Electronic Medical Records & Clinical Trials

March 30, 2009

An important centerpiece of President Obama’s stimulus package is to encourage electronic medical records (EMRs). Last September I made my own contribution regarding EMRs in an article for Applied Clinical Trials (“The Ins and Outs of EMRs.” I am posting it on the right under interesting articles. I am also posting a recent NPR article, “Electronic Medical Records, a Charged Debate.”

For those of us who monitor and audit EMRs for clinical trials this is a tricky issue. NPR points out it is a tricky issue for a number of other reasons. As always, I welcome your comments.

Update: See Update on EMRs under Interesting Articles for an update I wrote for Applied Clinical Trials online edition.


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The word on FDA from North Carolina

March 22, 2009

“FDA Ignores Whistleblower” the headline screamed at me as I rushed through the Raleigh Durham International Airport. However when I arrived home in Washington state my local paper hadn’t carried a word about it. Neither had the NY Times. Fair enough, the article from the News Observer, posted under interesting articles on the right, was about the safety of syringes manufactured in North Carolina. But the manufacturing problems- and FDA’s failure to address them, impact the health and safety of us all. Over 100 people became sick from bacteria laden syringes and five people died. North Carolina reader’s have commented on the article and, although most are expressions at rage at FDA, there is one thoughtful comment on the need for better quality control and quality assurance systems and how they make for good business practice.

It will be interesting to see if the new team of Hamburg and Sharfstein can solve some of the systemic problems with FDA inspections. From my review of the article it seems that at least one inspector was attempting to do a good job although she didn’t get to the whistleblower’s issue of the syringe clean room where the bacteria contaminated the syringes. It seems like a management problem to me.

You can read additional posts on FDA Commentaries here:



Acting FDA Commissioner issues a “privacy memo”

March 20, 2009

Acting FDA Commissioner Frank Torti has issued a memo to FDA staff with strong words on maintaining confidentiality of FDA documents, including e-mails and memorandums. It’s causing something of a stir although I personally think that all of the restricted areas that Torti mentions should indeed be kept confidential. However, it is very interesting that an Acting Commissioner would issue such a stern memo to agency staff. Read for yourself. The memo is listed under Interesting Articles to the right. Also under Interesting Articles is a blog entry from the In Vivo Blog. Interesting stuff.

DSI Hits Hard on Human Subject Protection

March 15, 2009

The Division of Scientific Investigations (DSI) in FDA’s Center for Drug Evaluation and Research used to be something of a joke when it came to enforcement. In fact, in Fiscal Years 2005 and 2006 they failed to issue a single Warning Letter. Not one. Well, things have changed. In the article “Bimo Warning Letters for 2008” found on the page at the Blog Top I mention that DSI has started to issue Warning Letters for clinical trials. Now, DSI has issued three Warning Letters dated 2-3 March for some very serious violations of regulations protecting the rights, safety and welfare of participants in clinical trials. Although I have questioned some of DSI’s judgement in the past few years, all three are richly deserved. They are all sent to clinical investigators (the medical doctors conducting the research).

In the first Warning Letter the clinical investigator had three lapses in approval by an institutional review board (IRB), the longest lapse in approval was for five months. IRBs are the independent ethics committees that oversee clinical trials. Not having independent review of research is a very big no-no. The Warning Letter included a citation for consenting a participant, also referred to as a “subject,” first with an English language consent form and then later re-consenting the participant with a Spanish language informed consent form. This indicates that the participant was probably only fluent in Spanish. An informed consent form must be in the language used to provide informed consent to the participant. This is another essential right of people participating in clinical trials, the right to informed consent and to not participate if they so choose.

The second Warning Letter involved pediatric trials for Zemuron, a Schering Plough drug used in relaxing muscles during surgery and mechanical breathing. This time FDA cited the clinical investigator for failing to adequately supervise “individuals to whom you delegated study tasks…resulted in inadequate informed consent documentation…failed to obtain legally effective informed consent.” There were numerous problems at this study site that involved false signatures from the study coordinator (the clinical investigator’s primary assistant) and consent forms dated by study personnel instead of the study participant.

The third Warning Letter documented that all 18 participants who enrolled in the study “received study dug prior to your review and assessment of baseline laboratory results…were infused intravenously…” The clinical investigator (again, the medical doctor conducting the study) didn’t review the laboratory results from three to 20 days after infusing the investigational drug product. This is a big deal for three important reasons.

First, you never start a clinical trial before all requirements are met. Clinical trials are experiments, not the practice of medicine. Second, the clinical investigator was dealing with very ill patients. They were having IV drug infusions. He should have reviewed their lab results regardless if they were participating in a clinical trial.

Finally, and this is the first of two points I am trying to make in this post, the clinical investigator failed to establish a clinical baseline for the participants. This is an important concept for those of us who are involved in the conduct of clinical trials as our profession. There needs to be a clearly established clinical baseline, the medical condition of the participant when the study begins. And you really want to DOCUMENT the clinical baseline. This is important to determine if the drug is safe and effective.

The second point I would like to make is that it is very disturbing that clinical research in the United States is being conducted with these ethical violations. If you have read this far you probably know that there are problems with the conduct of clinical trials, with drug safety, and the entire new drug approval process. We know that FDA needs to improve its performance if it is to adequately protect the health of the American people. The question is what needs to be done.

I would like to suggest that putting more requirements on institutional review boards (IRBs), the ethical committees that oversee research, is not the way to go. Instead, I believe that we need to modernize the clinical trial regulations that came into being in the 1970s. In particular, I believe that we should make the Consolidated Good Clinical Practice Guidelines, ICH E6, into regulations, instead of a guidance document that cannot be legally enforced. This document was written with extensive input from FDA. It is the law in Europe, Canada, Japan, Australia, and many other countries. Our regulations are outdated and don’t give researchers the necessary oversight to ensure ethical clinical trials.

Unfortunately, over the years IRBs have been criticized for not providing the necessary oversight. This isn’t the responsibility of the IRBs, it is the responsibility of FDA. FDA needs to perform more effective inspections of clinical investigators and IRBs. However, FDA does not have the resources, and until now DSI did not have the will, to enforce protections for participants in clinical trials.

Currently IRBs are being investigated by a Congressional subcommittee chaired by Representative Bart Stupak. The investigation should be discussed at a hearing later this month. I think that they may be looking in the wrong place. There are two sets of regulations for IRBs in the U.S. which is confusing to many (FDA regulations and Department of Health and Human Services, 45 CFR 46). The regulations are enforced by two different federal agencies with different approaches. Out of date, conflicting regulations just don’t help very much.

In fact, the FDA “Compliance Program” for IRBs hasn’t been updated since 1994. It was due to be updated in 1997, 12 years ago. The compliance program is the blueprint for FDA field investigators to conduct an inspection. FDA has outdated regulations, field operations, and funding.

I am also posting E6, the combined guidance for Good Clinical Practice (GCP), and other ICH documents. Finally, I am posting the link for the outdated compliance program for the inspection of IRBs. It is high time that this document was updated. As always, I welcome your comments.

Drug Safety? Good news/bad news

March 11, 2009

The good news is that the Obama Administration told Congress that it was committed to drug safety. The bad news is that Budget Director Peter Orszag delivered the news. After going without a Commissioner for half of the Bush Administration, FDA is still without a nominee for commissioner by President Obama.

An interesting article by Reuters is posted on the right under (oddly enough) “Interesting Articles” (Drug Safety…). I’m happy that Congress is concerned about drug safety for imported drugs. I am very unhappy that they aren’t discussing the issue at the same time they are confirming a new Food & Drug Commissioner. FDA needs new leadership committed to public health. Immediately.

Top choices are: Joshua Sharfstein, Baltimore Health Commissioner; Steve Nissen from the Cleveland Clinic, and Center for Drugs mainstay Janet Woodcock. My vote is for new blood (read Sharfstein or Nissen). However, and you need to trust me on this, my opinion counts for very little east of Fife, WA (the state, not the city).

The word on FDA from Tennessee

March 10, 2009

I am currently traveling through Eastern Tennessee and noticed this editorial from the Chattanooga Times about FDA failing to perform its mission of protecting the American People from unsafe food, drugs and medical devices. They are not the only ones to notice that the Bush Administration did FDA no favors when it came to supporting the Agency financially and politically. I like the fact the editorial mentions the failure of “third party” inspectors in the recent peanut crisis.

We need a strong, independent group of FDA inspectors who can do an unbiased job. Unfortunately I have seen some inspectors issue “FDA 483s” that weren’t worth the paper they were printed on. We need to rebuild FDA and we need to start immediately. However, FDA managers need to break out a copy of the regulations and do things “by the book.” Yes, the regulations are in desperate need of updating, but we need the necessary Congressional hearings and stick to the rule making process. A 483 shouldn’t be the product of an inspector’s imagination.

We’ll talk more of poor inspectional findings in the days to come. In the mean time I have posted the editorial under “Interesting Articles to the right. (FDA Woes…)

Blogs on FDA Stuff

March 8, 2009

Obviously I am not the only person with something to say about FDA. A very well organized blog with a lot of good links is Eye on FDA which I am adding to the blogroll at the right. Let me know if you have other blogs worth noting.

So I am editing this because I came across another blog on FDA stuff from another group of lawyers. This is interesting because it discusses the whole issue of FDA regulation of tobacco. The blog is called the FDA law blog and I am adding them onto the blogroll on the right. For a couple of years I was the San Francisco District Tobacco coordinator, which got me a trip to Reno, Tukwilla (Washington State), and… Honolulu. Not difficult duty. I’ll contribute soon on tobacco, because I probably disagree with everybody. Anyway, check out the blog on FDA Law. They have worked hard to put together information for us.

Another interesting blog is Grab and Keel which I have entered onto the blogroll. They discuss food safety issues (the “F” in FDA stands for food, not federal) including a house bill, H.R. 875, that would create a single food safety organization. It is a very good idea and you can check it out on the important references link to the right. Search by bill number when you get to the site.

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