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GAO: Agencies Earn Poor Grades in Rulemaking Transparency


By Mari Serebrov

Washington Editor


Even with grade inflation, the Department of Health and Human Services (HHS) and other federal agencies earned a "D" average for their efforts to request and respond to public comments when making major new rules. The grade dropped to an "F" for other rules.

Given the administration's response to the report card issued by the Government Accountability Office (GAO) last week, agency compliance with the public comment process that's required for most rulemaking isn't likely to improve any time soon.

To bring the grades up and improve the quality and transparency of the rulemaking process, the GAO advised the White House to issue guidance encouraging the agencies to respond to comments on final major rules. But the Office of Management and Budget (OMB) said that's not going to happen.

While it recognizes the value of public comment, OMB told the GAO that, unless required by law, the timing and extent of responses to public comment are up to the individual agencies, which have to set their own priorities and work with limited resources.

Agencies are required to publish a notice of proposed rulemaking (NPRM) for major rules – those that have an economic impact of $100 million or more per year – and then go through the process of requesting and responding to public comments. However, they can skip the NPRM process if they deem it would be "impracticable, unnecessary or contrary to the public interest," according to the GAO report.

The GAO found that agencies didn't publish an NPRM for about 35 percent of the 568 major rules and about 44 percent of the 30,000 nonmajor rules issued from 2003 through 2010. In most of those instances, agencies used the "good cause" excuse.

However, even when they didn't publish an NPRM, many agencies requested comment after a rule was issued. The problem is, that without an NPRM, rules are implemented before the public can comment and agencies are under no obligation to respond to the comments they receive.

Comments were requested on 77 of the 123 major rules issued without an NPRM in the GAO's sample. The agencies didn't issue a follow-up rule or respond to comments on 26 of the 77 rules, including ones with an annual economic impact of $1 billion or more.

One of those rules, issued by HHS, defined a pre-existing condition to implement part of the 2010 Affordable Care Act. HHS received 4,627 comments on the rule, but it didn't publish a response to any of them, according to the report.

"This is a missed opportunity," the GAO said, noting that when agencies respond to public comments, they often make changes that improve the rules.

"If agencies and the public are to fully benefit from the process of public comments, what matters is not simply providing an opportunity for comment but also public understanding of whether comments were considered," the GAO concluded.

FDA Adds PGx Guidance to Toolbox

Drugmakers have a new tool to help them evaluate early on how DNA and RNA variations in patients could affect the efficacy and safety of their drug candidates.

The tool, in the form of an FDA guidance, shows when and how genomic principles could be applied in early phase trials to address questions that might pop up during development and regulatory review.

"Genetic differences between individuals can affect virtually all aspects of a disease and its treatment, such as the rate of disease occurrence, the risk of disease progression or recurrence, the drug or drug class most likely to result in benefit, the therapeutic dose, the nature and extent of beneficial responses to treatment, and the likelihood of drug toxicity," the FDA said.

The most relevant genetic differences in drug development are those that occur with genes that predict disease development or that affect a drug's pharmacokinetics or its intended and unintended targets.

Recognizing that the use of pharmacogenomic (PGx) approaches during drug development varies by drug and is an evolutionary process that begins with discovery and continues through confirmation of clinical efficacy and safety outcomes, the FDA issued the new final guidance to hone in on the use of PGx data in the earliest stages of clinical development.

Thus, "Clinical Pharmacogenomics: Premarket Evaluation in Early-Phase Clinical Studies and Recommendations for Labeling" is specifically for use in exploratory and observational studies that are intended to generate genomic hypotheses that will be tested in later confirmatory trials.

For instance, early data on genomic-dependent dosing could be used to guide dose selection in later trials. And other genomic-based data from early trials could nail down the genetic and related biomarker data that should be collected in a larger number of patients in controlled trials, the FDA said.

Genomic data have become multi-use tools in drug development today, the agency noted, as they serve a variety of purposes in every phase of development, including:

identifying the basis for pharmacokinetic outliers and intersubject variability in clinical response;

ruling out the role of polymorphic pathways as clinically significant contributors to variable pharmacokinetics, pharmacodynamics, efficacy or safety;

estimating the magnitude of potential drug-drug interactions;

investigating the molecular or mechanistic basis for adverse reactions or a lack of efficacy;

designing trials to test for greater effects in specific subgroups.

A revision of a draft guidance released in 2011, the new final guidance describes when PGx studies are warranted and elaborates on topics such as targeted sample collection, sample retention, genotyping approaches, pooled analyses, dedicated prospective PGx studies, genetic substudies and safety PGx.

Avian Flu Research to Resume

The replay button is about to be pushed on avian flu research in the U.S.

The research, involving highly pathogenic avian influenza (HPAI) H5N1 viruses, was voluntarily placed on global pause a year ago because of concerns that it could inadvertently increase the transmission of the viruses to humans or other mammals.

But as soon as the HHS completes a framework for reviewing funding decisions regarding the research, scientists in the U.S. will resume their work. The framework is expected to be completed in the "next several weeks," according to National Institutes of Health Director Francis Collins.

In the past year, regulators worldwide have reviewed their policies and parameters for funding, conducting and communicating about the research.