Jonathan J. Darrow

Institutional Corruption of Pharmaceuticals and the Myth of Safe and Effective Drugs

Over the past 35 years, patients have suffered from a largely hidden epidemic of side effects from drugs that usually have few offsetting benefits. The pharmaceutical industry has corrupted the practice of medicine through its influence over what drugs are developed, how they are tested, and how medical knowledge is created. Since 1906, heavy commercial influence has compromised congressional legislation to protect the public from unsafe drugs. The authorization of user fees in 1992 has turned drug companies into the FDAs prime clients, deepening the regulatory and cultural capture of the agency. Industry has demanded shorter average review times and, with less time to thoroughly review evidence, increased hospitalizations and deaths have resulted. Meeting the needs of the drug companies has taken priority over meeting the needs of patients. Unless this corruption of regulatory intent is reversed, the situation will continue to deteriorate. We offer practical suggestions including: separating the funding of clinical trials from their conduct, analysis, and publication; independent FDA leadership; full public funding for all FDA activities; measures to discourage R&D on drugs with few, if any, new clinical benefits; and the creation of a National Drug Safety Board.

Trends in utilization of FDA expedited drug development and approval programs, 1987-2014: cohort study

Objective To evaluate the use of special expedited development and review pathways at the US Food and Drug Administration over the past two decades. Design Cohort study. Setting FDA approved novel therapeutics between 1987 and 2014. Population Publicly available sources provided each drug’s year of approval, their innovativeness (first in class versus not first in class), World Health Organization Anatomic Therapeutic Classification, and which (if any) of the FDA’s four primary expedited development and review programs or designations were associated with each drug: orphan drug, fast track, accelerated approval, and priority review. Main outcome measures Logistic regression models evaluated trends in the proportion of drugs associated with each of the four expedited development and review programs. To evaluate the number of programs associated with each approved drug over time, Poisson models were employed, with the number of programs as the dependent variable and a linear term for year of approval. The difference in trends was compared between drugs that were first in class and those that were not. Results The FDA approved 774 drugs during the study period, with one third representing first in class agents. Priority review (43%) was the most prevalent of the four programs, with accelerated approval (9%) the least common. There was a significant increase of 2.6% per year in the number of expedited review and approval programs granted to each newly approved agent (incidence rate ratio 1.026, 95% confidence interval 1.017 to 1.035, P<0.001), and a 2.4% increase in the proportion of drugs associated with at least one such program (odds ratio 1.024, 95% confidence interval 1.006 to 1.043, P=0.009). Driving this trend was an increase in the proportion of approved, non-first in class drugs associated with at least one program for drugs (P=0.03 for interaction). Conclusions In the past two decades, drugs newly approved by the FDA have been associated with an increasing number of expedited development or review programs. Though expedited programs should be strictly limited to drugs providing noticeable clinical advances, this trend is being driven by drugs that are not first in class and thus potentially less innovative.

Practical, Legal, and Ethical Issues in Expanded Access to Investigational Drugs

The authors review the FDA policies and procedures that permit some patients with serious conditions to receive investigational drugs before formal product approval and examine the legal and ethical issues associated with expanded access.

New FDA Breakthrough-Drug Category — Implications for Patients

In July 2012, the FDA Safety and Innovation Act created the “breakthrough therapy” designation to expedite development of therapies for serious diseases when evidence suggests substantial superiority over existing options. The authors discuss implications of the new designation.

Drug Development and FDA Approval, 1938–2013

This interactive graphic shows major legislative and regulatory events related to approval of new drugs by the Food and Drug Administration (FDA), drug approvals by year and by therapeutic category, and trends in the use of the FDAs various programs for expedited approval.

FDA Designations for Therapeutics and Their Impact on Drug Development and Regulatory Review Outcomes

New prescription drugs receive approval from the US Food and Drug Administration (FDA) based on tests establishing safety and adequate and well‐controlled trials demonstrating “substantial evidence” of efficacy. However, a number of legislative and regulatory initiatives, the most recent being the breakthrough therapy designation created in 2012, give the FDA flexibility to approve drugs on the basis of less rigorous data in situations of greater clinical need. These expedited development and review pathways now contribute to a majority of all new drug approvals and have important benefits in encouraging efficient availability of transformative drugs. They also have a number of risks, including a heightened possibility that the drugs will be discovered to be ineffective or unsafe after widespread use, and confusion by patients and physicians over what it means for a product to be “FDA approved.”

The FDA’s Expedited Programs and Clinical Development Times for Novel Therapeutics, 2012-2016

The FDA’s Expedited Programs and Clinical Development Times for Novel Therapeutics, 2012-2016 The US Food and Drug Administration (FDA) has 4 expedited programs to speed the development and review of drugs treating serious diseases: (1) priority review leads to FDA review in 6 months (vs 10 months for standard review); (2) accelerated approval permits approval based on surrogate measures; and (3) fast-track and (4) breakthrough therapy programs are intended to reduce the duration of clinical trials (Table).1 Clinical development times for drugs in these expedited programs, particularly the newly created breakthrough program (enacted in 2012), have not been comprehensively assessed. We analyzed clinical development times within each of the 4 expedited programs separately and between drugs qualifying for any vs no expedited program. Because fast-track and breakthrough programs are intended to abbreviate the overall drug development process, we also examined development times for drugs receiving either or both of these 2 programs (regardless of other programs).

Recent developments in health law. Essential medicines: why international price discrimination may increasingly be the wrong solution to a global drug problem.

The theoretical appeal of international pharmaceutical price discrimination derives from its ability to place essential medicines within reach of patients in low-income countries, while simultaneously allowing industry to recoup its significant research and development costs by selling the same drugs at much higher prices in high-income countries. Unfortunately, there are a number of challenges to the international price discrimination of drugs that makes this approach unlikely to lead to desired results. These include the arbitrage challenges (Internet sales, pharmaceutical tourism, reference pricing, and an absence of patent protection), fairness and political challenges, and effectiveness limitations (even low prices are not low enough to enable access for a majority of poor people). This article explores these challenges, and concludes by contrasting the recent success of advance market commitments (AMCs).

Will inter partes review speed US generic drug entry

A new extra-judicial pathway for challenging pharmaceutical patents has intensified patent challenges and helped to clear the way for earlier generic entry.

Speed, Safety, and Industry Funding — From PDUFA I to PDUFA VI

The FDA Reauthorization Act of 2017 includes the sixth version of the Prescription Drug User Fee Act. User fees have accelerated drug approvals in the context of inadequate funding of the FDA, and industry now pays 75% of the costs of the scientific review of drugs.