The HHS report noted that 80% of approved marketing applications for drugs and biologics contained data from foreign clinical trials. More than half of clinical-trial subjects and sites were located outside the United States. Western Europe accounted for most foreign clinical-trial subjects and sites. Central and South America had the highest average number of subjects per site. Overall, FDA inspected clinical investigators at only 1.2% of all clinical-trial sites for applications approved in fiscal year 2008. It inspected 1.9% of domestic clinical-trial sites and 0.7% of foreign clinical-trial sites. The report said that challenges to conducting foreign inspections and data limitations inhibit FDA’s ability to monitor clinical trials, which included problems of having early-phase clinical trials being conducted outside the US without investigational new drug (IND) applications.

In its report, HHS recommends that FDA require standardized electronic clinical-trial data, monitor trends in foreign clinical trials not conducted by INDs, and to continue to explore ways to expand its oversight of foreign clinical trials. Such recommendations are reasonable, but they also raise larger policy questions that come into play with the increased globalization of the pharmaceutical industry. That is, given the nature of the products being made and the attendant regulation that is required, should a different model of business practices and regulation apply to pharmaceutical products compared with consumer and industrial products? Should another set of rules of apply?

There is no easy answer to that question as it requires a balance of free-market principles with public regulation. Drug products, unlike consumer and industrial products, require a higher level of regulatory oversight to ensure their safety and quality. Products developed or manufactured outside the US are neither implicitly better or worse than products developed or manufactured in the US. But given the limitations of financial resources and jurisdictional authority of US federal agencies outside the US, is it a prudent course to have clinical development or manufacturing of pharmaceutical products that are targeted for the US market, to be performed outside the US? Is this question an economic debate of free trade versus protectionism or a broader policy matter in ascertaining the relevance of domestic regulation in a global marketplace? Should regulation dictate business practice or business practice dictate regulation?

It seems now that we have a hybrid response. During the past several years, FDA has responded with the opening of offices in China, India, Central America, and South America as a way to increase its oversight of pharmaceutical development and manufacturing outside the US, which is a good move in the interest of public safety. But again, it raises another broader philosophical question: should federal resources be used to indirectly support offshoring functions outside the US? There is an ongoing policy debate as to how to increase the US position in science, technology, engineering, and mathematics (STEM) with initiatives supporting STEM activities in education and suggestions to foster competitiveness in innovation. But in the case of pharmaceutical products, is there a disconnect in federal policy, where on one hand we want to encourage STEM activities domestically, but on another hand are indirectly fostering STEM activities outside the US?

A lot to consider. Admittedly, it is a difficult balance of short-term, long-term, economic, and scientific goals, but perhaps one in which the sum of the parts rather than the individual parts should be considered.

Deputy FDA Director Joshua Sharfstein acknowledged in a press briefing that some proprietary information—the formula for making a certain pill, for example—may remain confidential. He also conceded that concerns about patient privacy and other issues may limit full data transparency. But this initiative clearly opens the door to broader disclosure of records that manufacturers regard as private property. Unpublished clinical and preclinical studies, product formulations, and manufacturing data have long been considered trade secrets, and pharmaceutical companies are likely to mount a stiff defense of the rules and laws that protect their rights.

FDA may have more leeway to expand transparency about its own decisions and regulatory actions. The agency currently announces product approvals, but not when it turns down an application. And it’s up to manufacturers to disclose when they file an application or withdraw a submission. Margaret Hamburg, FDA commissioner, told reporters that she wants to address complaints that FDA is a “block box” by clarifying agency processes. Agency decisions often have good explanations, and Hamburg would like to see what information could be made available to avoid confusion and criticism.

FDA will begin its transparency review with a public meeting, and Hamburg expects a report by year’s end that will describe what additional information the agency can release on its own and what changes require new regulations or Congressional action. The pendulum clearly is swinging towards the transparency side, and everyone is watching to see whether it swings too far.

Pharmaceutical Technology has added FDA’s transparency blog to its own blogroll.

The US Food and Drug Administration is focusing its efforts on Institutional Review Boards (IRBs), which approve and monitor clinical trials. The agency recently told a hearing of the House Subcommittee on Oversight and Investigations that it will require IRBs to register with them, beginning in July 2009. The registration process will be the basis for a database of IRBs, and this tool will help FDA monitor and inspect these bodies. The agency also said it would establish voluntary guidelines for drugmakers and IRBs.

FDA was stirred to action when the Government Accountability Office (GAO) reported that it had successfully set up a phony IRB, registered it with the US Department of Health and Human Services, and gotten approval to test an imaginary medical device on human subjects. The GAO also obtained a real IRB’s approval for a fake protocol for human-subjects research, although the protocol contained demonstrably false claims that the device to be tested had FDA approval.

Last week the Association for the Accreditation of Human Research Protection Programs gave Pfizer its accreditation for protecting the rights of its human clinical trial subjects, and the company pledges to carry out trials according to the International Conference on Harmonization’s international standards of good clinical practice. Despite Pfizer’s good will, I think FDA needs binding, not voluntary, rules to ensure that all pharmaceutical companies protect their trial patients’ safety. Human life is precious and demands no less.

The trial results will likely have an impact on the company’s financial picture. Genentech last Thursday released its fourth-quarter and year-end results for 2008, reporting a 47% rise in fourth-quarter earnings. Arthur D. Levinson, PhD, Genentech’s chairman and CEO, said the company was happy with “another year of solid financial growth.” Levinson also said that the company has the potential to receive four FDA approvals and plans to file more than 10 regulatory applications in 2009.

But some are disappointed in the company’s earnings outlook and are concerned about its slowing sales growth. According to an AP report, Avastin sales are rising but the growth is slower than expected.

Investors continue to wait for news about Roche’s takeover attempts of the company. In July, Genentech rejected Roche’s $43.7 billion offer, or $89 per share, as too low. Analysts predicted last fall that Roche could up the bid to as much as $100 per share, but these days the estimate falls near the $95 mark. Bloomberg reports that last Monday, Roche CFO Erich Hunziker said in a speech at the J.P. Morgan Healthcare Conference in San Francisco that the deal to acquire Genentech was “on track.” He wouldn’t comment on the possibility of a raised bid, but he reportedly said, “Let the independent directors of Genentech do their job. Everything is going as planned.”

These technologies can help create a greater understanding of disease and of potential drug effects, according to a June 20 PWC release. Virtual R&D can also help take a big chunk out of rising clinical-trial costs.

“Models of the heart, organ, cells systems, and musculoskeletal architecture are already being developed by academics around the world. Such technologies can be used to simulate the physiological effects of interacting with specific drugs and identify which drugs have a bearing on the course of a disease,” said Steve Arlington, PWC global pharmaceutical and life sciences industry advisory leader, in the release. “Some companies using virtual technology have reduced clinical-trial times by 40% and reduced the number of patients required by two-thirds.”

PWC points out that virtually-modeled molecules will still have to be tested in real human beings, but that the number of live individuals typically tested in a trial can be greatly decreased.

But is virtual research something industry is ready for? I can just imagine FDA trying to put together a “virtual” inspection guideline. More important, will real, live patients trust a drug’s efficacy and safety based on research done using not-so-real patients?

Read PWC’s Pharma 2020: Virtual R&D report.

Beyond the fact that disqualifications seems to be on the rise, there is the issue of case delays. The ever-overburdened FDA has as many as 12 open suits—some of which have been open for a decade—against researchers who allegedly violated rules to protect patients and ensure accurate data, according to Bloomberg News.

The problem with unresolved cases is that researchers still have access to investigational new drugs and trial patients.

“There’s just no excuse for not invoking the authority FDA already has to rapidly disqualify liars from taking any further role in these drug studies,” says US Rep. Joe Barton (R-TX) in House Energy and Commerce Committee website article. He and a few other Congressmen have been trying to get the GAO to take action on this matter. Read his March letter to GAO.

FDA has the right to disqualify or “totally restrict” a clinical study investigator from conducting further research if they repeatedly or deliberately fail to comply with current requirements, or if the researcher repeatedly or deliberately submits false information to the trial sponsor or to FDA itself. Once disqualified, the researcher can no longer receive investigational drugs, biologics, or devices. The agency can also apply a lesser “restricted” classification to individuals; these investigators are still able to work with investigational products but have some limitations that they agree upon with FDA. But until these classifications are made, researchers are free to carry out their work.

The latest person to receive the so-called Scarlet letter, is Maria Anne Kirkman Campbell, who pleaded guilty to fraud in 2003 after working on a Sanofi-Aventis SA antibiotic study. Even though her case took place five years ago, Campbell just received her disqualification status last month.

Check out FDA’s disqualified list and let us know your thoughts on this issue.

 As a parent, I completely understand. The well-known cases of recalls, contaminations, long-term side effects, and adverse events has lead to great public mistrust. Coincidentally (or perhaps as a result), the Pharmaceutical Reseach and Manufacturers of America (PhRMA) last week started a new ”Sharing Miracles” television campaign to help educate the public about what drug companies are working on and the good the industry has done so far. The first wave will discuss achievements in cancer research, which according to PhRMA, is the number one area of medical research.

Will this be enough to encourage more parents to get involved in pediatric clinical trials? Will they know that clinical trials during the past 30 years have improved survival rates for children from less than 50% to more than 85% (according to V. Castle, MD, chair of the Department of Pediatrics at the U of Michigan Health System)? What role does the pharmaceutical industry play in ensuring patients are well educated about participating in these trials to ensure innovation progresses?

Exhibit A: InterMune CEO W. Scott Harkonen paid $37 million to settle felony charges of violating the Federal, Food, Drug, and Cosmetic Ac for falsely promoting Actimmune (interferon gamma-1b) for unapproved uses as a treatment for idiopathic pulmonary fibrosis. The California-based company released selective data from its clinical research.

Exhibit B: Houston neurologist Arthur Ericsson may be disqualified by FDA (let’s hope he is) for giving an investigational new drug for autoimmune/inflammatory conditions involving the nervous system to at least six patients without an approved IND application. He had 22 patients sign informed consent documents that were not legally accurate. Even scarier, Ericsson reportedly received a warning letter 15 years ago, in 1993, for violating a clinical hold on another investigational drug in which he failed to maintain adequate records of the drug or of the patients’ case histories. How is this guy still allowed into any labs?

Exhibit C: According to a recent study published in Acta Paediatrica by researchers at the University of Nottingham, out of 739 studied pediatric clinical trials, only 2% reported using independent safety monitoring committees. These committees can help lead to the early detection of adverse drug reactions. Compare the 2% statistic to the fact that 71% of the trials reviewed reported adverse events.

There are several other examples of clinical trials and research being conducted inappropriately. With this information in hand, I know I wouldn’t consider signing up for a clinical trial. How can industry expect others to? What proof do patients have that a trial, a researcher, a drug, is safe—or for that matter, legal?