Congressional Sting Bites IRB - Who Benefits?

In March of this year, independent Coast IRB discovered what appeared to be a fraudulent clinical trial that had been submitted in 2008 for review by the IRB. According to Reuters, upon receipt of proof of the fraud, Coast ordered a halt to the clinical trial, alerted the appropriate state and federal authorities and instituted internal measures to prevent a recurrence. And that, Coast thought, was that.

Not so fast. Within days it was revealed that not only was Coast in fact the intended target of a fraud, but said fraud was perpetrated by the United States government in the form of the Government Accountability Office, whose website banner contains the words 'integrity' and 'reliability' to go along with 'accountability'. So instead of being the victim of a crime, Coast found itself in the dock before the U. S. House Subcommittee on Oversight and Investigations of the House Committee on Energy and Commerce on March 26th, answering charges that it had failed in its duty to protect human subjects from potential harm in clinical research.

As it turns out, the GAO created a fake protocol for a fake device, which they falsely claimed was FDA approved for sale, manufactured by a fake company in Virginia, developed a fake curriculum vitae for a fake investigator and submitted these documents to 3 different IRBs to induce them to perform reviews. The purpose of this elaborate sting was to "gather evidence to form the basis for arguments critical of the FDA and in favor of greater regulatory oversight" (Reuters, 11Mar09). Other components of the sting that did not involve Coast IRB were: establishing a fake IRB and advertising its services on the web, inducing a company to seek approval to add a site to an existing approved ongoing study (not to approve new research, which according to the regulations receives a different level of scrutiny than ongoing research); and submitting the fake name and qualifications of a fake IRB to the Dept. of Health and Human Services to receive an assurance approval number and be listed on HHS's directory of IRBs that review federally funded research.

Following review by 3 different IRBs of the fake device protocol and other documents, according to the GAO's report, 2 of the IRBs returned such extensive feedback that the GAO determined they 'did not have the technical expertise' to respond, and withdrew its applications. By contrast Coast IRB conditionally approved the protocol after a full board review, and contacted the 'sponsor' via the email address set up by GAO and sought at least two different interactions: one for proof of the medical qualifications of the proposed investigator, which the GAO provided by supplying a forged medical license number from the Commonwealth of Virginia. In another request Coast asked the 'sponsor' to modify the informed consent to make the language understandable at the 5th grade reading level. The GAO modified the informed consent as requested and resubmitted it, whereupon full board approval was granted.

I have requested of the GAO copies of the fake protocol and other submission documents for use in developing a teaching module on this episode, and so that we private citizens in the business can determine for ouselves whether the IRB met its obligations. I have yet to receive a reply.


After the truth of the scam came out at the Subcommittee hearing on March 26th, the FDA, in a response that can be filed under Closing the Barn Door After the Cows Have Gone, issued a warning letter to Coast IRB finding fault with them for not, among other things, determining that risks to subjects had been minimized, for not determining whether the FDA approval of the fake device was valid, failure to ensure that basic elements of informed consent were included in the consent form, and failure to determine whether the proposed research is acceptable under applicable regulations and law.

Nobody in Congress or the FDA seems to be the least bit concerned about the acceptability of perpretating a fraud upon a private organization without any prior suspicion of wrongdoing, of Kafka-esque harassment and eventual ruination of said company without due process, potentially in violation of several federal and state wire fraud and mail fraud laws, as well as state laws against false credentialing. According to Reuters, under the auspices of the Department of Jutice or pursuant to a court order, these practices would have been lawful. However this operation was performed at the behest of the legislative branch, not the judicial or executive.


On April 14th, Coast agreed with the FDA to submit itself to severe restrictions in its operations and to completely revamp its procedures to ensure full compliance with FDA regulations. However as of April 29th Coast has raised the white flag and will close its operations for good after transitioning all its active research projetcs to another IRB. The entire staff has been or will be laid off.


I am as concerned about patient safety as the next person and have a long track record of teaching students that no matter what their role in clinical research may be, however great or small, their first duty is to ensure patient safety above all else, including timelines, profit, and cost. So I question just who has benefitted by this targetting of a specific IRB - who had never received an FDA warning letter before - when it would have been so much simpler, and at the same time legal, to simply audit their files and determine through above-board means whether or not they were meeting their obligations to patients under the regulations. I do not see how patients are better protected when the government itself perpetrates fraud to create a new problem, when many profressionals believe the real problem lies in the fact that there are simply not enough good IRBs to cover all the research being conducted. Taking a potentially good IRB, at least once they had developed a procedure for identifying fraud, out of the equation does not seem to me to be the answer.

Risotto as a Metaphor for Life

I made my first risotto last night, pictured here, with green garlic and leek from the farm coop. The recipe is here. Making risotto is not quite as fearsome as one often hears, but you do have to commit to about 30 minutes of very frequent stirring once you start. And you do need to mise en place. Seriously. You don't have time to chop, wash or prepare anything once the first cup of broth goes in, or at least I didn't. I served the risotto with some fresh red snapper sauteed in a little butter, seasoned only with salt and pepper. Hard to go too far wrong. Everybody took seconds.

I had a conversation this week with someone who told me about Janus the god of beginnings and endings, whose face looks both forward and backward. She related this to people entering middle age and coming to realize that not only do people die, but I will too, and looking to make sense of what has come before to make the best of what comes next. That sounds like a good idea.


I got to thinking about the nature of motivations. If I want to make a big change what is my motivation? To explore new challenges? To have more control of my future? To engage my brain a little more? Does destiny have a role? Or is it just about luck, and are they actually different?

I know I am supposed to blog about my visit in Germany with family. There is so much to tell there, it is hard to get started. Soon, soon...

Life as a locavore

Here is the bag of vegetables from my farm coop last week: beets, leeks, carrots, artichokes, chard, fava beans, broccoli, apples and green garlic. This was the third week of the season, our first in a farm coop and I am starting to get the rhythm of it: pick up a huge bag of produce on Thursday after work, cook like a fiend for the next several days trying to use as many ingredients as possible each night, start casting about for unsuspecting neighbors to palm off any remaining veggies that I either couldn't figure out what to do with or we didn't like, clean out the fridge by Thursday and start the process all over again. One change is already in place: we are eating out a lot less. Which is kind of a bummer because I liked going to the local Indian restaurant on Thursday night after everything was done - Thursday is kind of like a Friday for me because I work from home on Fridays - but now I think about all this minutes-from-the-ground produce aging in my refrigerator, and so I cook instead. Lucky for me, the Minimalist (Mark Bittman of the New York Times) has been writing about the same foods so I've had a new source of recipes. Last night I made his carrot, spinach and rice stew, adding green garlic and cup-up chicken thighs, and heated up some roti for bread - absolutely delicious.

A couple of weeks ago Passover sort of snuck up on us, like everything seems to these days. All of a sudden I realized we hadn't planned anything, so I hastily prepared the ceremonial foods (from my farm coop bag, natch) and invited one of Rob's constantly hungry riding partners and managed with some help from Sean to get the entire meal on the table in about 2 hours - blazing speed for a Seder. I used Sydnee's homemade Seder plate, here.

Closing the Loop

The picture is of a colleague named Paul Loveday. I met Paul in 2007 at a conference in San Francisco. He was the founder and CEO of ClinStar, a CRO in Russia. At 6'10" Paul, a former NBA basketball player, was hard to miss in any room. During a coffee break on the first day of the conference, he loped up to where I was sitting, dropped to one knee (he was still tall even when kneeling) and said "Should I know you?"

There was no earthly reason why he should have. I said, "Do you mean in the metaphysical sense?", he laughed and from there an easy acquaintanceship was struck. I believe I only saw Paul 3 times during the 17 months that I knew him, yet I felt as though I knew him quite well - well enough to ask him to guest lecture twice to my UC class on emerging markets, by phone, all the way from Moscow at 6 AM his time, for 90 minutes at a stretch. Paul had a presence that made whoever he was speaking to feel as though they were the only person in the room. I would not be surprised if there were literally hundreds of people who only met him 3 times, and yet felt they knew him and he them.

The last time I saw Paul was in July of 2008. I was about to speak at a conference on emerging markets in Washington DC - the same conference where I had met Paul the year before - and he said he was planning to heckle me during my talk. I said "Bring it, Paul, bring the heat" and he laughed. His colleague had invited me to go with them for dinner the previous evening but I had declined in favor of previous plans.

The last time I heard Paul's voice was on November 10th, 2008. He called into my class on emerging markets from his office in Moscow and held forth on the benefits and challenges of doing clinical trials in Russia and Ukraine - preferably using his CRO - and somehow managed to make each student in the class feel as though he was standing in the room talking instead of thousands of miles away over a phone line.

In January as I was planning speakers for the spring offering of the emerging markets course and wondering if asking Paul to lecture again was going to the well too many times, I received an email out of the blue from his business development colleague Erin, with whom I had also become friendly. She wrote me that Paul had died suddenly in St Petersburg, 17 days after I last heard his voice.

The loop finally closed when I saw Erin at a two day meeting in San Francisco a couple of weeks ago. Together with the new president of ClinStar, Erin and I mourned. She told me that during the time she worked with Paul, she had often spent long stretches of time with him doing business development, broken by long stretches of time that she did not see him at all when he was in Russia running the business. She said she hadn't really accepted that he is gone, she just thought of him as still in Russia. She kept referring to him in the present tense; we both did. We talked about how their business would go on. We talked about dreading the next summer emerging markets conference without Paul. Erin told me that her sense was that Paul was getting ready to take on his next great challenge - she wasn't sure what it was but now we will never know.

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While I was still at this same meeting, I got a call from my mother with the news that my father has severe aortic stenosis with a not very good prognosis due to his age and other factors. He is not a good candidate for surgical valve replacement, which gives him a life expectancy of months, not years. He may be a candidate for a clinical trial, in which case the way I have spent my adult life earning a living may actually let me help my parents out by cutting through some of the barriers. My mother has a vague mistrust of experimental therapy (despite my careful explanations - what is that saying about a prophet not being welcome in her own hometown?); my father is all in for any reasonable chance to go on living as long as he can. I am walking a fine line of gathering information and pushing to keep the doors open and trying to keep the ball rolling for the trial which is very complicated, while still respecting my parents' autonomy. I take a deep breath whenever my phone rings and I see my mother's caller ID, wondering which call will be the one I'm dreading.

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I met with an old acquaintance this week whom I had not seen for several years after a falling out. It was surprisingly easy to make the small talk, but difficult to broach the subject of the disagreement. Once I had finally said my piece, she said "Fair enough. Water under the bridge?"

That was all. And it occurs to me that yes, the water is long gone under the bridge, but the bridge is no longer there either.

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Finally I am off to Germany next week to close another loop long left open. No doubt that trip will generate future blogging. Another day.

Focuses for the Upcoming Term

This tide marsh is located behind the building I where I work Monday through Thursday, on the east side of the San Francisco bay. It is close enough to walk to, and it has long flat dirt paths to run on when I feel energetic. On a clear day, such as we had this week, you can identify individual buildings in the downtown San Francisco skyline. Most days there is a haze on the water that precludes even seeing the mountains of the peninsula on the other side. I like to go out there during the day to clear my head or to think. Sometimes if I don't have early morning calls I stop by the marsh before heading into the office to watch the great white herons, snowy egrets, mallard ducks and other shorebirds make their living. I find the movement of the tides calming. The water of the bay has a different personality every day; sometimes calm, flat and glassy, sometimes grey and choppy. But the water in the marsh, seen here at high tide, is always smooth and tranquil.

The focus of this week has been building my network of experts in the field of clinical trials in emerging markets. I'm starting to do some research into the area of informed consent in emerging markets: what does signing a form mean to the patient, why are we shoving 15+ page consents down people's throats, and why do the ethics committees let us? I will be contacting my Indian, Eastern European and other connections in the developing world (although they don't know it yet) in the coming weeks to get their perspectives for the next iteration of the emerging markets course, to be offered in the spring term.

The winter term at UC Santa Cruz starts for me next week. It's been about an 8 week break since the fall term ended. Good Clinical Practices, my flagship class, begins Wednesday evening Jan 21 from 6-9pm, and runs for 10 weeks. I've improved (I hope) the curriculum for this term, updating some older information and including references to recent events in the NY Times, NPR, and other sources.

Looking for a Silver Lining

My notes for this week's entry carried a theme of relationship. As I get older I've learned to recognize that companies don't do business with each other - people and relationships do. Sometimes when I go back to a company that I enjoyed working with before, I find that the next experience can be markedly different - and sometimes poorer - and it is all because of the people. More and more in recent years I've invested in relationships with the people with whom I do business, relationships that in my younger days I would have taken for granted, because I find it is those relationships that not only make the job more enjoyable, but also get you through the tough times. I have been in the clinical research business a long time - there is not much exciting about doing new studies anymore. On the other hand, building relationships and networks with great people makes doing the same job more interesting.

None of us is irreplaceable; whenever someone leaves, it almost always creates an opportunity for someone else to grow into their own potential. And I have always believed that people should do what they need to do and are never indebted to their employer or me or anyone else. Still it is hard to say goodbye sometimes.

Looking to 2009

The 2008 holidays are winding to a close and I've been thinking about the coming year for a few weeks now. Here are some lessons I take into 2009:

Lesson #1: Contracts come and go; relationships are as permanent as you make them. Any successes in my working life this year have been achieved entirely through investing in relationships, in some cases for years. This is a source of joy for me, as I am reminded this year more than many that when I am in my rocking chair looking back over my life, it is the people I will remember, not the goals and milestones hit or missed. Banking on my credibility with staff, management, partners and others is scary but ultimately very rewarding.

Lesson #2: Surround yourself with smart people and then listen to them. Kind of a corollary to lesson 1, could be restated as 'know your limitations and fill them'. 2009 will see me focusing on networking far more than previous years.

Lesson #3: The future is a little farther away than it was a year ago. For the last 10 years I had planned to retire from full time clinical research by my mid 50's, now just about 3 years away. The global recession thinks otherwise, and I am gradually accepting the fact that I will be working longer. On the plus side, thanks largely to heeding some very good advice (see lesson 2 above), we are down slightly less than the market at large, above water on our home and carrying no consumer debt, and the college expenses will probably wind down by 2012 or thereabouts. In my worklife I am focusing on developing greater expertise and networks within the field of clinical research in emerging markets. I shared some of that expertise at a couple of conferences in 2008 and hope to develop more such opportunities in the coming year.

Focuses for 2009:

1. build credibility
2. invest in relationships
   
3. simplify wherever possible - the common sense approach is usually the right one
4. rebuild capital through wise investments and sound spending
   

2009 looks to be a challenging year in all arenas, but we will get through it. See you in the trenches.