Pharma Weakens FDA Oversight as the Price of Letting Congress Increase NIH Funding

by Daniel R. Hoffman, Ph.D.

Published Jul. 13, 2015, 3:03 p.m. ET

Last Friday, July 10, the United States House of Representatives passed H.R. 6 by a vote of 344-77. Pennsylvania Congressmen Barletta, Boyle, Brady, Cartwright, Costello, Dent, Doyle, Fattah, Kelly, Marino, Meehan, Murphy, Pitts, Rothfus, Shuster, and Thompson all supported its passage. The bill, known as the 21st Century Cures Act, is typical of legislation in the Obama era because it contains both progressive and plutocratic parts.

The progressive piece creates budget increases for the National Institutes of Health amounting to approximately 3% per year for three years, adjusted for inflation. The bill also provides another $2 billion per year for five years to create an "NIH Innovation Fund." These budget increases for NIH will help counteract the effects of sequestration and budget cuts that have hindered medical research funding during George W. Bush's administration and a Congress stalled by Republicans since 2010.

According to NPR health reporter Richard Harris, "The $30 billion budget for the National Institutes of Health has remained flat for that time, which means its buying power has actually dropped by 22 percent." Dave Moore of the American Association of Medical Colleges told Harris that twelve years ago, NIH funded approximately one out of every three grant applications it received. After a dozen years of Republicans and their disdain for government-supported medical research, the NIH is now able to fund only one out of every six grant requests.

More funding for NIH is all to the good, but other provisions of the bill could easily compromise the health of Americans that use prescription medications or devices.

Lobbyists for the pharmaceutical and device companies responsible for drafting the bill promoted it to Congress as a necessary step for speeding the approval of new products. But the record shows that approvals of new drugs and devices in the U.S. are already efficient and swift.

Dr. Jerry Avorn, a professor of medicine at Harvard Medical School, corroborated that fact in a June 25th article he published in the New England Journal of Medicine. Among other points, Dr. Avorn noted:

Once the FDA starts reviewing new drug applications, it approves them as quickly as any regulatory agency in the world (between six and ten months).
A third of new drugs are currently approved on the basis of a single trial that enrolled a median of only 760 patients.
More than two thirds of new drugs are approved on the basis of studies lasting six months or less, despite the fact that patients must take some of those medications for the rest of their lives.

But that brisk pace still is not fast enough for the pharma companies and other manufacturers of health care products. So they crafted the 21st Century Cures Act to push the FDA into using nontraditional methods for reviewing new drugs and devices that will rush through approvals even faster.

What are some of those nontraditional review methods favored by the 21st Century Cures Act? Dr. Avorn specified them.

1) The law encourages the FDA to approve devices that were tested in "shorter or smaller clinical trials" and drugs that weren't even tested in controlled clinical trials. Instead the agency is instructed to allow applications based on "experience," "observational studies" and "registries." Although data from those sources have their place, Dr. Avorn makes the point "that these approaches are not as rigorous or valid as randomized trials in assessing efficacy."

2) The Cures Act also encourages the FDA to rely more on surrogate measures rather than actual clinical end points to assess submitted drugs and devices. The difference is illustrated by the example of LDL cholesterol.

The clinical rationale for taking cholesterol medications is that by reducing the level of so-called bad cholesterol, LDL, they will help prevent heart attacks, strokes, and other cardiovascular episodes. But a clinical trial that follows two matched groups of patients – one of which receives the test drug, while the other receives a placebo – requires several years and commensurate expense. To save that money and time, the pharmaceutical industry and its paid researchers helped convince the FDA that LDL cholesterol is a valid surrogate marker. That means instead of waiting to see actual outcomes of who experienced more heart attacks and strokes and what those differences were, the sponsoring pharma just needs to compare LDL cholesterol levels in the two groups during a much shorter period. The agency currently uses surrogate markers in approximately half the new drug approvals it grants, but Avorn made the point that surrogates "may not always predict the drug's capacity to improve patient outcomes." Yet the Cures Act wants to get even more drugs approved on this basis.

3) The proposed legislation would make immediate changes with respect to new antibiotics and antifungals by enabling the FDA to approve them without clinical trials if the agency decides that these untested compounds can treat "serious or life-threatening infection[s]" in patients where no existing medications are available. "In place of proof," Dr. Avorn wrote, the legislation would empower the FDA "to accept nontraditional efficacy measures drawn from small studies" and other sources such as " 'preclinical, pharmacologic, or pathophysiologic evidence, nonclinical susceptibility, pharmacokinetic data, [and] data from phase 2 clinical trials.'"

The bill also creates a financial incentive for hospitals to administer costly but unproven antibiotics because that might encourage more widespread use of such drugs.

Other language gives the secretary of Health and Human Services the authority to "expand this nontraditional approval pathway to other drug categories as well."

4) The process of requiring informed consent from subjects in clinical trials has long been a pillar of ethical medical research. Now the 21st Century Cures Act creates an exception for studies where "the proposed clinical testing poses no more than minimal risk." As Dr. Avorn points out, "It is not clear who gets to determine whether a given trial of a new drug poses 'minimal risk.'"

So the 21st Century Cures Act seeks to get drugs approved without placebo-controlled trials, to use surrogate markers instead of actual outcomes studies, incentivize hospitals to use untested antibiotics and compromise patients' informed consent rights.

But that's not all. A section of the Affordable Care Act now requires drug and device makers to report all payments and gifts they make to physicians. The Cures Act would rescind that requirement, thereby making it more difficult to detect routine bribery.

Then there are the bribes that drug and device manufacturers already made to Congressmen to secure the bill's passage through the House. The Wall Street Journal reported data from the Center for Responsive Politics showing that members of the House Energy and Commerce Committee, which unanimously approved the bill and sent it to the full House, each received an average campaign contribution from drug and device companies of almost $70,000 during the last two years. The Committee's Republican chairman received a $302,700 contribution and the ranking Democrat got $174,072.

These donations mean that calling a Congressman to complain about the 21st Century Cures Act wouldn't prevent the bill from becoming law because Congress is already bought and paid for.

On the other hand, some calls to Congressmen might send the message that when it comes to health care, the public no longer consists of the contentedly corrupt meatheads that Washington assumes us to be. At some future time, that new awareness might deter a Congressman from reflexively grabbing all industry payoffs.