In this Issue

Dodd, Grassley Introduce Clinical Trials Bill

Judge Blocks March 7 Canadian Border Opening; Senate Okays Resolution Against USDA Rulemaking



Consumers Union Wants November, 2004 Suspect Animal Retested


Bush Nominates Agency Veteran Steve Johnson to Be EPA Administrator


USDA Deputy Secretary Jim Moseley Resigns


Court Tosses Bush Administration Farm Runoff Rule


HELP Hearings on Drug Safety Exhibit Voices of Reason

Senate Appropriations Structure Finalized

New Bills

Dodd, Grassley Introduce Clinical Trials Bill

On February 28, Senators Chris Dodd (D-CT), Chuck Grassley (R-IA), Tim Johnson (D-SD), and Ron Wyden (D-OR) introduced S. 470, the Fair Access to Clinical Trials Act. The bill intends to make publicly available more information about human clinical trials, including information about new trials as well as results from completed trials, for drugs, biological products, and medical devices. The legislation applies to all trials, whether privately or publicly funded.

The bill would amend the Public Health Service Act to expand requirements for registering clinical trials in the NIH-sponsored ClinicalTrials.gov, to include the registration of all trials (beyond Phase I safety studies), whether regarding serious and life-threatening illnesses or not. (Under current law and regulations, trials are listed if they are studying interventions for serious and life-threatening conditions.) The bill would require information about the purpose of the trial, primary and secondary endpoints, anticipated date of completion, recruitment information, etc. Registration in this data bank would be a condition of Institutional Review Board (IRB) approval of a clinical trial.

The bill also would require the establishment of a database of clinical trials results and that all sponsors of clinical trials supply information to this database. The provisions apply to all trials except Phase I studies that exclusively test safety or pilot studies that set design and operating specifications of a device. Submission of information to this database would be a condition of IRB approval of a trial. The required information would include a description of the product and the study; the purpose of the trial; an explanation of any difference between the estimated time of completion and actual completion of the trial; a summary of the results “in a standard, non-promotional format;” safety data, including a summary of adverse events; a discussion of how and who the results are being (or will be) reviewed, including whether FDA is currently reviewing an application or an explanation of why an application has not been submitted to FDA; information, within 90 days, of any FDA action, including any written consultation with the Office of Drug Safety; etc.

Failure to submit information to the trials results database would trigger a requirement that FDA publish the required information, to the extent the agency has it.

This legislation is virtually identical with bills introduced in the last Congress (H.R. 5252, Reps. Ed Markey (D-MA), Henry Waxman (D-CA), and others, and S. 2933, Senators Dodd, Ted Kennedy (D-MA), and others). No plans have been announced for consideration of S. 470 by the Senate Health, Education, Labor, and Pensions Committee, to which the bill is referred.

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Judge Blocks March 7 Canadian Border Opening; Senate Okays Resolution Against USDA Rulemaking

A Montana federal judge issued a preliminary injunction March 2 against USDA’s rulemaking to open the U.S. border to live cattle trade beginning March 7. Before the Department could decide if and when to appeal the injunction, the Senate okayed a “resolution of disapproval” of the prospective USDA border action.

The judge imposed the temporary ban from the bench to give himself time to study a complaint filed by Ranchers-Cattlemen Action Legal Fund (R-CALF) that the USDA rulemaking was premature and allowing Canadian cattle into the U.S. would expose both the U.S. beef herd and consumers to the risk of BSE. He also instructed attorneys from R-CALF and USDA to agree on schedule for a trial within 10 days so he could hear from experts to “clear up significant issues,” according to reports. USDA has not decided it if will appeal the injunction.

With the political cover provided by the injunction and in the face of a threatened presidential veto, the Senate moved quickly to approve 52-46 a resolution of disapproval of the USDA rulemaking to reopen the border. Just prior to the vote, the White House sent to the Hill a “Statement of Administration Position” (SAP) on the resolution, telling Senators the President was “strongly opposed” to the action. Now, the House must approve an identical resolution, but even if that were to happen – an acknowledged long shot – the President must sign the resolution. He has threatened to veto the legislation if it reaches his desk.

Rep. Stephanie Herseth (D-SD), who introduced the House version of the resolution of disapproval, is working to gain sufficient support to get her legislation to the floor. The National Farmers Union (NFU) said the resolution should be the House’s highest priority.

Secretary of Agriculture Mike Johanns said in separate prepared statements that he was disappointed in both the judge’s ruling and the Senate action. His frustration was amplified by House Agriculture Committee Chair Rep. Bob Goodlatte (R-VA), who with Rep. Robin Hayes (R-NC), chair of the panel’s livestock subcommittee, said, “We are disappointed the Senate acted so hastily in disapproving the USDA’s science-based minimal risk rule that would put us on the path to normalizing beef and cattle trade with Canada…The ramifications of the (Montana judge’s) ruling are devastating for the U.S. livestock and beef industry.”

Goodlatte’s committee held a hearing on the USDA rulemaking earlier this week, and he said that witnesses provided testimony as to how the status quo “is causing adverse economic harm to our processing industry, which has grave long-term implications for cattle producers. Further, the decision further undermines our nation’s credibility as we seek to eliminate non-tariff trade barriers around the world.”

In a related development, Rep. Jerry Moran (R-KS) introduced a resolution calling for sanctions against Japan if it doesn’t reopen beef trade with the U.S. Impatience with Japan led to President Bush and Secretary of State Condoleezza Rice raising beef trade issues in meetings with the Japanese. "It's no longer an agricultural issue...it's a political issue now," said USDA Undersecretary J.B. Penn. He told a House subcommittee USDA hopes Japan will remove its trade barriers soon. There is also a Senate version of the Japanese sanctions resolution. The Japanese government, which this week announced that nation’s 15th BSE case, has expressed its own disappointment in the congressional actions.

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Consumers Union Wants November, 2004 Suspect Animal Retested

The suspect BSE animal tested in November, 2004, and found to be negative for the disease under USDA testing protocols, should be retested using the Western blot test and samples sent to the United Kingdom for independent review, says Consumers Union. In a letter to Secretary of Agriculture Mike Johanns this week, Consumers Union said both of these testing options were used to confirm the Washington State BSE case in December, 2003.

Consumers Union said there are cases around the world where an animal showed positive results in a quick test, negative under immunohistochemistry (IHC) tests – the so-called “gold standard” of BSE testing -- and positive again under the Western blot test, when accompanied by a sodium phosphotungtinic acid (NaPTA) step in the process. Consumers Union told Johanns the IHC test is not as sensitive to detecting BSE as Western blot, and that European Union countries and Japan use the Western blot as the final word.

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Bush Nominates Agency Veteran Steve Johnson to Be EPA Administrator

Steve Johnson, a 24-year EPA veteran and acting EPA administrator since last January, was formally nominated to head the agency this week by President Bush. If confirmed, he will be the first professional scientist to head EPA. Johnson’s nomination was greeted with overall praise as he is generally regarded as a knowledgeable and even-handed regulator.

Prior to becoming acting administrator when former Utah Gov. Mike Leavitt left the post to become Secretary of HHS, Johnson was deputy EPA administrator, the agency’s number two spot. Prior to being named deputy, he was assistant administrator of EPA’s Office of Prevention, Pesticides & Toxic Substances (OPPTS). Johnson also served as deputy director of the Office of Pesticide Programs (OPP).

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USDA Deputy Secretary Jim Moseley Resigns

Jim Moseley, who served as deputy secretary of USDA for more than four years, resigned March 4. Moseley’s resignation was expected by most USDA observers.

USDA Secretary Mike Johanns said in a formal statement March 4 that Moseley “has served American agriculture well through an extensive and diverse career, and I wish him well in his future endeavors.”

Moseley, who prior to his USDA tenure headed a family pork operation in Indiana, also served as the first agriculture counselor and liaison between EPA and USDA during the Reagan administration. It was widely speculated Moseley might get the nod to become USDA secretary when former Secretary Ann Veneman resigned in January.

Johanns acknowledged Moseley’s contribution to both domestic and international programs, including fostering a “working relationship with the Afghan government and its people to help them rebuild the agricultural infrastructure of Afghanistan.” To complete “critical aspects of this important effort,” Johanns has asked Moseley to remain at USDA through June 1 as a special advisor focusing on the U.S./Afghan partnership.

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Court Tosses Bush Administration Farm Runoff Rule

A federal appeals court this week told the Bush White House its confined animal feeding operation (CAFO) rules to limit farm runoff violate the Clean Water Act (CWA) and must be revised, saying the rule fails to ensure so-called factory farms would be held accountable for animal waste runoff into waterways.

The ruling came in the 2nd U.S. Circuit Court of Appeals in New York on a suit brought by environmental groups who filed against the rulemaking in February, 2003. Nearly 30 years ago, Congress said CAFO’s were point sources for water pollution and needed to be regulated under EPA’s CWA permitting program. The Bush Administration’s 2003 rulemaking applied to 15,500 livestock operations across the country, and require not only permitting but for farmers to develop nutrient management plans to limit runoff or demonstrate they have no potential to discharge into waterways.

The court called the rules “arbitrary and capricious,” saying EPA could issue discharge permits without reviewing farm management plans, and that the rules didn’t ensure that each operation would comply with the effluent limitations and standards; the White House said the rules balance environmental protection with the needs of a competitive and economically important industry.

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HELP Hearings on Drug Safety Exhibit Voices of Reason

In two days of hearings March 1 and 3, the Senate HELP Committee took testimony from a variety of sources regarding the question of how effective FDA is in assuring the safety of prescription drugs. The hearing avoided hyperbole and over-reaction and focused on informed discourse with FDA officials, patient representatives, and others. Committee Chair Mike Enzi (R-WY) made the point early on that it is critical for the Committee to consider the facts carefully and evaluate all responsible issues and proposals before deciding whether significant changes, including legislation, are needed. Ranking Member Senator Ted Kennedy (D-MA) appeared to believe that some kind of legislation is needed. Specifically, he mentioned conflicts of interest on FDA advisory panels, the impact of Prescription Drug User Fee Act (PDUFA) speeding product approvals and drug safety efforts not keeping pace, and FDA needing authority to require label changes and post-market studies.

Testifying for FDA, Dr. Sandra Kweder, head of the Office of New Drugs, and Dr. Janet Woodcock, Acting FDA Deputy Commissioner for Operations, emphasized FDA is not disregarding drug safety and, in fact, 50% of the effort at the Center for Drug Evaluation & Research is devoted to drug safety activity. They also noted the recent initiatives intended to improve processes, including the establishment of a new drug safety oversight committee removed from the product review functions, a new process for resolving internal scientific differences, a substantial funding increase for the Office of Drug Safety in the 2006 President’s Budget, the newly announced Drug Watch web site, etc. In discussing whether additional authority is needed for FDA to require (rather than “negotiate”) label changes on marketed products, Woodcock noted earlier communication with the public regarding important safety information is better than waiting for label changes. This, she said, was a lesson learned from recent experience – when FDA has credible and valid risk information, that information should be communicated to patients and doctors even while the process of securing a label change may be under way. (Kweder stated, in response to a question, that additional authority to require label changes would be helpful to FDA; this response, a headline-maker, was tempered by Woodcock’s subsequent statements)

Woodcock further emphasized the importance of the link between the medical and scientific evaluation of a drug pre-market and the safety monitoring that continues throughout the product’s life. In response to a question as to whether the reviewer has a vested interest in defending the decision to approve a product and thus may be reluctant to have an unsafe product removed, she said while some may be concerned about “intellectual bias,” it is crucially important to involve a variety of people in safety discussions, including physicians who understand the condition and the need for the product. If we only looked at safety, she said, there would be no drugs on the market as no drugs are risk-free.

Some suggestions from witnesses for changes to improve drug safety activities included FDA engaging a public information campaign to ensure an understanding of drug risks and risk-benefit evaluation; providing additional legal authority and enforcement mechanisms for FDA to require label changes and post-market studies; restricting direct-to-consumer advertising (perhaps, for example, limiting advertising in the first few years a product is on the market); increasing FDA resources for drug safety, either by increasing the proportion of user fees allotted to drug safety activities or by increasing appropriations; establishing better and more independent mechanisms for post-market safety monitoring; improving adverse event reporting; authorizing FDA to address off-label prescribing; limiting availability of products approved on the basis of effect on surrogate endpoints; etc.

Among the witnesses, Abbey Meyers of the National Organization for Rare Disorders argued FDA’s success should be measured by its scientific excellence more than by its speed in approving new products. Nancy Davenport-Ennis of the National Patient Advocacy Foundation stated cancer patients in particular understand quite clearly that all drugs have risks and among the most important things is preserving both incentives for innovation and the ability of FDA to efficiently get drugs to patients. Dr. Thomas Fleming, University of Washington, stated that clinical trials must provide robust and compelling evidence of clinically-relevant benefit and reliable evidence that the benefits of a product outweigh its risks. One of Fleming’s concerns, expressed in prior activities as a member of numerous FDA advisory committees, remains the broad availability to patients, in a non-research setting, products whose benefits have been determined only based on the effects on surrogate endpoints and remain to be confirmed in post-market studies. In a striking comment on the current system, Fleming stated unconditionally that “FDA is not broken.”

Among other things, William Schultz, Zuckerman and Spaeder, reminded the committee a product recall does not indicate that a mistake was made in approving the product in the first place. He noted clinical trials not only cannot detect rare adverse effects, but also cannot detect a relationship between the experimental therapy and extremely common events (like heart attacks). Dr. Cecil Wilson, American Medical Association, noted the importance of improving the package insert, to make the information more understandable and the format more focused on putting up front information that is crucially important to patients and physicians. He did not support suggestions regarding restrictions on off-label prescribing or other limitations on physicians. Dr. Raymond Woosley, Critical Path Institute, University of Arizona, focused on what he termed a crisis in innovation. He said drug safety should be viewed in the broader context of what affects the future of the pharmaceutical industry and thus future patient access to new products. Changes that “fix” one part of the system without considering the others, he said, could be catastrophic.

Senators Orrin Hatch (R-UT), Richard Burr (R-NC), Johnny Isaakson (R-GA), Jack Reed (D-RI), and Patty Murray (D-WA) also participated in the hearing. Hatch noted the upcoming IOM study on FDA and drug safety and asked about mechanisms to improve adverse event reporting. Burr emphasized no drugs can be approved without clinical trial data, that it is incorrect to state that the COX drugs did not benefit patients, and that multiple label changes, including cardiovascular risk information, have been available on the COX products since the beginning. Murray asked whether additional authority is needed for FDA to require label changes or to withdraw a product from the market, the percentage of applications not approved, whether FDA works with manufacturers on the design of clinical trials to ensure that both safety and efficacy data are obtained, and what the relationship is between the FDA staff who review applications and those who do post-market monitoring.

New Bills

A number of new bills have been introduced. Click here to send a request for a copy of the text or more information about the bill.

S.470
Sen. Chris Dodd (D-CT) introduced a bill that would create electronic databanks for clinical trials of drugs, biological products, and medical devices.

S.471
A bill offered by Sen. Arlen Specter (R-PA) would provide for human embryonic stem cell research.

H.RES.137
Rep. Jerry Moran (R-KS) introduced a resolution with 52 co-sponsors regarding the resumption of beef exports to Japan. H.R.1118

H.R.1118
Rep. Collin Peterson (D-MN) proposed a bill to amend the Federal Crop Insurance Act to establish permanent authority for the Secretary of Agriculture to quickly provide disaster relief to agricultural producers who incur crop losses as a result of damaging weather or related condition in federally declared disaster areas.

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