Research and Access Issues Challenge Policymakers

September 1, 2003
Jill Wechsler

Jill Wechsler is ACT's Washington Editor

Applied Clinical Trials

Applied Clinical Trials, Applied Clinical Trials-09-01-2003,

FDA plans to rewrite rules governing electronic records while offering new policies to encourage risk-based regulatory approaches to application review and inspections.

Prior to adjourning for its August recess, Congress took action to clarify the Food and Drug Administration’s authority to require sponsors to test drugs on children if the company fails to do so voluntarily. Policymakers have been successful in encouraging more pediatric studies by offering an additional six months of exclusivity on products where manufacturers underwrite such research. FDA backed up the voluntary incentive program with a 1998 rule mandating such studies. However, last year (17 October 2002), a federal court decided that FDA lacks authority to enforce such a policy. This prompted advocates to seek legislation clarifying the agency’s enforcement power in this area.

The Senate led the way, approving a bill (S. 650) that authorizes FDA to require pharmaceutical companies to test new drugs in children. Although manufacturers feel that FDA does not need specific authority to mandate pediatric testing, they decided not to fight the measure. Instead, industry succeeded in adding a “sunset” provision to the bill, which calls for Congress to reauthorize the test requirement policy in 2007 when the pediatric exclusivity program also expires. The House is expected to adopt a similar bill, possibly this month (September).

The Senate bill is the latest of several actions by Congress to expand government oversight of clinical research involving children. The new measure complements the Best Pharmaceuticals for Children Act, which Congress approved in January 2002 to reauthorize the pediatric exclusivity incentives program established in 1997. That legislation also called on the Institute of Medicine (IOM) to review federal regulations and to recommend best practices related to research involving children. Congress had adopted a children’s research measure in 2000 that prompted FDA to implement the federal “Subpart D” policy, adding uniformity to rules governing children in clinical investigations.

Advisors continue review

Those issues remain a top priority for the Health and Human Services Secretary’s new Advisory Committee on Human Research Protections (SACHRP), which held its inaugural meeting in July. The committee plans to pick up children’s research issues where its predecessor panel, the National Human Research Protections Advisory Committee, left off a year ago through a subcommittee on research in children. The subcommittee will further review how IRBs should define “minimal risk” related to pediatric research. It will also examine how IRBs should evaluate pediatric research that may not meet standard approval criteria but might be valuable in expanding researchers’ understanding of serious health problems affecting children. Other key issues to address include:

  • defining “assent” and “permission” for young study participants.
  • deciding whether consent requirements and other rules should vary with the age of a child.
  • defining “direct benefit” for children in studies.
  • exploring the idea of compensating study children and/or their parents.
  • recruiting children for clinical trials.

The panel may hold off launching an extensive review of pediatric research issues, though, until after the IOM completes its report on this topic next March (2004).

SACHRP also formed two other subcommittees. One will examine biomedical and behavioral research involving prisoners. The other will assess how well new accreditation programs are able to assess human research protection programs at academic research centers and other organizations that received federal research funding. The Bush administration has supported a voluntary, private-sector accreditation effort to improve compliance with standards among research institutions; and two organizations have launched accreditation programs. SACHRP plans to keep an eye on these efforts and to evaluate how well they improve research quality and oversight.

Access vs. efficacy

A perennial challenge for study sponsors and regulators is to accommodate demands from very ill patients for access to promising experimental therapies. Early access programs often make it more difficult to enroll participants in trials and usually rule out the use of placebo controls, which can complicate manufacturer efforts to gain clear evidence of efficacy. Now the Washington Legal Foundation (WLF) is acknowledging the need to address clinical research concerns, while seeking to liberalize FDA policies that limit early access to potentially life-saving drugs. The conservative legal group and the Abigail Alliance for Better Access to Developmental Drugs filed a suit 28 July 2003 charging that FDA limits on patient access to investigational new drugs violate individuals’ constitutional rights. The plaintiffs want FDA to revise its new drug approval process to add a “tier 1” approval program, as outlined in WLF’s June citizens’ petition to the agency. The new system would allow sponsors to sell promising investigational drugs, but only to seriously ill patients who lack alternative treatment. Sponsors would be able to charge more than a minimal recovery rate, providing resources for manufacturers to expand production of critical test therapies that show early signs of efficacy.

In its June petition, WLF calls for FDA to grant tier 1 initial approval to products that demonstrate safety in Phase 1 studies plus show evidence of efficacy in limited patient case histories. Tier 2 approval would be similar to FDA’s current accelerated approval program, and tier 3 would be comparable to full approval. However, WLF would limit tier 1 access to patients found ineligible for or denied participation in a clinical trial. And sponsors seeking tier 1 approval would have to continue “diligent pursuit” of clinical trials and other testing required for accelerated or full approval.

FDA has until early October to seek dismissal of the suit. The agency doesn’t want to be required to approve investigational treatments, although it has been willing to encourage compassionate use programs involving new therapies for very ill patients. But even without the lawsuit, the WLF petition raises important issues governing access to life-saving investigational products. The proposal puts pressure on FDA to address whether manufacturers should be able to charge more for test therapies and how agency policies could be revised to expand compassionate use and accelerated access programs.

Cutting back pharma prices

Patient advocates and some legislators seek to increase consumer access to all medicines by reducing FDA restrictions on drug reimporting. In July, they succeeded in gaining House approval of a controversial bill that makes it easier for individuals, pharmacists, and wholesalers to reimport lower-cost drugs from abroad. Even though the measure may be impractical and undermine drug safety assurances, a significant group of Republicans joined with most Democrats to adopt the policy. An underlying aim was to voice opposition to industry pricing strategies that rely on high U.S. revenues to support worldwide research and development.

FDA and manufacturers contend that boosting the already soaring volume of pharmaceutical imports will only open the floodgates to more counterfeit medical products. Industry critics, however, claim that drug counterfeiting is on the rise because legitimate pharmaceuticals are too expensive in the United States. The issue is on the table for House and Senate leaders trying to negotiate an acceptable Medicare pharmacy benefit program. There is strong bipartisan opposition in the Senate to any reimport program that FDA cannot certify for safety. A more limited reimport program may prevail in the end, but even House leaders who opposed the bill acknowledge that if Medicare is to pay billions for outpatient prescription drugs, industry has to offer U.S. patients fairer prices.