FDA Gets New Authority Over Clinical Trial Reporting

Here is an interesting development in the ongoing controversy over reporting clinical trial data in all its glory to the federal government. The US Department of Health & Human Services has transferred authority to the FDA to oversee information that is filed with ClinicalTrials.gov - the clinical trial registry data bank - and seek out those who fail to file, or file misleading or false data, according to a statement in the Federal Register ( see here).

Of course, the FDA reports to the HHS, but the move is likely to be more than symbolic, given the scandals that have ensued in recent years over a failure to provide complete trial data. Examples include the Avandia diabetes pill sold by GlaxoSmithKline, which recently paid a $3 billion settlement, partly for failing to report safety data (read this). And evidence that Merck hid risks associated with its Vioxx painkiller continues to emerge (look here).

The notice says that the FDA now has a green light to pursue "...any clinical trial information (that) was not submitted as required under (federal law) or was submitted but is false or misleading in any particular, and to notify the responsible party and give such party an opportunity to remedy non-compliance by submitting required revised clinical trial information not later than 30 days after such notification." The transfer of authority was first reported by Regulatory Focus.

In recent years, studies have shown that some clinical trial data often goes unreported. A 2009 analysis published in PLoS Medicine found that data mandated for reporting to ClinicalTrials.gov was nearly 100 percent, but reporting of optional data and publication rates were low. For instance, 53 percent reported trial end dates, 66 percent reported primary outcomes and 87 percent reported trial start dates.

Among a subsample of trials examined, those primarily sponsored by industry, or 40 percent, were less likely to be published when compared with trials not sponsored by industry or government sponsored trials, or 56 percent, but there was no significant difference when compared with government-sponsored trials. "Without greater attention to reporting of all data elements, the potential for ClinicalTrials.gov to address selective publication of clinical trials will be limited," the authors wrote (read here).

Earlier this year, a series of papers in BMJ found a host of problems with reported trial data. One paper examined unpublished evidence of existing meta-analyses of nine drugs approved by the FDA in 2001 and 2002, but found identical estimates of drug efficacy in only three of 41 cases, or 7 percent. Estimates of efficacy were split evenly split in the remaining cases when unpublished FDA trial data was examined.

Another example: The Food and Drug Administration Amendments Act (FDAAA) requires mandatory reporting of summary clinical trial results within one year of completion on ClinicalTrials.gov. But one BMJ paper found that only 22 percent adhered to the mandate. Generally, later phase trials and industry-funded trials were more likely to report results. Another recent study found even lower compliance.

Still another paper looked at trials that were funded by the National Institutes of Health between 2005 and 2008, and found that only 46 percent were published in a peer reviewed biomedical journal indexed by Medline within 30 months of trial completion. And three years later, one third still remained unpublished.

In a widely quoted accompanying editorial, BMJ wrote that “there is an ‘Alice in Wonderland’ feel to these investigators’ efforts – acting on the public’s behalf, searching over hill and dale and among the paperwork of regulatory bodies and drug companies to put together pieces of data that should have been freely available in the first place" (here is the back story with links to the various papers).

21 Comments

Sep 25, 2012 - 12:19pm
FDA has all the study reports. Let them fill in the blanks themselves in between their time spent on insider trading.
Sep 25, 2012 - 12:37pm
@oii - agreed, such a shell game, like watching the hustler on the street corner..."under which cup is the data"...
Sep 25, 2012 - 5:34pm
dz - your comments have almost ruined my day...here I was envisioning Lilly execs going to prison for what they omitted from the Zyprexa clinical trail data - 12 or 13 suicides and well, you know about the weight gain. Are we sure the FDA actually had this data?
Sep 25, 2012 - 6:45pm
Senator Grassley introduced a bill a few years ago, with a Democratic co-sponsor, that would have required that all clinical trial data would be released into the public domain. Of course it died in the HELP Committee. Until this information is public knowledge, or required as the ticket to admission to formularies (and then accessible to the public), tens of thousands of people a year will continue to die from the lethal side effects of prescription drugs. Or grow breasts, get diabetes, etc.

What corrosion of the soul must result from working for pharma. Or, for that matter, the FDA.

Sep 25, 2012 - 7:51pm
My soul ain't been corroded. On the contrary, per the Chambers Brothers:

"Now the time has come There's no place to run I might get burned up by the sun But I had my fun I've been loved and put aside I've been crushed by the tumbling tide AND MY SOUL HAS BEEN PSYCHEDELICIZED

Better believe it bro.

More lyrics: http://www.lyricsmode.com/lyrics/c/chambers_brothers/#share

Sep 25, 2012 - 8:49pm
Would Grassley have the brass to introduce the same bill (let alone work with a Dem co-sponsor) today?

I doubt it, but I hope someone will prove me wrong.

FDA is the right place to study report.The post with Example gives me clear knowledge about FDA New authority of data. Thanks for the useful info.
Sep 26, 2012 - 9:28am
My soul is just fine Tim.

During the years I've been in the industry, the annual number of deaths from AIDS in the US has dropped from 55,000 (and growing at a 25% rate) to around 15,000. The treatment of rheumatoid arthritis has been turned on its head. And the number of deaths from CV disease has fallen by about 100K per year in spite of increasing prevalence of obesity.

How's your soul these days?

Sep 26, 2012 - 1:17pm
@Alice - ask the admin - she hit the "send" button and has an e-response from FDA that it was "received". Not her "job" to tell you what all that stuff she just sent means.

Probably most of the retired folks who have the photographs of them and their team standing in front of the back of the fully-loaded truck with paper data headed for the FDA are in "good" nursing homes with the clock ticking out for them because the profit margin is impacted if they stay alive any longer - "med change" a-coming...bye-bye...so you better hurry and ask them if everyone in the photo KNEW what was on that paper going to FDA

So yes, the data is at the FDA and as I said before there are fewer people - both at FDA and at the "sponsor" company - who hold the responsibility for knowing what was in the data.

Hence the street corner shell game going on....again.

@John - indeed, the effort of thousands of people over decades has been shoveled to the top where "god" can say, "I built that and it is good". Not the issue, though. The issue is that it won't trickle back down to Main Street. Darth Vadar lives on and on with tax payer $$ funded top shelf "knowledge", the iconic astronaut who inspired the hoi-poloi was buried with honors. Some hearts take a licking and keep on ticking - with or without a "soul".

Sep 26, 2012 - 1:47pm
Ditto, John. If you're like me you may care less about what happens to our souls than the millions of souls our industry has saved, as you so nicely said.

"The evil that men do lives after them, The good is oft interred with their bones.."

Tim et al, you can diss on our business all you want after I'm gone. I don't give a sh**t about people like you who lack the historical perspective on our industry that John has presented so very well.

Sep 26, 2012 - 6:25pm
http://www.drugwarfacts.org/cms/Causes_of_Death

dueling data to infinity and beyond...so sick of the slickness of cut and pasting...sigh.

BTW, the growth of new HIV infections worldwide is going to rapidly dwarf the gains.

"The treatment of rheumatoid arthritis has been turned on its head." - have no clue what the dude is referring to here...

"And the number of deaths from CV disease has fallen by about 100K per year in spite of increasing prevalence of obesity." - which year was baseline and what is today's trend?

Sep 26, 2012 - 8:27pm
Tim, with your focus on the side effects you forget the WANTED effects of the drugs. If people didn't take the anti-psychotics that caused weight gain and diabetes, would there have been more psychotic episodes, more manic episodes, maybe more suicides? Many people who take Zyprexa love the way they feel on it contrary to people who took Haldol or thorazine and felt like zombies and developed Parkinsonian like symptoms so they stopped taking it.

As a wise person once said about this industry, all drugs have effects, both wanted and unwanted. The unwanted effects are called side effects. What the FDA does is an evaluation of the wanted versus unwanted effects.

I do agree that people should know about both the wanted and unwanted effects, but research has shown that many people don't know how to think through probabilities very well. It's a special form of math literacy that the US doesn't do very well. I think a major effort needs to be put into helping people think through the risks and benefits for themselves. Ensuring that the information is up on clinicaltrials.gov is one important, crucial step but it isn't enough.

Sep 26, 2012 - 11:01pm
Alice:

"12 or 13 suicides and well, you know about the weight gain. Are we sure the FDA actually had this data?"

Yes, you can read it in the FDA's approval documents here. http://www.accessdata.fda.gov/drugsatfda_docs/nda/96/020592_Original_Approval_Pkg%20.pdf

And I'll repeat yet one more time that the "12 or 13 suicides" that were seen in the Zyprexa clinical trials were matched almost exactly in rate (0.38%) to those seen in the placebo treated arms (0.44%). But of course to those with an axe to grind, the "12 or 13 suicides on Zyprexa" can be quoted endlessly with the implication that the drug and not the underlying disease was responsible. And they can be forever presented as part of a coverup, even though they are discussed in the FDA approval docs readily available on the internet.

Sep 27, 2012 - 11:04am
@MDivStudent - it would be so refreshing to see a heavy thinker assume people aren't stupid for a change.

But I'm all for teaching "probability". Start with deaths due to car accidents and tie it all together. Drunks and the drugged out always seem to want to assess whether they're still "okay" by seeing how well they can drive...

Sep 27, 2012 - 5:40pm
I'm sorry, I just don't understand. The FDA is recently outed as being corrupt and threatening to its scientists. And yet here we are giving them more responsibility. Authority even! The wormhole of "lost information" amongst pharma trial data is epidemic. How exactly does this help the situation. The government is in the pocket of pharma and pharma sucks the teet of government lobbyists. This is a proven fact. "According to a new report from Brandeis University, prescription painkillers — opioid or narcotic pain relievers like Vicodin (hydrocodone), OxyContin (oxycodone), Opana (oxymorphone), and methadone — are now responsible for more fatal overdoses in the U.S. than heroin and cocaine combined." Statistic: according the Centers for Disease Control and Prevention, enough prescription painkillers were prescribed in 2010 to medicate every American adult around-the-clock for a month.  Doctors recieve incentives from Pharma- Trial scientists are stifled and harassed- and now the FDA is responsible for it all. Other than Original Industry Egomaniac- can someone explain the benefit of this redundant shell game?
Sep 27, 2012 - 6:47pm
Despite your derogatory comment I will explain. A slip of the tongue by an FDA reviewing official into an open microphone a while back went as follows: "We're not here to review drugs, we're here to approve drugs".

God bless the PDUFA fees. They are the bread and butter of the FDA and they damn well know it. What's that song, "I've got you under my thumb"...

@ John;

Why is it the medical side of the argument has answers for Everything except How their narcissistic little researching, social engineering Treasury Raids are going to be Paid For?

"During the years I’ve been in the industry, the annual number of deaths from AIDS in the US has dropped from 55,000 (and growing at a 25% rate) to around 15,000."

Adult age 15-49 HIV/AIDS prevalence by country: http://www.globalhealthfacts.org/data/topic/map.aspx?ind=3

America 2009: 0.6%

Death from HIV/AIDS has been minimized

To Bug Chasers HIV isn't a Ruthless Killer, It's A Gift http://newsrescue.com/in-search-of-death-to-bug-chasers-hiv-isnt-a-ruthless-killer-its-a-gift/#axzz27iDH8K9h

"For Carlos, bug chasing is mostly about the excitement of doing something that everyone else sees as crazy and wrong. Keeping this part of his life secret is part of the turn-on for Carlos, which is not his real name. That forbidden aspect makes HIV infection incredibly exciting for him, so much so that he now seeks out sex exclusively with HIV-positive men.

And the COST to Everyone Else of keeping Carlos alive IS? http://www.npr.org/blogs/health/2012/07/27/157499134/cost-of-treatment-still-a-challenge-for-hiv-patients-in-u-s

"With the life expectancy for HIV patients increasing, the lifetime cost of treatment in today's terms is estimated at more than half-million dollars."

0.6% of 2009 Americans are infected. That's 1.8 Million people @ more than $500,000.00 each.

That's $900 Billion Dollars to keep Bug Chasers alive, actively Spreading the Disease because they enjoy it.

But at least Medicine can "Feel Good" about itself by Behaviorally Engineering the 'incredibly exciting, forbidden aspect' that Carlos so enjoys.

Our great great grandchildren are $16 Trillion in debt, and I've No Doubt that a great many of Carlos fellow Bug Chasers are Also good for Another lifetime $Million in SSDI payments thanks to Another crop of parasitic Behavioral Engineers.

But at Least, Medicine, and Carlos can 'Feel all warm and cuddly about themselves' because, They are All 'Incredibly Excited'.

@ John;

Sorry, Here's that Other SSDI $1 Million Apiece tossed down a rat hole by our beloved Dr Feel Goods ministering so generously to Carlos and his Incredibly Exciting adventures, ..... on money our great great grandchildren Don't Have.

http://psychroaches.blogspot.com/2012/02/psychiatrys-raid-on-americas-ssi-ssdi.html

Sep 27, 2012 - 7:32pm
http://en.wikipedia.org/wiki/Opium_production_in_Afghanistan

He with the gold rules. So as USA continues to shed Middle Class jobs supposedly due to "technology" (really? a toy factory in Texas could not compete according to Mitt et al) and to cheap global labor, the nouveau riche are rolling in "equity" from agriculture, cell phones, and pain. No pain, no gain.

FDA is maintaining our Drug Lords' position in the world. So what's the problem, pops?

cut and pasted:

"...Impacts of opium production within Afghan villages:

Aside from the obvious threat of addiction, opium production is changing the dynamic of many Afghan villages. Wealth distribution, for example, has changed significantly as the opium economy has created a “new rich” in which young men have control. This new found wealth for the young men of Afghanistan is troubling to many of the village leaders as before they were revered for their wisdom, and now are given little if any respect. It has also been noted that relationships among fathers and sons, neighbours, and family in general, are drastically changing as leadership roles in the economy continue to shift.[41] As the young men have increased contact with the outer world, they have become aware of different methods of performing traditional tasks, which have created tensions between the young men and the white beards. Also, there has been a shift from the level of co-operation, trust, and reciprocity within villages to a move of self interest, all of which have been adversely affected by the war.[41]"

Wait until Ayn Rand is translated to Pashtun. And they got nukes next door...

Have a wonderful evening, y'all! Luv ya!

Sep 28, 2012 - 4:27am
You have spent the research money. Now justify it by properly reporting the results and what you have learned, positive or otherwise, and allow people to judge whether or not you have done good science and hence the value of the results. Too simple?
@ Alice & Tim;

http://psychrights.org/States/Alaska/CaseOne/30-Day/ExhibitD-Olanzapine.htm

You might like to examine Dr. Grace Jackson's analysis of the Zyprexa Trials the FDA used to release it on the world.