CDER’s Woodcock Details Expanded Authority at Post-Approval Summit

By Sara Gambrill

Opening the Post-Approval Summit at Harvard on May 14 and 15, keynote speaker Janet Woodcock, M.D., director of the Center for Drug Evaluation and Research (CDER), Food and Drug Administration (FDA), outlined her agency’s expanded authorities in the area of post-approval research oversight brought about by the passage of the FDA Amendments Act (FDAAA) into law at the end of March.

“FDAAA stipulates many new tasks and authorities for CDER,” said Woodcock.

Another common theme discussed by presenters who spoke later in the day at the conference was that, with the passage of FDAAA into law, the bifurcation of pre-approval and post-approval drug oversight would be eliminated. Woodcock described FDAAA as a “profound change” that would lead to “equal focus and accountability [being] placed on overseeing the safety of marketed drugs as on the evaluation of new drugs.”

Among its new authorities, CDER will be able to require a Risk Evaluation and Mitigation Strategy (REMS), which is a strategy to manage a known or potential serious risk associated with a drug or biological product. A REMS will be required if FDA finds that a REMS is necessary to ensure that the benefits of the drug or biological product outweigh the risks of the product, and FDA notifies the sponsor. A REMS can include a Medication Guide, Patient Package Insert, a communication plan, elements to assure safe use, and an implementation system, and must include a timetable for assessment of the REMS. Some drug and biological products that previously were approved/licensed with risk minimization action plans (RiskMAPs) will now be deemed to have REMS.

At the end of Woodcock’s talk and others’, audience members from pharma and CROs asked what the difference between a REMS and a RiskMAP was and whether the REMS would replace the RiskMAP. These questioners were invariably referred to the agency’s lawyers. REMS relationship to RiskMAPs was not made clear at the conference.

A common theme throughout the presentations was the need for new technology to help the agency offer better pharmacovigilance.

CDER’s implementation strategy is called Safety First/Safe Use. It is the initiative under which the agency’s goals will be accomplished.

Woodcock discussed plans for the agency’s pharmacovigilance and active surveillance, acknowledging that it had to build new ways to do post-marketing surveillance instead of the Medwatch program, which involves voluntary reporting of spontaneous adverse events from marketed drugs by physicians. The goals for the agency’s new system are to include 25 million patients by July 1, 2010 and 100 million patients by July 1, 2012. “It’s no problem to set up the system, analyzing data is the problem,” said Woodcock. But she did also express budgetary concerns.

Under the new law, FDA must identify trends and patterns and provide reports to Congress. It must ensure timely, routine and systematic analysis and reporting. “The situation is more urgent than the timeframes recommended by Congress…Four years after enactment, we hope we can give a dynamite report,” said Woodcock. But she emphasized the need for better analytic tools and that posting information on the web was not as simple as it sounded. Woodcock was pleased with the fact that Congress allowed CDER to form a Risk Communication Advisory Committee, considering the fact that there are limitations on the number of advisory committees the agency is allowed.

Woodcock cited the “new realities in the 21^st century,” alluding to the fact that two decades ago there was a lack of effective treatments for most life-threatening illnesses and today there are more treatments but that a lot of the harm done out in the healthcare system with drugs is through inappropriate and unsafe use. “Congress didn’t pay attention because we didn’t have the tools,” she said. 

The Medwatch program has clearly been inadequate, but perhaps the best the agency could offer at the time, given its lack of technological tools, and its budget and staff.

Woodcock then described a new initiative that is being introduced at the agency, the “Sentinel Concept,” whose purpose is “to ensure drug safety throughout the drug lifecycle by giving equal focus to oversight of drug development and post-marketing safety.” The FDA has made no public announcement to the general public yet about this new concept but will be soon.

The Sentinel Concept will use transactional data such as health claims and electronic health records. The agency plans to partner with data owners to figure out how they can share the information and form a distributed network. “We’ve had tremendous enthusiasm and encouragement from the data owners. There are a tremendous number of pilot projects,” she said.

These pilot projects are being sponsored by private parties that are doing research about how best to set up the system as well as evaluating the feasibility and robustness of analyses.

But there are many issues to be ironed out relating to governance, communication, privacy, access to data and healthcare provider burden that CDER will be addressing over the next six to nine months. Woodcock also expressed the need for the “right mix of staff with appropriate skills” and the need to “work in partnership with the healthcare system.”

But Woodcock stressed that the timing was right. “We couldn’t have done this before because we didn’t have the tools.” She expressed the desire to work in partnership with the healthcare system and remove the tension that has existed between them.

“What we’re dealing with here is uncertainty, uncertainty, uncertainty … We know whatever decision we make, we will be criticized,” concluded Woodcock.

Coast IRB Receives FDA Warning Letter

By Stephen DeSantis

Coast IRB, an independent institutional review board (IRB) based in Colorado Springs, Colo., received a Warning Letter (to see document click here ) from the U.S. Food and Drug Administration (FDA) concerning the company’s improper expedited review of a phase I study being conducted in northern California. In an unusual move, the agency has temporarily suspended the IRB’s ability to do expedited reviews.

Text from the warning letter:

An FDA Warning Letter is quite rare among independent or central IRBs with perhaps one or two issued in a single year. Warning letters to institutional review boards in hospitals or academic settings are more numerous, with the FDA issuing six per year on average.

Coast’s warning letter stemmed from an FDA audit conducted between July 10 and 18, 2007. IRBs are subject to such standard audits every five years. The FDA subsequently reported its inspection findings to the company in a standard Form FDA 483.

“We were surprised to get it. We thought we had adequately responded to the FDA. Obviously the FDA had a different view on that,” said Gary King, general counsel for Coast.

Although Coast stated it has taken steps to minimize any disruption in its business, by adding review boards and holding more frequent meetings, not having the ability to do expedited reviews will no doubt put stress on the company.

“That is going to be a tremendous burden because there is a huge amount of work that is done via expedited review. And these can be as minor as a change of a comma to a semicolon on a consent form,” said David Vulcano, vice-chairman, board of trustees of the Association of Clinical Research Professionals (ACRP). Vulcano has researched IRB issues extensively, including warning letters.

Coast’s responses to that inspection letter were submitted in August and November 2007; however, they have not been made publicly available. According to the FDA, the company failed to address its concerns in their responses, prompting the agency’s action.

MHRA’s New Phase I Accreditation Scheme in Effect Today

By Sara Gambrill

The Medicines and Healthcare products Regulatory Agency’s (MHRA) voluntary Phase I Accreditation Scheme went into effect today with the stated goal of formalizing routine inspections and increasing the scope and depth of inspections. Most importantly, the aim of the MHRA’s new scheme is to avoid harm to trial subjects and for handling medical emergencies during first-in-human trials should they arise.

In the wake of the international media attention that TeGenero received in March 2006 after administering TGN1412 to six healthy volunteers who suffered a nearly fatal “cytokine storm,” the UK in particular has intensely scrutinized how first-in-human phase I trials are conducted and how their conduct could be improved. 

In response to the Duff Report, the European Medicines Agency (EMEA) released a new guidance document on strategies to identify and mitigate risks for first-in-human clinical trials with investigational medicinal products. The guideline went into effect September 2007.

Out of the 22 recommendations made by the Duff Report, three fell under the category of “the clinical environment for first-in-man studies” and two under “developing expertise” on the part of clinical research personnel conducting first-in-human clinical trials.

The final recommendation reads, “The development of a national inspection and accreditation system for clinical centres that undertake first-in-man studies of higher risk agents should be encouraged. The accreditation should be open to all centres that fulfill defined criteria, in both the public and private sectors.”...

Project to Develop Guidelines for Health Research in Africa Launched

By Sara Gambrill

The “Clinical Trials Roundtable” attracted more than 70 participants during the “Science with Africa” conference organized by the United Nations Economic Commission for Africa and the African Union, which is an international organization that promotes cooperation among the independent nations of Africa. The conference was held in Addis Ababa, Ethiopia, and attended by more than 600 representatives, including representatives from health and science ministries, universities, non-governmental organizations and international organizations from Africa, Europe and North America.

Two representatives from industry were also in attendance—Dr. Richard C. Hubbard, senior director, External Medical Affairs, International, Office of the Chief Medical Officer, Pfizer, and a representative from the International Federation of Pharmaceutical Manufacturers & Associations (IFPMA), which represents the global research-based pharmaceutical industry.

Much of the Clinical Trials Roundtable, chaired by Mrs. Avril Doyle, member of European Parliament, focused on identifying the needs of African countries for guidelines in clinical trials and other areas of health research. It also provided an opportunity for leading African and international partners to develop a consensus position on the organization of the project to develop guidelines for health research in Africa.

Francis Crawley, executive director of Brussels, Belgium-based Good Clinical Practice (GCP) Alliance, which he founded in 2005, was approached by organizers of “Science with Africa” in October to participate. Crawley has extensive experience in creating GCP guidelines and model bioethics laws in Eastern European, Asian and African countries. He was also asked to speak briefly at a meeting in the European Parliament in December and subsequently to write an abstract for the roundtable.

More than 70 attended the Clinical Trials Roundtable, which ran for four hours. About 80% of participants were from Africa and the rest were from Europe, the U.S. and Canada, according to Crawley. The industry representatives also participated. At a pre-meeting to the roundtable, African participants made it clear that, despite the existence of many international guidelines, Africa needed its own.

Japan’s New Regulatory Attitude Evident at DIA EuroMeeting

By Sara Gambrill

One of the highlights of the DIA EuroMeeting in Barcelona certainly had to be the update from Japan’s regulatory agency, Pharmaceutical and Medical Devices Agency (PMDA). The session was introduced by Yoshiaki Uyama, Ph.D, a review director at PMDA, who  was wearing a PMDA T-shirt, instead of a suit and tie, which admittedly seemed too casual. He explained that his luggage hadn’t arrived at the same time he had, which produced knowing laughter.

What he went on to say was both surprising and refreshing, coming from a representative of PMDA. He said that he had wondered what he would wear if he didn’t get his luggage in time for the session. In the end, even though he had been reunited with his clothing in time, he decided to wear the PMDA T-shirt to foster an informal atmosphere for the session, which he hoped the audience would find acceptable. This last sentiment was met with an enthusiastic round of applause from the hundreds in attendance, many from big pharma.

Clearly the message PMDA wanted to send during its session was that the agency is striving for openness, cooperation and timeliness to promote Japan’s role in global drug development.

Both Uyama and Satoshi Toyoshima, Ph.D., executive director and director, Center for Products Evaluation at PMDA, discussed many objectives and initiatives to accelerate the drug process in Japan, but the initiative that will have the most immediate impact will launch in April. With the new Investigational New Drug Application (IND) Consultation Process, PMDA wants to increase the number of face-to-face meetings with sponsor companies and also meet with them in a more timely manner.

Uyama noted that in 2006 there were 473 sponsor applications for IND consultations with PMDA, with only 295 actually granted. PMDA wants to increase the percentage of consultations granted to those sponsors that apply and has a tentative plan that Uyama shared with the DIA EuroMeeting audience. From April forward, the new IND consultation process should have a predictable schedule of about five months, during which sponsors are able to submit an expression of intention, apply and submit documents to PMDA.

Five weeks prior to the face-to-face meeting, there will be an inquiry and response period between sponsors and PMDA. Four days prior to the face-to-face meeting, PMDA will give its opinion, which will be discussed at the meeting. Draft minutes will be drawn up and then finalized one month after the meeting.

EDICT Project Opens Policy Recommendations For Public Comment

The EDICT project, short for Eliminating Disparities in Clinical Trials, has invited the public to comment on a series of policy proposals design to help patient recruitment and retention in clinical trials. The period open to public comment runs until March 21.

Shortly after, the final policy recommendations will be brought before the Congress, the National Institutes of Health and the Food and Drug Administration.

Among the issues the policies address are minority participation, patient insurance, informed consent, and standards and accreditation. EDICT is a collaborative alliance between Baylor College of Medicine’s Chronic Disease Prevention and Control Research Center and the Intercultural Cancer Council (ICI). It consists of researchers, public health officials, patient advocates and other various stakeholders.

The four-year project is supported by an unrestricted grant from Genentech.

Ketek Hearing Winners and Losers

By Steve Zisson

After listening to the Feb. 12th hearing by the House Energy and Commerce’s Subcommittee on Oversight and Investigations probing study fraud and the antibiotic Ketek, one thing is clear: PPD, which monitored the study in question sponsored by Aventis (now Sanofi-Aventis), took the least hits from Congress. And it is also quite clear that many in Congress, including committee staff, don’t seem to understand much about the research process.

Outside of the FDA—which the committee would like to hold in contempt of Congress for failing to respond to a subpoena— taking the toughest criticism from the committee was Sharon Hill Price, founder and chief executive officer of Copernicus Group, the institutional review board (IRB) which oversaw the study.

Price, who admitted to being a bit nervous, was hammered by Michigan Democratic Rep. Bart Stupak, chairman of the oversight and investigations subcommittee, and House Energy and Commerce Committee Chairman John Dingell.

Stupak was upset that Copernicus didn’t provide in a timely fashion a call log of a phone call from Ann Marie Cisnernos, the former PPD study monitor and whistleblower, who reported the fraud that led to the conviction of Anne Kirkman-Campbell, a clinical investigator on Study 3014. Price told committee members she doesn’t recall talking to Cisneros.

Visibly frustrated with Price’s answers, Stupak at one point asked Price, “Why do you exist?” Presumably Stupak was referring to the IRB and not Price herself. Many of Stupak’s and Dingell’s questions showed a clear lack of understanding of clinical research. At one point Stupak was baffled at what “GCP” stood for. He was told Good Clinical Practices, the research standard. Ouch.  Dingell seemed lost when trying to figure out where in the research process an IRB figured in.

U.S. Supreme Court Will Not Hear Abigail Alliance v. Eschenbach

By Sara Gambrill

The Abigail Alliance’s petition for a writ of certiorari in The Supreme Court of the United States was denied on January 14. A writ of certiorari is a document which a losing party files with the Supreme Court asking it to review the decision of a lower court.  It includes a list of the parties, a statement of the facts of the case, the legal questions presented for review, and arguments as to why the Court should grant the writ.

The question presented was “whether terminally ill patients who lack alternative treatment options have a constitutional right to purchase unapproved investigational drugs that have not been shown to be safe or effective and that have not been authorized for treatment uses by the Food and Drug Administration.”

Industry insiders as well as many terminally ill patients believed that if Abigail Alliance had won its suit that it would wreak havoc on the drug development process and how it is regulated.

In August 2004, Judge Ricardo Urbina of the U.S. District Court for the District of Columbia granted the government’s motion to Abigail Alliance’s original lawsuit, which was filed on July 28, 2003, on the ground that the FDA policies do not violate the rights of patients. Abigail then won its suit on appeal in a 2-1 decision handed down by a three-judge appellate panel in the U.S. District Court for the District of Columbia in May 2006.

FDA then appealed in July 2006 for a re-hearing before all the judges of that court on the grounds that the May 2006 decision presented a serious threat to FDA’s ability to ensure the safety and effectiveness of prescription drugs sold in the U.S. The re-hearing was granted in November 2006 and the case was argued in March 2007 and decided in August 2007...

HHS Report Criticizes FDA’s Human Subject Protection Efforts and Lack of Site Audits

By Steve Zisson

The U.S. Food and Drug Administration (FDA) audited fewer than 1% of investigative sites, the inspector general of the Department of Health and Human Services (HHS), Daniel R. Levinson, found in a report released Friday.

The 41-page report said the FDA has just 200 specially-trained inspectors to audit an estimated 350,000 investigative sites. Others estimate that the number of sites is much lower.

The report found that federal health officials did not even know how many clinical trials were being conducted in the U.S. According to CenterWatch, an estimated 59,000 drug trials, phases I, II and III, were being conducted worldwide in 2006.

The Office of Inspector General (OIG) investigated after receiving a congressional request to review FDA’s oversight of clinical trials  a series of news articles highlighted vulnerabilities, the OIG report said. “The series identified problems with FDA’s oversight of clinical trials, including insufficient informed consent procedures, inadequate training and certification requirements for IRBs, limited Federal regulations, and FDA’s failure to enforce existing regulations,” the OIG report added.

The report said FDA “views its protocol review before a clinical trial commences as the most important step in protecting human subjects. We recognize the important role that FDA’s protocol review plays in protecting human subjects and made several changes to our report to reflect this point. We do note, however, that this report addresses another important part of the system for protecting human subjects: oversight of the trials once they are actually underway.”

Levinson’s report said that when those overburdened inspectors found serious problems in clinical trials, their superiors in Washington downgraded their findings 68% of the time. And the report found that in the remaining cases, the FDA almost never followed up with inspections to determine whether the corrective actions that the agency specified had been done.

“The report issued today by the Department of Health and Human Services Office of Inspector General offers valuable insight into FDA’s program to protect clinical trial participants. The agency agrees with the report and is already acting on all its recommendations. Volunteers play a critical role in making treatments available that help millions of patients and FDA is committed to ensuring strong oversight to protect participants,” said Heidi Rebello, spokesperson for Office of the Commissioner at the FDA.

As its mission has grown, FDA has been widely criticized as underfunded in numerous areas beyond clinical trials, such as drug importation and food safety.

The HHS’ inspector general found the FDA disqualified investigators from conducting clinical trials 26 times from 2000 to 2005 and disqualified their data only twice even though the agency found serious problems at trial sites 348 times during that period.

The inspector general also recommended that the agency create a registry of continuing clinical trials, launch a registry of research ethics boards, build a database to track its research inspections and get more authority to regulate research assistants.

OIG identified five steps that could take to improve its system of oversight:

• Develop a comprehensive internal database of all clinical trials,
• Create a registry of IRBs,
• Create a cross-center database that allows complete tracking of FDA inspections,
• Seek legal authority to provide oversight that reflects current clinical trial practices; and
• Establish a mechanism to provide feedback to FDA district office staff on their inspection reports and findings.

Read the OIG report here.

Steve Zisson, managing editor of Thomson CenterWatch.

Congress Passes Long Awaited PDUFA Renewal Act

The U.S. House and Senate passed the long awaited FDA Revitalization Act, a five-year renewal of the Prescription Drug User Fee Act of 1992 (PDUFA). PDUFA allows the FDA to collect fees from drug and device companies applying for regulatory approval. That law was set to expire on Sept. 30.

The new bill calls for an increase in those submission fees to bolster FDA’s drug safety review and monitoring activities. Under the bill, pharmaceutical developers would pay nearly $400 million and medical device makers $48 million in fees next year, a 25% increase.

However, the bill would go much further than its predecessor. The proposed law will grant the FDA much more oversight on treatments already approved and give teeth to the agency in enforcing rules that have been ill-defined the past.

The bill would enhance the government’s clinical trial registry (clinicaltrials.gov) by making studies posted there conform to the international standards developed by the World Health Organization. Written into the bill are regulations that require drug developers to publish all clinical trial results used to obtain a drug’s approval, including any trial results used by the review committee, which reviewed the product, and any trial conducted after the product has been approved.

The law would also give the FDA the ability to impose fines on companies that do not conduct any additional studies that the agency mandated upon granting an approval. Historically, these post-approval studies were not tracked. The bill also calls for a generic drug database, a litigation clauses and orphan drug provisions.

A link to the bill can be found here.

China and India Join WHO Registry Database

China and India have joined a World Health Organization (WHO)-run international database of clinical trials. Both countries had already recently established their own databases but had to align those registries with a set of standard criteria set forth by a team of experts at the United Nations.

The database was established following an international summit on transparency in Mexico City in November 2004.

“Access to information about ongoing, completed and published clinical trials is essential for informed decision-making. Researchers, research funders, policy-makers, medical practitioners, patients and the general public need such information, to help guide research or to make treatment decisions,” stated the International Clinical Trials Registry Platform (ICTRP) web site.

The WHO is currently evaluating at least eight additional registries, including those from South Africa and Hong Kong. According to published reports, Germany and Brazil are also attempting to join the group. The U.S. is already submitting trials from its registry, clinicaltrials.gov.

The WHO clinical trials registry site can be found here. (http://www.who.int/trialsearch)

AAHRPP Accredits 16 New Research Organizations

By Stephen DeSantis

The Association for the Accreditation of Human Research Protection Programs (AAHRPP) has accredited its largest group of institutions at one time in its six-year history. In total, 16 organizations gained AAHRPP approval. The certification is valid for three years. The AAHRPP is a non-profit organization that offers accreditation to organizations that conduct or review research with humans.

“This is the largest number of accreditations we have awarded at one time and we expect the numbers to continue to grow as we see an ever-expanding list of applicants, said Marjorie Speers, Ph.D., executive director of AAHRPP.

The list of hospitals or health systems that received full accreditation includes the Cincinnati Children’s Hospital, The MetroHealth System in Cleveland, Ohio and the University Hospitals Case Medical Center in Cleveland. Among the list of universities were: University of Cincinnati, University of Kentucky, University of Utah, University of Rochester, University of Southern California, and the Virginia Commonwealth University.

Three Veterans Administration facilities were granted full accreditation, including Cincinnati Department of Veterans Affairs Medical Center, the Department of Veterans Affairs Salt Lake City Health Care System, the Veterans Affairs Pacific Islands Health Care System in Honolulu; VA Palo Alto Health Care System and  Veterans Affairs Healthcare Network Upstate New York at Albany. Austin, Texas-based IntegReview Ethical Review Board also received full certification.

Lexington VA Medical Center received qualified accreditation, which means it met the standards with only a few minor deficiencies in administrative processes, not involving patient care. It will still be accredited for three years and if these deficiencies are corrected within that time, the institution will receive full accreditation status.

“This is a very exciting time for these organizations and for AAHRPP. Not only is it a significant achievement for these institutions, but accreditation is critical for the public’s trust in research,” added Speers.

AAHRPP has accredited 68 organizations since 2001 and is currently working on nearly 400 new accreditation assessments.

Stephen DeSantis is the Senior Associate Editor at Thomson CenterWatch.

MDS Reports Strong Growth in Late Stage Business

MDS had a big second quarter following the sale of its diagnostic business and the life sciences company is also encouraged by signs of a turnaround in its MDS Pharma Services unit’s late stage business.

The Toronto-based company reported net income ballooned to $736 million or $5.34 a share compared with $14 million or 10 cents in the second quarter a year ago. Earnings included a gain of $792 million from its diagnostics unit sale. The overall company’s revenue jumped 13% to $273 million compared with $242 million in the year ago quarter.

In its second quarter, MDS’ revenues from the company’s late stage segment grew 22% to $55 million. The company’s early-stage segment was down 12% compared with the year ago quarter, partly due to U.S. Food and Drug Administration (FDA) issues at its Montreal site. MDS stated it expected to have the majority its independent audits completed by the end of the year, at a cost of $61 million to the company.

Second quarter revenues from the company’s analytical technologies division rose 54%, compared with the same period last year. Those earnings included results of its Molecular Devices acquisition in March 2007.

“I am pleased that we continued to make solid progress executing our strategy,” said Stephen DeFalco, president and chief executive officer of MDS. “I am encouraged by the steady improvement.

In February 2005, MDS agreed to conduct a review of all it bioequivalence studies done at its Ville St. Laurent, Quebec site. The review covered a five-year period from January 2000 through December 2004. This was done in response to FDA concerns about the company’s bioanalytical testing operations after a routine inspection in 2003.

MDS Pharma Services also recorded a $26 million charge to restructure and streamline its business. It will use these funds to “optimize” its global network through site consolidations, workforce reductions, and operational enhancements.

Senate Okays PDUFA

By Stephen DeSantis

In a 93-to-1 vote, the U.S. Senate has approved a bill re-authorizing the U.S. Food and Drug Administration (FDA) to collect fees from drug companies to review investigational new drugs. The bill would also require that all phase II and later stage trials for both drugs and devices be listed on the government’s web site, www.clinicaltrials.gov.

Currently, the listing of trials beyond those for serious and life-threatening conditions is voluntary from a regulatory perspective. In addition to listings, the bill requires trial results to be added to the database after a product has been approved for marketing. The trial results will be provided by the FDA, the National Institutes of Health and peer reviewed journals. Sponsors who violate the new laws will be subject to monetary penalties.

The Prescription Drug User Fee Act (PDUFA), which was originally enacted in 1992 and was set to expire on Sept. 30, increases the amount collected through PDUFA by $138 million a year. The bill was sponsored by Sen. Edward Kennedy, D-Mass., chairman of the Health, Education, Labor and Pensions Committee and Sen. Michael Enzi, R-Wyoming, a ranking member of the Senate Health, Education, Labor and Pensions Committee.

Although the bill would mean higher costs per drug submissions and force transparency on the pharmaceutical industry, it had the support of its largest lobbing group. The Pharmaceutical Research and Manufacturers of America’s (PhRMA) president and chief executive officer, Billy Tauzin, said in a statement:

“Swift reauthorization of the Prescription Drug User Fee Act (PDUFA) is essential to ensure that the Food and Drug Administration (FDA) has the resources necessary to protect and promote the public health. To this end, PhRMA applauds the Senate’s quick passage of the PDUFA legislation.”

Stephen DeSantis is the Senior Associate Editor at Thomson CenterWatch.

Cancer Biomarkers Collaborative Formed

The American Association for Cancer Research (AACR) has formed a collaborative group with the U.S. Food and Drug Administration (FDA) and the National Cancer Institute (NCI) called the Cancer Biomarkers Collaborative (CBC). The purpose of the CBC is to champion the use of validated biomarkers in clinical trials.  Its mission is to develop a set of guidelines for effectively integrating predictive biomarkers into oncology trials.

"Major advances in cancer biology over the last quarter century have provided us with a better fundamental understanding of cancer in all of its forms, yet the translation of this knowledge into medical practice remains painstakingly slow," said William Hait, M.D.,Ph.D, president of the AACR.

The group will meet this summer to begin discussions on how to develop specific guidelines.

CMS Seeks To Revise Clinical Trial Coverage Rules

By Stephen DeSantis

The Centers for Medicare and Medicaid Services (CMS) has proposed new coverage rules for payments to Medicare recipients involved in clinical trials. The rules would revise the agency’s Clinical Trial Policy’s national coverage determination (NCD) system and push additional transparency requirements on trial sponsors.

Some of the new rules would include adding post approval study coverage,requiring all studies to be registered with the NIH’s clinicaltrials.gov web site prior to enrollment, requiring all studies to publish results and paying for additional clinical services outside of the trial. The proposal also seeks to rename the coverage policy, the Clinical Research Policy. The new rules will be open for comment for a 30-day period after which the CMS will review these suggestions and draft a final NCD within 60 days.

“This new decision will signal our continued support to provide access to services for beneficiaries by facilitating participation in the full range of qualified, scientifically sound research projects,” said Leslie Norwalk, acting administrator for CMS.

The full draft of the proposed policy changes and the current rules for the NCD system can be found on the CMS website.

Stephen DeSantis is the Senior Associate Editor at Thomson CenterWatch.

EMEA Tightens Phase I Guidelines

By Stephen DeSantis

The European Medicines Agency (EMEA) has drafted guidelines to help ensure the safety of subjects enrolling in first-in-man studies. The guidelines come on the heels of TeGenero’s trial, which caused six otherwise healthy phase I subjects to suffer severe adverse reactions after being administered an immunological agent at a hospital in the United Kingdom. Following the incident, reviews were performed on how the study was conducted and concluded it satisfied current regulatory requirements. Among the many items cited in the report, the EMEA recommends that the Minimal Anticipated Biological Effect Level—or MABEL—be used when testing “high risk products” such as monoclonal antibodies in phase I trials.

The draft is open to a two-month public-consultation period, after which the EMEA will hold meetings with industry, academic researchers, regulatory bodies and healthcare professionals to hear feedback. The final guidance will released following that process.

You can access the draft guidelines in .pdf format here.

Stephen DeSantis is the Senior Associate Editor at Thomson CenterWatch.

Rigorous Clinical Trials Proposed for Generic Biologics

by Steve Zisson

There was encouraging news coming from testimony about legislation proposed for regulating generic biologics before the Senate Health, Education, Labor, and Pensions committee on Thursday.

The committee is beginning to understand the importance of having a full round of rigorous clinical trials for any generic biologic. Manufacturing a biologic isn’t like stamping out a new batch of pills. It is immensely complicated work where inexperienced companies should have to go through stringent clinical trials.

This is good news for patients and their safety and for the biotech companies that have spent millions on developing new biologics.

It is also good news for the pharmaceutical outsourcing industry and contract research organizations such as Parexel, PPD, PRA, ICON, Covance, PharmaNet, Quintiles and others. They will benefit from the projected increase in clinical trials and from their push in the last few years to work with biotech companies. In the short term it could be welcome news for biotech giant Amgen, whose anemia drug Epogen goes off patent in six years...

Progress On Clinical Results Transparency

Posted by: Sara Gambrill

Since the International Committee of Medical Journal Editors (ICMJE) announced in September 2004 that it would consider for publication an article about a research project only if it was posted to a central registry before September 13, 2005, pharmaceutical companies have committed significant personnel, time and money to the issue of clinical trials transparency. And their efforts are paying off.

According to an editorial published recently in the New England Journal of Medicine, only 8% of clinical trials listed in the first 11 months of 2006 on clinicaltrials.gov, the National Institutes of Health’s registration web site, had incomplete information, compared to 26% of trials listed before 2006.

Thomson CenterWatch estimates that industry spending on trial registries will continue to rise. In 2005, the top 15 biopharmaceutical companies spent $89 million for various efforts to disclose clinical trial information, and CenterWatch estimates that they will spend $97 million this year...

Going To The Dogs

Posted by: Steve Zisson

In a week when the feds cracked down on some of those quick-loss diet companies with hefty fines for making false claims about their untested pills, it seemed just a bit odd that the FDA approved the first diet drug for dogs.

I can’t blame Pfizer Animal Health for going after this huge and growing market with Slentrol. There are about 62 million pet dogs in this country and more than 20 million are considered overweight or obese. I’d bet the very same owners of those 20 million dogs fit into those overweight and obese categories. Might be a good opportunity for Pfizer to cross-sell to the owners.

In a country where dog owners treat their animals as if they were their “babies”, it’s no surprise that their dogs are out-of-control eaters because most owners don’t train or control their dogs at all. Just watch an episode or two of the dog training show “Dog Whisperer” and see host Cesar Millan time and time again have to give owners basic dog training. His show should be mandatory for all new dog buyers...

Radical Thinking On Oncology Funding

Posted by: Sara Gambrill

A deputy director from the National Cancer Institute (NCI) has proposed a radical overhaul of the way NCI allocates oncology clinical trial funding. His proposal would eliminate disparities in oncology clinical trial participation and health outcomes resulting from differences related to race, ethnicity and income. Dr. Jon Kerner, who works in the Division of Cancer Control and Population Sciences, shared his ideas at a recent roundtable held at Baylor College of Medicine.

Typically, only 3% to 5% of cancer patients participate in oncology clinical trials, a low percentage that slows down the drug development process. Most discussions about eliminating disparities in clinical trials focus on increasing the number of cancer patients among racial and ethnic minorities, but not on the overall percentage of cancer patients participating. So, more racial and ethnic minorities could participate, but the rate of cancer patient participation would still remain abysmally low.

Kerner has asserted that what’s actually needed to increase minority participation, overall participation and advance science is inclusion of 100% of all the patients who have the cancers that meet his three criteria: scientific opportunity, distinct disparity in terms of who gets them and/or who dies from them and high fatality rates...

India Needs More IRBs

Posted by: Lisa Marie Castro

Pfizer announced on December 5th that it was pulling the plug on torcetrapib, an investigational drug that raises “good” cholesterol and reduces plaque buildup in blood vessels that can cause heart attacks.

Pfizer had made an investment of nearly $1 billion on the development of torcetrapib. The investigational drug was three years into phase III clinical trials and had enrolled 15,000 patients. When more torcetrapib-related deaths than acceptable were identified by a Data Safety Monitoring Board after it had reviewed trial results, the 100 hospitals and medical clinics in three continents where the study was being conducted were notified to halt the study.

As India becomes increasingly preferred as a destination for the outsourcing of clinical trials, issues of informed consent and safety will become more significant. It is estimated that there are over 80 hospitals (government and privately owned) actively engaged in global and local clinical trials. Those numbers are expected to double or even triple each year by 2010, with 14,000 hospitals in the country...

The FDA On Madison Avenue

Posted by: Steve Zisson

The Food and Drug Administration (FDA) has a deal in place that for the first time would allow pharma companies to pay fees for the FDA to review their drug advertisements. It is all being done in the hope of faster reviews. It’s not such a bad idea.

But I’ve got another idea to take it a step further that would help speed up review of drug advertising. Put together a citizen panel to check these ads before they go on air. We’ve all seen television ads for numerous new drugs, particularly the lifestyle drugs, that are simply laughable. The FDA can’t legislate good taste, I suppose, but maybe it should.

And many don’t believe some claims being made in a number of these advertisements. You’ know what I’m talking about - you’re in the middle of watching a football game, one of these ads comes on and everyone starts cracking jokes about it. One look at a proposed ad by a citizen panel would get an immediate reaction and give the FDA the feedback they really need. FDA staffers may not to able to really see an ad from the point of view of the public since they are dealing with the industry every day. The view from inside from a federal agency can get insular.

Pharmaceutical companies are expected to pay up to a $50,000 fee to the FDA for each TV ad campaign review. Throw a little more in the pot to set up a citizen panel, and the FDA and Madison Avenue may get better results.

Steve Zisson, managing editor of Thomson CenterWatch.

FDA Proposes New Regulations for Expanded Access to Investigative Drugs

The U.S. Food and Drug Administration (FDA) has submitted two regulatory proposals that would expand the rules concerning who has access to investigative treatments. The new proposals would provide a clearer pathway for certain critically ill patients so they can be considered for access to investigative drugs without enrolling in a clinical trial.Both proposals have been submitted to the Office of Management and Budget (OMB), where they will be reviewed for approval.

If the FDA’s two proposals clear the OMB review process, they would be released for public comment before taking effect.

Don’t Be Outfoxed By Dems' Win

Posted by: Steve Zisson

The Democrats’ decisive victory in Tuesday’s mid-term election put them in control of the House, but it is widely seen as bad news for the pharmaceutical industry. Dire predictions of drug price controls have many in big pharma concerned. Pharma should be worried—especially if it sticks to the old game plan.

But the Democrats’ moves against the drug industry are not likely to be as drastic as warnings suggest. So long out of power, the Democrats don’t want to revert to their old ways and to be seen as the anti-business party. They have a chance to take the middle road where they can be perceived as both pro-business and pro-consumer...

Can EU Regulators Keep Up with Innovation?

Posted by: Sara Gambrill

The now infamous TeGenero clinical trial - six patients fell critically ill from an investigational biologic — occurred, ironically, after the EU Clinical Trials Directive had been implemented in the UK in May 2004. Biotechs in the Netherlands, it seems, were adjusting to the adoption of the EU Clinical Trials Directive into national law on March 1, 2006 when the TeGenero incident occurred (March 13). Before that, healthy volunteer trials in the UK had been unregulated.

At the recent Applied Clinical Trials European Summit in Amsterdam, one speaker talked about the long shadow the TeGenero trial will cast not only on the Netherlands but on the entire European Union. Even though the Medicines and Healthcare Products Regulatory Agency’s (MHRA) final report from May identified some Good Clinical Practice discrepancies, the main cause of the severe reactions in the six trial volunteers was an “unexpected biological effect.”...

Terrifying Budget Numbers

Posted by: Steve Zisson
 
For all that consumers expect from the U.S. Food and Drug Administration, it is completely irresponsible of the federal government to fund it with less than $2 billion a year. By comparison, that’s exactly the same dollars the federal government is spending each week on the war in Iraq.

Now some in Washington would argue that spending $2 billion a week on the war in Iraq is central to fighting the war on terror. But the FDA is also on the front lines of protecting the American people from terrorist threats against our food and drug supply. With the latest E. coli scare in the news, it became clear that the FDA does not have the resources for that particular fight to protect our citizens.

Disapproving Look

Posted by: Steve Zisson

Well, it’s about time the FDA took a hard look at the compounding of drugs at some pharmacies. Until now, the FDA sort of looked the other way at pharmacists who custom-blended drugs from bulk ingredients. Particularly popular have been custom hormone replacement therapies or drugs that remove an ingredient that may be an allergen.

Wyeth has been wanting the FDA to step up to the plate with tighter regulations. Of course, Wyeth has a drug that competes with some of these special blends of hormones. On the other side, pharmacists in Texas have argued that the FDA shouldn’t treat custom blends as unapproved new drugs, even if the pharmacists have been touting their blends as safer than the approved drugs.
If they want to make those kinds of claims about the safety of the drugs they are blending, then they better think about conducting some expensive clinical trials to prove it.

Steve Zisson, managing editor of Thomson CenterWatch.

The Right To Use Unproven Treatments?

Posted by: Sara Gambrill

It’s ironic that at a time when several high-profile marketed drugs have been given a black box warning or withdrawn from the market that the Abigail Alliance has gathered steam.

The Abigail Alliance is a patient advocacy group that is suing the U.S. Food and Drug Administration for the patients’ “right” to take an experimental drug after it has been through only one phase of drug development. Two members of the three-judge panel of the U.S. Court of Appeals for the D.C. Circuit found that patients with a life-threatening and otherwise untreatable disease have a constitutional right to seek experimental treatments, even if researchers have not determined efficacy. In addition, the court said that the government should be removed from the equation unless it has a “compelling interest.”

Trial Registries Proliferate: Is Anyone Benefiting?

Posted by: Dan McDonald

The issue of clinical trial result transparency continues to evolve at a rapid pace. During the past few years, almost every stakeholder has taken action in some form.  This should be a positive development because there is a lot attention being focused on a very important issue. But at the end of the day, have we made a difference? Has the noise that this caused just confused the issue more for patients and physicians, or made finding trial information easier and more useful?

The fact is patients today have to navigate a world of disparate databases with listings written in difficult medical terminology and formatted in different ways in order to find trial information. The creation of some clinical trial search engines might help the patient find trials faster, but the search results simply link you to the different registries so the same problem remains. The industry has spent nearly $100 million during the past 24 months to respond to the outcry from advocacy groups, government agencies and professional associations to be more transparent with information about their active and completed clinical trials. But, are we any better off as a result?

British TaskForce Submits Recommendations for Phase I Guidelines

Posted by: Stephen DeSantis

The Association of the British Pharmaceutical Industry (ABPI) and the BioIndustry Association (BIA) taskforce has established recommended guidelines to enhance patient safety in phase I studies with novel agents. The taskforce was created to address safety concerns following the events during the TeGenero trials with the immune stimulate TGN1412...

Super-Size The FDA

Posted by: Steve Zisson

A proposal in Congress to boost funding for the FDA makes a lot of sense. But don’t stop there, Congress - a super-sized FDA would help solve many of the issues around drug safety. Make sure it’s truly independent, though, and free from pressures from the pharmaceutical industry, brought upon it by a lack of resources. Drug research reformists often suggest creating an independent clinical trials agency to perform trials for the industry, but that’s a far-fetched and unworkable solution.