variations that often happen in real-world settings, such as the harmful interactions with other medicines or substances. Even the largest clinical trial will always include a relatively narrow spectrum of individuals, leaving many different patient populations (such as pregnant women, children or the elderly) untested until the drug reaches the general public.

The EMA and the FDA still rely on their public adverse events reports and pharmacovigilance systems to adequately protect the public from all the unexpected dangers of a new drug. Other than just spontaneous reporting, published case reports and cohort studies also represent other potential sources of alert signals that may warn the scientific community about a medication’s unforeseen danger.

Recalls, warnings and pharmacovigilance

Millions of adverse drug reaction reports are submitted by doctor and patients worldwide, forcing the regulators to ask the pharmaceutical companies to help them in their pharmacovigilance efforts.The manufacturers may often recognize unidentified medications’ risks in a much more timely fashion since they possess better resources and a reliable “in-house” knowledge of their own branded products.

Whenever a new harmful effect is correctly identified, the FDA’s responsibility is to protect the public by warning patients and doctors about the risk. This is usually done by updating the medication’s label with all the new information pertaining the alleged hazard in words that could be easily understood by consumers.

The “black box warning” is the name of an explicitly boxed warning added to many medications’ labels by the American federal regulator in order to draw the public’s attention to the most threatening health risks. Although the adverse impact of under-warning may be obvious, even over-warning is a process not devoid of negative consequences. Many depressed patients’ lives have been put a risk, for example, when the addition of several warning on mood stabilizers led to massive undertreatment.

If a warning is not enough, however, and the use of a drug may reasonably expose a subject to life-threatening consequences or serious side effects, the FDA often took action by issuing a product recall. In some instances, even manufacturers may opt to remove their product from the market by their own will.

The consequences of a defective drug

The Big Pharma need to invest significant financial resources in testing and perfection a new medication before regulators approve it. Tens of thousands of patients must be enlisted and observed for at least two years to provide a clinical trial with enough power to detect a drug’s risk on the long-term reliably. The cost of these researches may easily reach millions of dollars, and failure is often not an option for the largest pharmaceutical manufacturers.

Because of that, the FDA is often put under a lot of pressure, especially when the federal regulators opt to request new post-marketing studies or, even worse, need to recall a defective product. Frequently, the choice of not recalling a dangerous substance from the market or not warning the public about its hazards, is justified by the urge to provide a treatment to the most severely ill patients still. However, waiting to obtain further medical evidence that proves its dangerousness may expose the general public to catastrophic risks.

For example, the FDA received much criticism when, in the early 2000s, it decided not to add a cardiovascular warning to the label of Vioxx (rofecoxib). The agency concluded that the results of the APPROVe study did not provide compelling evidence that the infamous nonsteroidal anti-inflammatory drug (NSAID) was linked with fatal cardiovascular side effects. Although, later in 2004, Merck decided to voluntarily recall the product from the market, at least 38,000 victims were already dead because of the effects of the new medication.

The manufacturers’ responsibility

The Vioxx scandal was neither the first nor the last time a pharmaceutical company aggressively strong-armed the approval of a dangerous drug. A controversy arose about the possibility of an unhealthy relationship between the FDA and Merck since many federal regulators shared a common background as consultants for the Big Pharma.

More often than not, a medicines’ safety and benefits are unscrupulously overstated to increase its sales through deceptive advertisement tactics. On top of that, health care providers are frequently seduced into prescribing certain medications with abhorrent kickback schemes that include luxurious trips and lavish entertainment.

A few years ago, the U.S. Department of Justice accused Daiichi Sankyo of bribing physicians to fraudulently prescribe several antihypertensive drugs such as Azor and Benicar. The company eventually opted to pay $39 million to settle down the accusations in January 2015.

Giants of the pharmaceutical industry such as Johnson & Johnson were found guilty of off-label promoting medications such as Risperdal, Invega and Natrecor for indications for which they never received FDA’s approval. Not only the off-label promotion of drugs exposes whole populations of patients to unexpected risks, but there’s often no clinical evidence that proves that these medications are effective for their use since no adequate research has been done yet.


Dr. Claudio Butticè, Pharm.D., is a clinical and hospital pharmacist who worked for several large public hospitals in Southern Italy, as well as for the humanitarian NGO Emergency. He is an accomplished medical writer who wrote as an author in several encyclopedias, including The SAGE Encyclopedia of Cancer and Society (2015), The SAGE Encyclopedia of World Poverty (2015), ABC-CLIO Encyclopedia of Science and Technology (in press), and other sociology and anthropology reference textbooks. He’s also a medical writer and journalist who wrote for online magazines such as The Ring Of Fire, Digital Journal, Business Insider and Techopedia. Dr. Butticè holds a Master’s degree in Pharmacy from the University of Palermo.