This blog is as guilty as anyone else including many doctors, patients, and regulators that questions of drug safety boil down to what’s in the pill and what happens in the body. Those two questions are important, if inelegantly expressed.
A recent article points out the other critical aspect of drug safety that is often overlooked – how drugs are perceived and ultimately chosen by users. One element of perceived safety, FDA approval, is (1) mostly misunderstood by consumers and (2) an increasingly fluid concept.
Many consumers hold the belief that FDA approval relates to efficacy or safety in extremes, whereas few had a more accurate picture of FDA approval being granted to drugs proven safe and effective in such a way that any safety risks are outweighed by likely benefits.
As for the fluidity, the author points out that congressional intervention in the approvals process through the user fee program, widely known as PDUFA, has had unintended consequences. This coincides with a greater motivation from industry and agency to speed up the pipeline for new therapies. Vioxx is the case-in-point for such policy’s unintended consequences. After gaining approval, the drug required considerable regulatory attention and post-market surveillance programs in the wake of safety data that was unfortunately generated by a number of injuries caused by the drug.
A federal court permitted an expert who had consulted with defendant Wyeth LLC in 2006 in a case involving the gastric reflux drug Reglan to serve as an expert for plaintiffs bringing a separate case involving the same medication a few years later. The District of Vermont held as it did after finding that there was no confidential relationship between Wyeth and the expert. The plaintiffs in the case, a husband and wife, sued Pfizer, Inc. and its subsidiary, Wyeth, LLC, after the wife became ill with tardive dyskinesia, which the plaintiffs alleged the wife had developed after ingesting Reglan.
A recent study showed that the amount of speaker fees paid by pharmaceutical companies dropped dramatically to nearly one-half of the amount paid in the previous year in Massachusetts. The drop is attributed to the state health department’s collection and publication of data about the amount of speaker fees collected by doctors as well as stricter rules implemented by Harvard University and major medical centers. Harvard Medical School doctors are often targeted by pharmaceutical companies to discuss new therapies because of the value of the university’s brand.
The bans on participating in industry-paid speaking engagements have been instituted in response to the narrowing gap between pharmaceutical companies and researchers. Some speaking engagements are conditioned on the pharmaceutical company’s review and approval of slides and discussion points.
Many view such practices as undermining medicine’s integrity. Critics note that these presentations cause increased prescription of the drugs discussed. Critics also note that some doctors earn upwards of $100,000 per year from speaking, ultimately raising questions as to whether the content of the speeches is intended strictly to benefit patients.
Avastin is mostly known as an anti-cancer drug marketed by Roche. It is often prescribed off-label to treat macular degeneration and other eye-related problems. Avastin’s off-lable use is ascribed to the vast price difference between Avastin and the leading, approved drug for macular degeneration, Lucentis, and the belief that the drugs offer the same safety and efficacy.
Recent cases of blindness and infections in patients who were administered Avastin point to safety concerns in the distribution of the drug. In Florida, twelve patients suffered from eye infections after receiving Avastin injections packaged by a pharmacy into individual single-use syringes. In Los Angeles, five patients at a Veterans Affairs medical center have gone blind in the wake of Avastin injections.
The drug is packaged in a sterile vial that pharmacies sometimes repackage, as was the case in Florida. Roche has held that repackaging the sterile solution leads to the potential for contamination and discouraged the practice.
Pfizer’s Zoloft and Remeron were the subject of a study published in the British medical journal The Lancet.
The study’s authors looked at the efficacy of these drugs in treating depression in patients who suffer from Alzheimer’s disease. The authors concluded that the drugs were no more effective than a placebo. In addition, the authors followed side effects in these patients and found that a greater number of patients taking the drugs, versus the placebo, suffered from nausea, drowsiness, and sedation.
The Supreme Court recently announced its decision in Pliva v. Mensing, where a plaintiff who had taken a generic drug sued the generic manufacturer. Closely watched, the case represents the next step in the developing issue of preemption.
Wyeth v. Levine, decided in 2007, held that federal law and FDA regulations, as far-reaching as they may be, do not displace states’ ability to provide remedies to patients who suffer drug injuries. Pliva v. Mensing on the other hand came out in favor of defendants, holding that a generic manufacturer cannot be liable for a claim that it did not warn plaintiffs of risks so long as the manufacturer complied with relevant federal labeling requirements.
If the two decisions seem to clash, then you are not alone. Justices on the majority and minority made similar observations, emphasizing the incongruity of different results from nearly identical lawsuits. As Justice Sotomayor pointed out, two plaintiffs with similar claims would be treated differently. Drug companies too will be treated differently depending on whether they developed the drug or if they generically manufactured it.
Disparate treatment appeals not only to people’s sense of fairness and justice, but experts have also pointed out the likelihood of shifting costs in the cost of healthcare. Although long called-for, legislative intervention seems likely in response Pliva.
Exelixis Inc. has been testing cabozantinib in clinical trials and recently reported preliminary data on its results. Cabozantinib inhibits processes related to the growth and spread of cancerous tumor cells. Although FDA granted Cabozantinib orphan drug status – a regulatory classification designed to streamline review of drugs for statistically uncommon conditions – its application is being tested against a number of types of cancer including melanoma, brain, breast, liver, prostate, kidney, ovarian, lung, and medullary thyroid cancer.
Recent coverage notes that side effects such as high blood pressure and hemorrhage are expected of cabozantinib. More worrisome safety issues may be on the horizon as the deaths of six patients taking cabozantinib were recently disclosed.
Wyeth Pharmaceuticals petitioned the United States Supreme Court to review a $58 million award granted to three plaintiffs who alleged that Prempro, a hormone replacement drug manufactured by Wyeth, caused their breast cancer. Wyeth alleged that the Nevada Supreme Court, which affirmed the verdict, had erred in not ordering a new trial after the trial court had reduced the jury’s original verdict of $134.6 million following the erroneous inclusion of punitive damages in the award.
As the healthcare industry becomes more digital, drug safety monitoring and prediction is the target of a recent innovation in medicine. IBM announced that doctors and researchers from Harvard Medical School and Brigham & Women’s Hospital would use an IBM Netezza system as a tool in drug safety.
The system will hold vast amounts of data concerning drugs and diseases. At this moment, the data come from insurance claim information of deidentified patients. Part of the system’s ongoing use includes regular updates of new claim information so that clinicians and researchers will have as up-to-date a picture of a drug’s safety profile and history as possible at the time of a query.
One application of the system is highlighting potential safety issues resulting from drug interaction. More sophisticated uses are also expected. The announcement predicts the system’s ability to analyze a drug in light of safety and efficacy profiles weighed against economic factors, known as health economics and outcomes research (HEOR).
A court precluded plaintiff’s expert from testifying that Premarin, a hormone replacement medication, increases the risk of breast cancer. Premarin, manufactured by Wyeth, is unique in the class of hormone replacement drugs in that it contains only estrogen, whereas most other hormone replacement drugs contain a combination of estrogen and progestin. The court excluded the causation evidence on the ground that the generally prevailing scientific view, as espoused by the National Cancer Institute, the American Cancer Society, and the National Institute of Health, is that Premarin does not cause breast cancer. The court also found that the studies plaintiff’s experts used to support their opinions focused exclusively on high-risk patients.