OT:New Clinical Trial Mandate Poses Concerns for Drug Firms

[Guest guest]

New Clinical Trial Mandate Poses Concerns for Drug Firms

BioWorld Online - Atlanta,GA*

By Donna Young

BioWorld Today Washington Editor

http://www.bioworld.com/servlet/com.accumedia.web.Dispatcher?

next=bioWorldHeadlines_article & forceid=47152

Reports that clinical trial data were being suppressed led Congress

last fall to pass legislation requiring drugmakers to submit study

information, other than Phase I, to a publicly accessible registry

and results database.

The law, enacted Sept. 27 as part of the FDA Amendments Act (FDAAA)

of 2007, is intended to make clinical trial operations and results

more visible to the public.

However, said analyst , of W. Baird & Co.,

disclosures of a firm's clinical trial data, including the details

about a study's design, may put manufacturers at risk of losing

their competitive edge. Clinical trial results, he added, could

contain information about a signal for a mechanism for which a

company may not want its competitors to be aware.

Biotech and other drugmakers also are voicing concerns that the

disclosure requirement may accelerate the move toward overseas

trials, and could make companies more reluctant about conducting

trials that provide more clarity into the particulars of how a drug

works.

Drugmakers also are worried that putting clinical trial data in the

hands of the public could lead to study results being misinterpreted

or misconstrued to support a political agenda.

The measure, known as FDAAA 801, expands the types of clinical

trials that must be registered with the National Institutes of

Health (NIH) online database, known as ClinicalTrials.gov, increases

the number of data elements that must be submitted and also requires

submission of certain results data.

The government can impose penalties on medical product manufacturers

that fail to comply with the law, such as civil monetary fines and

withholding or withdrawing grants for federally funded trials.

Some of the reporting deadlines for the registry took effect this

past December. Manufacturers, or their designated principal

investigator, must register clinical trials of drugs and biologics

subject to FDA regulation within 21 days after the first patient is

enrolled.

Submissions must include trial descriptions, recruitment, location,

primary and secondary outcome measures, start date, target number of

subjects, and contact and administrative information.

NIH and the FDA are working together to create the results database,

which was mandated to be in place by September of this year.

Results of clinical trials for approved drugs must be made publicly

available within 12 months of a study's completion. Results of

studies conducted prior to the FDA's approval of a product, other

than Phase I studies, are required to be posted on

ClinicalTrials.gov within 30 days of the approval, said NIH's

Deborah Zarin, who recently co-authored an article about FDAAA 801

in the journal Science.

" If the intervention is never approved, the trial results do not

need to be posted at this time, " she said in an email response to

questions.

However, the NIH and the FDA are still working out the rules for the

law's requirements. While language in one area of the legislation

makes it somewhat clear that only results of approved drugs must be

reported, FDA officials said other language in the bill leaves open

the question about whether study results of new uses for approved

should be reported.

The legislation also requires regulators to address whether to

include reporting requirements for unapproved drugs in their

rulemaking.

Regulators have three years from the law's enactment to finalize the

rules and fully implement the clinical trial reporting requirements.

Officials noted that the NIH must convene a public hearing about the

results database mandate by March 27, 2009. " It's a work in

progress, " an FDA official said.

Pushing Trials Overseas?

The new mandate, said, may drive a growing trend of firms

conducting their clinical trials overseas, such as in Eastern

Europe, rather than in the U.S. and seeking approval of their

products in foreign nations first.

While forcing companies to make their data public may be amplifying

the desire to move clinical trials outside the U.S., argued

Rothman, vice president of clinical development for North Brunswick,

N.J.-based Advaxis Inc., firms are going overseas more because of

the thorny regulatory obstacles they face here.

Because of the rising costs and increasing regulatory burdens of

conducting studies in the U.S., Rothman maintained, it often makes

more sense and is more financially efficient for biotech and

pharmaceutical firms to generate early-stage data in foreign

nations.

The recent firestorm about suppressed study data, which led to the

passage of FDAAA 801, has made drug developers reluctant now more

than ever to conduct trials simply to answer a scientific question,

which may be unrelated to a new drug application, said Tom Lang,

chief drug development officer of Las Vegas-based Samaritan

Pharmaceuticals Inc.

" Sometimes studies are done for a number of reasons, " such as to

compare dosages, he noted.

" Sometimes companies will do studies around their core studies to be

able to get a better feel for where the drug may or may not be used

in other indications, " Lang explained. " And those studies will have

to be published, and they may look contradictory or they may be

something that you'll be explaining for a very long time, " he added.

A Fear of Misinterpretation

Much of the concern about putting study details in the public

domain, Lang noted, revolves around the fear that those results will

be misinterpreted.

" You could kill a very good drug just by having misinformation, " he

said. Manufacturers, Lang contended, are not going to put

their " billion dollar drug " at risk to answer a research question

for which the study results could be misconstrued.

With FDAAA 801 firmly in place, Lang said, he expects drug

developers to be more careful about the types of studies they

conduct " because they are not going to want to have misinformation

out there that's going to maybe destroy a good drug that has a lot

of potential to help people. "

The risk of being misunderstood, Rothman contended, is significantly

elevated " now that medicine has become so politicized. "

" There are people who are not necessarily interested in the truth

but interested in supporting their own political position, " he

asserted. " We are in a period of time where politics is intruding

into science in ways that complicate the science and make it a lot

more expensive, " Rothman added.

However, he noted, there always has been some potential for abuse by

those who seek to bias the facts about clinical trials.

, CEO of Advaxis Inc., which is investigating the

ability of the microbe listeria to activate the immune system to

treat cancer, said companies already are guarded about conducting

trials for which the outcome is unknown.

" The rule in law for centuries has been when in court never ask a

witness a question for which you don't already know the answer, "

said. " Unfortunately, for clinical trials, you don't have the

luxury of doing that. You just don't know what answer you're going

to get, " he added.

The industry is increasingly trying to move towards evidence-based

medicine and the ability to determine in advance what drug is best

for the patient, noted.

However, he said, in the current environment of consumer- and

professional-oriented marketing, the desire by drug developers to

conduct comparative trials is impeded by the perceived risk of

results being misconstrued.

But, added, that risk is one the drug industry already was

struggling with before the new reporting requirements were put in

place.

Data Are Evidence of Productivity

Small biotechs and drug firms may benefit from having their study

data publicly available because it is evidence of a company's

productivity, Lang said. Even without the mandate, he said, it was

getting more and more difficult for companies, large and small, to

keep their data hidden from view because of investors' interests and

need to know.

agreed, adding that " anytime you raise funds, you absolutely

must do a complete disclosure. "

The investor market, he said, is focused very closely on how a

company's pipeline progresses.

" I don't believe we have the option to sit on any clinical results,

even if we wanted to, " said.

Published March 24, 2008