New England Research Institutes Partners With Evidence

Watertown, Mass.-based CRO New England Research Institutes (NERI) established a strategic partnership with Evidence Clinical and Pharmaceutical Research Institute, a CRO which focuses on conducting trials in Russia and Eastern Europe. Evidence is headquartered in Saint-Petersburg, Russia, and has offices in Los Altos, Calif., and Swampscott, Mass. The companies stated that both Eastern Europe and Russia are becoming increasingly popular regions for conducting clinical trials, and sponsors are creating an ever larger presence there.

“In addition to our North American depth, we have established a consortium of strategic CRO partners in emerging locations. The Evidence team fits well within our mix of employees and partners because they offer excellent data quality, high recruitment rates, well-trained and experienced personnel, and advanced communication technologies,” stated Rebecca Li, Ph.D., NERI’s vice president of clinical research.

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.

Revolutionary Public-Private Partnership for Early Phase Trials Established in France

By Sara Gambrill

The Centre Hospitalier Universitaire (CHU) de Caen, a university teaching hospital and the largest hospital in the West of France, and Therapharm, a large, private contract research organization founded in 1980, have joined forces to form the first public-private partnership to conduct early phase clinical research in France. The clinical research center is called Centre de Recherche Clinique-Basse Normandie (CRC-BN). The center conducts phase I and II clinical trials that are industry-sponsored, investigator-initiated and government-sponsored.

Antoine Cournot, who is president of Therapharm and spearheaded the partnership, said, “The objective of the clinical research center is to be able to perform early phases, phase I and II, with a high level of international quality but with a professional approach.”

The impetus for the unique partnership was to attract more industry-sponsored clinical research to France. Creating a public-private partnership clinical research center in a large hospital has been a dream of Cournot’s for 20 years, when he first attempted to establish one in Paris, where Therapharm’s headquarters are. Ten years ago, when Therapharm moved its phase I unit from Paris to Caen—in close proximity to CHU de Caen—Cournot approached the hospital about his idea.

But, it wasn’t until 18 months ago that the hospital and Therapharm met for a serious discussion about plans for building CRC-BN...

Nevada Doctor Reports Cherie Thibodeau to Attorney General’s Office

By Sara Gambrill

Cherie Thibodeau, a fraudulent study broker, may not be working her scam much longer.

For the past few months, she has been trying to solicit Las Vegas area doctors for business, using a business card that says, “Cherie Thibodeau, M.D., PhD., Chief Medical Officer/Clinical Operations.” As far as can be determined, Cherie Thibodeau does not have a license to practice medicine, and posing as someone with a medical license is an offense that is under the jurisdiction of the Attorney General’s Office in Nevada.

One Nevada doctor, whose confidence Thibodeau gained, reported her to the Attorney General’s office last week.

Off and on between stints in California State Prison, Thibodeau has operated under several aliases, including Cherie Casio and Cherie Rivard, and last year, started claiming to have a medical degree. During the six years that CenterWatch has been reporting on her activities, Thibodeau has bilked numerous investigative sites across the U.S. out of potentially hundreds of thousands of dollars.

CenterWatch obtained a copy of a solicitation letter from an alert reader who recognized Thibodeau’s name from previous articles in CWWeekly and The CenterWatch Monthly. That letter was sent by “Cherie Thibodeau, M.D.” and “Dr. X” to Las Vegas area doctors on Oct. 3, 2007. The letter states that “Doctor X” has been selected to participate as a principal investigator in a phase IIa post-herpetic neuralgia clinical trial and is looking for “consulting physicians who are interested in referring patients who meet criteria for the study and enroll as possible participants.” Thibodeau promises compensation to doctors for patient referrals, which is unethical according to Good Clinical Practice.

Dr. X became suspicious of Thibodeau during the site review when she gave the monitor a different name  than the doctor knew her by—Cherie Casio. When Dr. X asked her about it, Thibodeau claimed that Casio was her maiden name and that she preferred to use it.

Thibodeau’s typical scam is to promise doctors that she will get them studies and handle administrative tasks for a percentage of the study budget. All payments go through her. Thibodeau starts off paying sites their fair share or enough of it for the first one or two studies and then pays them nothing and can’t be reached. Lately, she’s paid sites nothing at all, defrauding them of funds due them. Most recently, she bilked a site in Ohio out of $5,000.

Sara Gambrill, Senior Editor at Thomson CenterWatch and author of The Emerging Markets of Clinical Research.

Michael J. Fox Foundation Gets It and Gets It Done

By Steve Zisson

The Michael J. Fox Foundation (MJFF) for Parkinson's Research gets it. They have figured out just how many bottlenecks there are for getting good research out of academia and to the patient. And Michael J. Fox is willing to put its money where it is needed to move along the drug development process.

It is no small task, but MJFF is headed in the right direction. The foundation has awarded $95 million for Parkinson’s disease (PD) research since its founding in 2000. Last week, MJFF kicked off its 2008 Target Validation effort. Under this annual program, the foundation will award up to $2 million for projects designed to “validate the therapeutic potential of scientific discoveries, pushing them one step closer to possible pharmaceutical industry investment and clinical trials.”

Maybe the most interesting step the foundation took this year is to enlist contract research organizations (CROs) in its efforts for the first time. The foundation and many observers understand that discoveries will be a long time in coming to clinical trials if everything is left up to academics.

MJFF has identified several CROs to help applicants gather critical information essential for ensuring studies are appropriately designed to validate or invalidate targets, such as dosing amounts and brain bioavailability.

Grant submissions must include the necessary pharmacokinetic and toxicology studies required to fully validate their targets, and the Request for Applications (RFA) includes a list of CROs equipped to perform these studies.

For investigators who are not able to carry out the required test in their own labs, MJFF has identified several CROs to help applicants gather this critical information. The expertise and resources provided by the CROs will allow awardees to obtain information critical to fully validating the proposed targets.

"Target Validation is emblematic of our Foundation's aggressive, 'get-it done' approach to driving PD drug development and speeding delivery of treatments that can improve patients' quality of life," said Katie Hood, interim chief executive officer of MJFF.

"Target Validation has a single purpose: to definitively assess the importance of promising targets by proving or disproving their druggability. This is a vital component of the Foundation's strategy to accelerate the pace of drug development by reducing industry's risk around investing in potential PD treatments."

Target Validation 2008 specifically seeks investigator-initiated applications to demonstrate that modulation of a specific cellular target (such as a gene or protein) results in a PD-relevant therapeutic response in an appropriate whole-animal mammalian model of PD. Of particular interest are targets whose manipulation holds the potential to treat the symptoms of PD, including both 'motor' and 'non-motor' symptoms such as cognitive dysfunction, autonomic dysfunction, sleep disorders and depression.

Also of interest are targets that could be used to protect or restore degenerating neurons, as well as those that can treat complications of current PD treatments (e.g., dyskinesias).

Target Validation pre-proposals are due by Dec. 18, 2007 and funding is anticipated by spring 2008.

A conference call with MJFF Research Programs staff to further clarify the aims and goals of this initiative will be held Nov. 27 at noon U.S. Eastern Time. Researchers wishing to participate in the call must RSVP to conferencecalls@michaeljfox.org and will receive an e-mail reply with call-in details.

Steve Zisson, managing editor of Thomson CenterWatch.

NEJM Takes Shots at CROs

By Stephen DeSantis

A recent New England Journal of Medicine (NEJM) Perspective piece criticized the clinical trials industry for its reliance on contract research organizations (CROs). The piece describes the rapid growth in the CRO industry, questions the quality of research data it generates and cites various clinical trials that have shed some negative light on CRO-run studies.

The article “Commercializing Clinical Trial–Risks and Benefits of the CRO Boom” was written by Miriam Shuchman, M.D., a NEJM national correspondent.

“Given the steady dominance of CROs in the clinical trials domain, the current flaws in the model will need to be remedied. This will require some shift in focus–less single-minded attention to ‘deliverables’ and ‘billable hours’ and greater concern with the discovery of new knowledge,” concluded Shuchman.

Shuchman was unable to be reached for comment at the time of publication.

In the article, Shuchman references two now well-known examples involving CROs: the TeGenero monoclonal antibody study conducted by Parexel in England and the Aventis (now Sanofi-Aventis) trial for the antibiotic Ketek performed by PPD. In both cases, the CROs were found to have acted appropriately and well within regulatory requirements.

Another major point of contention with Shuchman is the industry’s apparent focus on speed and cost-efficiency as opposed to quality data. She notes that CROs have gradually taken over much of the role formerly done by academic institutions.

Doug Peddicord, director of the Association of Clinical Research Organizations (ACRO), strongly disagreed with Shuchman’s criticism of CROs compared with academic centers.

“There is certainly no research that we are aware of that suggest that the number of 483s [FDA Form 483–Notices of Inspectional Findings] or other indicators of difficulties with GCP [Good Clinical Practice] compliance are any different between those two settings,” said Peddciord.

She cites a Tufts Center for the Study of Drug Development report that found CRO-managed projects showed fewer delays than projects that did not use CROs. The 2006 Tufts report also found that those studies did not show a decrease in research quality.

Schuchman went on to question that premise. ACRO’s Peddicord found her argument puzzling.

“To cite a sourced article that says that CROs usage improves the speed of the development process without diminishing the quality of the research and then to go on, in essentially the same sentence, with an unsubstantiated statements from anonymous ‘others’ doesn’t follow basic standards of evidence and is problematic,” he said.

Among myriad of other issues she cites in the piece is that CROs have a high staff turn-over rate during clinical projects, causing the their workforce to be “younger, less skilled, less experienced and less educated” than at pharma companies or within academia.

“Actually, pharmaceutical, biotechnology and CRO employees are drawn essentially from the same personnel pool. And we’re seen a high degree of cross-sector movement all around in recent years,” stated Peddicord. He said the personnel turnover is due to a severe shortage of clinical professionals in both industry and academic institutions, putting experienced workers in high demand.

“There are fewer skilled investigators, skilled monitors and skilled research coordinators than the whole drug development enterprise needs,” he said.

Shuchman suggested that although an alternative model, academic research organizations (AROs), “avoid some of the workforce and qualification problems,” they must compete with CROs for contracts which add pressure to the institutions to conform to sponsor study designs.

According to CenterWatch data, there are few AROs of any size and only one, Duke, that has some ability to conduct the kind of large global clinical trials that are required today. While there are more than 1,000 CROs worldwide, only about a dozen of the largest can conduct trials globally.

“One of the things that we certainly reacted to, in terms of the perspective piece, is the assertion that this kind of specialized expertise has begun to ‘kill clinical research.’ It was absolutely unwarranted and there is no empirical data provided within the article to support that claim,” said Peddicord.

Fraudulent Study Broker Cherie Thibodeau Continues to Bilk Sites

As a public service to sites, CROs and biopharmaceutical companies, CenterWatch is posting a long excerpt of this week’s CWWeekly article about fraudulent study broker, Cherie Thibodeau.

If you have been defrauded of funds by Cherie Thibodeau, please contact CenterWatch at cw.editorial@thomson.com.

By Sara Gambrill

Cherie Thibodeau, who operates under multiple aliases and claims to be an M.D. in her solicitations to investigative sites, CROs and biopharmaceutical companies, has bilked at least one more site out of almost $5,000 since CWWeekly published its last article about Thibodeau in February.

In the latest case, Thibodeau sent a solicitation by fax last October to Partners in Research, LLC, an Akron, Ohio-based site, to which it responded. Thibodeau followed up with a telephone call about a diabetes study study sponsored by Novartis, and within two weeks, the site was chosen to participate in that study, according to Colin Moorhead, M.D., president of Partners in Research.

Some of the terms of the agreement that the site signed with Thibodeau, who was listed as Dr. Cherie Thibodeau, M.D., Ph.D.,” were that she would handle administrative tasks, such as regulatory documentation, marketing and advertising, for the site. For that work, she would take 10% of the revenue from any study she brokered for the site and the same percentage for any study the site was able to get on its own. But after months of working on the initial study, the site had not received reimbursement from Thibodeau, even though she had been paid by the sponsor.

“Around February, it was starting to get hard to get a hold of her or get her to respond…We’ve already had a couple of patients screened and a patient enrolled in the [diabetes] study and we’re wondering when do we expect some reimbursement?” said Moorhead.

Partners in Research continued to conduct the study and a few months later, the site was able to get a study on its own from Merck...

Cost of Compliance Rising for AHCs

By Stephen DeSantis

The Association of Academic Health Centers (AAHC), a non-profit organization supports the nation's academic health centers, has released a paper reporting that its members are allocating higher amounts of funds towards increasingly burdensome clinical trial compliance requirements. The AAHC placed investing in compliance as its top priority and called the requirements essential for ensuring safe and effective trials. However, the AAHC stated the cost of compliance is a national issue facing the entire academic health center (AHC) enterprise. The report said that for a one-year period, some AHCs reported compliance costs increased as much as 70%. The paper is called Investing in Clinical Trial Compliance.

“The AAHC is actively pursing solutions to the complex cost issues through its Forum on Regulation,” said AAHC president and chief executive officer Steven Wartman, M.D.

Stephen DeSantis is the Senior Associate Editor at Thomson CenterWatch.

Underwriting Investigator Training in China

Posted by: Sara Gambrill
 
Eli Lilly and Novartis have made substantial investments in investigator training in China recently. Both companies are planning to make a big play there. Novartis has already said that it’s opening an R&D center in Shanghai this year. Lilly has not made its plans public.

With a population of 1.3 billion and a centralized healthcare system with access to millions of treatment-naïve patients per day, China has certainly attracted the interest of top 20 pharmaceutical companies. AstraZeneca has by far the largest presence in China. The country’s pharmaceutical market has been growing at a double-digit clip, dwarfing the growth seen in Western markets.

To further their goals, Lilly and Novartis have each donated tens of thousands of euros to the Vienna School of Clinical Research (VSCR) to fund the organization of investigator courses. VSCR seeks funding from industry and government to fulfill its mission of raising the level of professionalism in clinical research in Central and Eastern Europe and developing countries...

How Much is Enough? The High Cost of Source Document Review (SDR)

Posted by: Karen E. Woodin, PhD

Source document review, sometimes called source document verification, involves checking the data recorded in the case report forms against data found in available source documents, including the patient chart, laboratory reports and other supporting documents. (A source document is any document where the data are first recorded.)

The purpose of source documentation is twofold: first, to verify that the subjects exist and, second, to verify that data in the CRF are consistent with the information found in the source documents, which verifies the integrity of the data.

For example, one would expect to see basic demographic information in an office chart for a patient, including name, address, phone number, insurance information and a social security number.  The usual office chart will also contain lab reports or reports of other tests. This information is indicative that the person entered in the trial actually exists.

Cultivate Your Clinical Researchers, Pharma

Posted by: Sara Gambrill
 
Pharma companies know they have to reach out to new and inexperienced investigators to maintain capacity for growth in emerging regions. Investigator capacity is a major issue in these markets because they have experienced such significant growth in recent years. In the U.S., though, companies have taken more of a sink-or-swim approach when introducing physicians to clinical research, and they could be making a big mistake.

In the U.S. new sites are often given a chance to participate in clinical trials through competitive enrollment. If they meet patient numbers by a deadline, then they participate. If not, they waste a lot of time and energy for nothing, because often they don’t get a second shot at it.

MDS Pharma Services Top CRO in CenterWatch's 2006 European Site Survey

Posted by: CW Editorial

The Thomson CenterWatch 2006 European Investigative Site Survey marks the fifth time CenterWatch has surveyed investigative sites—those front-line researchers conducting clinical trials in Europe. MDS Pharma earned the top score for contract research organizations, improving from third place in the 2004 survey.

The factors rated most important by sites concerning CRO performance include being organized and prepared for a study, knowledge level of CRAs/monitors, quality of protocol design, timeliness of availability of the study drug, and simplicity of the case report form—critical aspects of study success.

-The complete article appears in CenterWatch Monthly's June 2006 issue and was written by Sara Gambrill, Senior Editor and Paul Dewberry, Research Analyst at Thomson Centerwatch.

-To read this article, or any other CenterWatch stories, visit our publications area.

Covance Boosts Phase I/IIa Capacity

Posted by: Steve Zisson

The search for top quality phase I sites just got even harder as Covance, a leader in the hot early clinical development arena, entered into a definitive agreement to acquire eight early phase clinical development sites from Radiant Research, a site management organization that owns 30 sites, for $65 million. Covance is paying about 2.5 times revenue for the eight sites, which generate $25 million in annual revenue. Seattle-based Radiant Research will continue to operate its phase II through IV sites,but employees associated with the eight phase I sites will become Covance employees. Covance, one of the top global contract research organizations (CROs), has more than 7,300 employees worldwide.

Steve Zisson, managing editor of Thomson CenterWatch.

We Found The Best Clinical Site Sponsor Companies

Posted by: Sara Gambrill and Steve Zisson

Contract and budget issues for sponsor sites are most likely to bog down clinical studies, but Wyeth is one of the best in the industry at managing the process.

So say researchers and administrators at 612 clinical sites we at Thomson CenterWatch surveyed recently. We asked these front-line professionals which sponsor companies work best with investigative sites and found that overall, Wyeth, Lilly and Genentech came out in a dead heat at the top of the rankings. Lilly is no surprise, consistently ranking among the top three in our annual survey, but Wyeth’s shot to second this year is a wake-up call for the rest of the industry – Wyeth finished dead last in our 2003 survey.