Marcia M. Boumil

Conflict of interest in open-access publishing.

Open-access journals, in which the authors pay a publication fee, have an incentive to publish a high volume of articles. This letter explores the matter of conflict of interest in the growing number of these journals.

Off-Label Marketing and the First Amendment

On December 3, 2012, a three-judge appeals-court panel took a controversial leap by ruling that the government cannot prosecute pharmaceutical manufacturers and their representatives “for speech promoting the lawful, off-label use of an FDA-approved drug.”

Whistleblowing in the pharmaceutical industry in the United States, England, Canada, and Australia.

Fraud and abuse in the spending of public monies plague governments around the world. In the United States the False Claims Act encourages whistleblowing by private individuals to expose evidence of fraud. They are rewarded for their efforts with monetary compensation and protection from retaliation. Such is not the case in Canada, England, and Australia. Although some recent legislation has increased the protections afforded to whistleblowers, they are still likely to be viewed more as disloyal employees than courageous public servants, and there is little incentive to risk their jobs and reputation. Qui tam laws provide a police force of thousands in the effort to reduce rampant fraud, waste, and abuse, and would be an asset in any health-care system where pubic health policy requires conservation of resources.

On Access and Accountability — Two Supreme Court Rulings on Generic Drugs

In June, the U.S. Supreme Court issued two rulings regarding the marketing of generic drugs. The decisions have mixed implications for consumers, but given the size and growth rate of the industry, their impact can be expected to be substantial.

Transparency in research and its effect on the perception of research integrity.

Pharmaceutical companies routinely engage faculty from academic medical centers to participate in biomedical research. Faculty contribute expertise and research subjects and often receive considerable compensation for their efforts. Because the role of the researcher can be compromised by financial conflicts of interest, disclosure of such relationships is routinely required. The effect of such disclosure is not entirely clear, however, and studies have yielded inconsistent results on how those receiving financial disclosures perceive the integrity of the research. Reviewing the literature, we conclude there is little consensus on how the disclosure of a financial relationship with an industry sponsor affects confidence in the research. We also conclude that is it unclear whether the new Patient Protection and Affordable Care Act will substantially alter the landscape.

Theranos Experience Exposes Weaknesses in FDA Regulatory Discretion

Beginning in late 2015, the Wall Street Journal published a series of articles on the American biotech startup company, Theranos.1–13 Founded in 2003, Theranos promised fingerstick and small volume blood-testing technology that would revolutionize the way small blood samples could be tested for a myriad of diagnostic applications. At its pinnacle 10 years later, Theranos was valued at

Legal Liability of Generic vs Brand Drug Manufacturers for Inadequate Product Labels

9 billion. Theranos succeeded in exploiting the Food and Drug Administration (FDA)’s regulatory enforcement discretion, which allowed it to delay FDA review of its technology; it gained Centers for Medicare & Medicaid Services (CMS) certification for its laboratories; and it secured retail shelf space at Walgreens. All of this would eventually be undone: (1) Theranos was cited by FDA inspectors for misclassifying its nanotainer blood-collecting technology and for deficiencies in documentation of manufacturing compliance; (2) it was sanctioned by CMS, including revocation of its certification; and (3) it was forced to close down its laboratory and retail operations to concentrate on a single miniature testing machine. What did Theranos hope to accomplish, and how did the FDA’s regulatory enforcement discretion help to make it happen? The goal that had been articulated by senior Theranos management to a wide audience was that Theranos would be the first to commercialize a laboratory testing platform that could accurately test a small volume of blood on site: in a drugstore, a doctor’s office, or another convenient location.14 Hospital managers and investors were intrigued by claims that 30 tests could be rapidly run on a single droplet of blood.15 Consumers would have direct access to technological breakthroughs that make it “possible to quickly process the full range of laboratory tests from a few drops of blood.”3 In a race to be first in a highly competitive market, Theranos attracted high-profile, albeit primarily nonscientific, investors to sit on its board, and it exploited regulatory ambiguities to find its way into this

Medical Schools’ Competition for Clinical Training Sites

75 billion-a-year commercial market.1 Eschewing a traditional, thorough, project management-driven, science-focused development program, Theranos appeared to presume that its technology would eventually be able to do what it promised and develop the necessary test results to prove its capability. Regrettably, that is not how the story unfolded.

Commentary: Collaboration in dual degree programs contributes something new to both fields

Massachusetts is the latest of state highest courts to address the issue of “innovator liability”: brand-name pharmaceutical manufacturers who are exposed to legal liability for generic forms of their brand products that cause injuries to consumers. In Rafferty v Merck & Co Inc (2018),1 the Massachusetts Supreme Judicial Court addressed a claim against Merck based on failure to warn of an adverse drug effect brought by a patient, Brian Rafferty, who took finasteride, a generic version of Merck’s brand-name drug Proscar. Generic finasteride was prescribed to the plaintiff to treat an enlarged prostate. Almost immediately after starting the drug, Rafferty experienced symptoms of erectile dysfunction and decrease in libido, and despite weaning of finasteride, the symptoms persisted. The product label for finasteride warned of the potential adverse effect of sexual dysfunction but also reported that it would resolve if the drug were discontinued. Rafferty alleged that Merck had information in its possession that the adverse effect could persist even if the drug were discontinued and had even changed the label for Proscar in several non-US markets but failed to do so in the United States. The legal question in the case is: Should brand companies be held liable for harm resulting from a generic counterpart that they did not produce? Generic manufacturers are required by law to maintain a label identical to the brand’s label when marketing their drug.2 A key feature of the federal law governing drug product labeling is that brand manufacturers must ensure that the label is adequate, accurate, and up to date, and generic manufacturers are obligated to use an identical label. The brand manufacturer is also obligated to monitor drug safety after receiving US Food and Drug Administration (FDA) approval to market the drug and to modify the label warnings when necessary as new safety data become available. Why not sue the generic manufacturer? In PLIVA Inc v Mensing (2011),3 the US Supreme Court held that a consumer of a generic bioequivalent of a brand-name product may not bring a claim against a generic drug manufacturer stemming from failure to warn of an adverse drug effect because the FDA controls the warning label and generic manufacturers have no authority to modify the label. Thus, legal action against the generic company was preempted. Furthermore, the US Supreme Court in Mutual Pharmaceutical Co v Bartlett (2013)4 held that state law claims against a generic manufacturer alleging design defects based on inadequacy of the warning in the label are also preempted by the FDA regulations. In both cases, the patients harmed by adverse effects of generic drugs had no legal recourse based on the drug label’s failure to warn of these adverse effects.5 At this point, only Congress could change this situation by writing new law. Whether generic manufacturers should be expected to investigate the accuracy of the labels for the drugs they are marketing does not currently appear to be required by law. For example, in the case of Rafferty v Merck & Co, the generic manufacturer could have discovered that Merck had changed the label in a number of non-US markets. In light of the FDA regulatory environment, a number of state courts have addressed the issue of whether a consumer injured by a generic drug should be able to bring legal action against a brand manufacturer that negligently, recklessly, or intentionally fails to warn of known adverse drug effects that cause injury. Massachusetts is the latest court to join a minority of courts holding that a brand-name manufacturer failing to update its warning label with relevant safety information may be held liable. The standard in Massachusetts is not one of mere negligence but requires recklessness or intentionality. The court justified its decision on the basis of public policy concerns for the safety of consumers while also considering the legal burden on brand-name manufacturers. In December 2017, California became the first state to embrace the doctrine of innovator liability when the Supreme Court in T.H., a Minor, etc, et al, Plaintiffs, and Appellants v Novartis Pharmaceuticals Corp6 held that a brand-name manufacturer incurs a duty to warn consumers that extends to its generic counterparts, even though the brand manufacturer did not produce the generic product. In this case, it was alleged that a mother’s ingestion of the generic drug terbutaline to prevent preterm labor resulted in her twins developing autism. Holding that the brandname manufacturer as innovator of the drug has a duty to warn consumers of the generic counterpart, the California court held that it was foreseeable that such consumers would rely on its label and the brand manufacturer was in the best position to warn of harmful effects and modify an outdated label. In reaching its conclusion, the court relied on the rationale of a previous California case, Conte v Wyeth.7 Garner v Johnson & Johnson et al8 is another state decision from the Central District of Illinois allowing innovator liability for failure to warn of injury by a consumer of Johnson & Johnson’s generic antibiotic counterpart, fluoroquinolone. In Garner v Johnson & Johnson et al, the plaintiff sued both the brand and generic manufacturers. The claim against the generic manufacturer was dismissed on the basis of FDA preemption under PLIVA Inc v Mensing, but the court denied a motion to dismiss as to Johnson & Johnson, holding that the brand has the “unilateral ability to strengthen the label,” and VIEWPOINT

In ... and out: open access publishing in scientific journals.

Medical Schools’ Competition for Clinical Training Sites To the Editor: Why would a prominent medical school in New York send its thirdand fourth-year students to Texas for clinical training, while an offshore medical school sends its students to the New York hospital that once trained the New York school’s students? Medical schools have increased class size dramatically over the past decade, and more than two dozen new medical schools have been accredited. The numbers of physician assistant, nurse practitioner, osteopathic, and other educational programs have grown even more. Today there are upwards of 33% more students requiring clinical training than there were 10 years ago. Since enrollment is constrained primarily by the number of clinical teaching slots available, it is not surprising that high-quality training sites are coveted, and schools find themselves competing for clinical space by acquiring sites from one another. While medical schools that own hospitals have greater control over clinical training capacity, those that do not may find themselves competing vigorously for clinical teaching venues, and sometimes having to “outbid” other medical schools. The moment has come for a national dialogue about how to realign medical schools with local clinical teaching sites so that schools throughout the country can train their students in reasonable proximity to their schools.