Clinical Trial Compliance & Checklists: The Right Approach?

Update: Checklists and clinical trials are points to consider for clinical trial professionals. I am including a link to some resources you may find of interest. Since I wrote this on January 24, 2010 the post has continued to receive a lot of traffic so I am putting a link to some sites that may be of use to you after reading my original post. One link is Norton Audits and they have a number of documents you can access. The checklist is at the bottom right. The links are at the bottom, scroll down.

Original Post: Checklists and complex medical procedures: Some physicians argue that checklists can reduce infection rates during surgery and help manage an increasingly complex medical system. Also, there is a growing use of checklists in clinical trials including the use of “protocol-specific worksheets” to assist a clinical site in protocol compliance. Some QA specialists think checklists are essential. Others ask, “Is this a good thing? Are we missing something in the checklists?”

The New York Times Book Review reports on the medical part of this discussion in a review by Dr. Sandeep Jauhar entitled “One thing after another,” about the book The Checklist Manifesto” by Dr. Atul Gawande (Metropolitan Books/Henry Holt & Company: $24.50). Dr. Gawande is a professor of surgery at Harvard Medical School and a staff writer at the New Yorker. The reviewer, Dr. Jauhar, is a cardiologist and the author of “Intern: A Doctor’s Initiation.” A quick note: His review does not discuss clinical trials. However, I immediately drew a connection.

An example in the book cites “A five-point checklist implemented in 2001 virtually eradicated central line infections in the intensive care unit at Johns Hopkins hospital, preventing n estimated 43 infetions and eight deaths over 27 months.” That is a very impressive result that has been repeated at studies at intensive care units (ICUs) in Michigan, according to the review.

In clinical trials I have seen many quality assurance audit plans and monitoring procedures that rely heavily on checklists. Checklists are something that I should probably use more. I usually use the FDA Clinical Investigator Compliance Program Guidance Manual (CP 7348.811) that I was trained on when I was at FDA (see link on the right under “FDA Stuff”). However, I see a downside of checklists. Although they help make sure you review the necessary documents hey rarely assist the monitor or auditor in determining significance. I have seen cases where a monitor or auditor has hammered away about an item on their checklist that really wasn’t all that important, or maybe not even relevant for that specific study.
checklist clinical trial
In addition, checklists are entirely dependent on who is writing the checklist and if their list, written in an office complex somewhere, is practical in the field where clinical trials actually are taking place. There can be some serious unintended consequences. I have seen recent FDA Warning Letters to clinical investigators that state:

“A. Your site chose to use the sponsor’s standardized forms as source documents to record and document information related to the subjects’ study visits. Per the standardized form, your site was to “Complete the Inclusion/Exclusion Criteria Worksheet to evaluate for study eligibility.” In the FDA investigator’s review of 16 of 65 subject records at your site, there was no Inclusion/Exclusion Criteria Worksheet found for any of these subjects.”

The records kept at a clinical site are the responsibility of the site, of the clinical investigator, not of the sponsor or the employee that wrote them. If the site doesn’t fill out each of the worksheets, and perhaps sign and date them, then FDA will write you up in a Form FDA 483, Inspectional Observations, for inadequate recordkeeping and possibly a protocol violation. In short, the checklists and worksheets have to be practical to use at the clinical site.

Dr. Jauhar does not talk about clinical trials in his book review. But he does give concrete examples of how checklists can be a problem. For exmple he says:

“Today, insurers are rewarding doctors for using checklists to treat such conditions as heart failure and pneumonia. One item on the pneumonia checklist — that antibiotics be administered to patients within six hours of arrival at the hospital — has been especially problematic. Doctors often cannot diagnose pneumonia that quickly. But with money on the line, there is pressure on doctors to treat, even when the diagnosis isn’t firm. So more and more antibiotics are being used in emergency rooms today, despite the dangers of antibiotic-­resistant bacteria and antibiotic-associated infections.”

The book review is very much worth reading. In addition there is access to a podcast featuring Dr. Gawande. You can find a ink under “Interesting Articles” on the right as well as below:




3 Responses to Clinical Trial Compliance & Checklists: The Right Approach?

  1. rich malloy says:

    Great article and great blog. Thanks. I know that the fda, ema, and especially Dr. Leslie Ball detest chjeck lists, sponsor created “stupid forms” or source dock sheets. Personally I don”t like them either. Allow people to be stupid nad minimalist-they will be so. But, in complex trials, liek one I am about to do, I fer gettign the critical needs documented to a medical record thus I fear source note formats may be all I can offer. any thoughts? Thanks again Carl,

  2. Julie says:

    I enjoyed your article but as an auditor, I am not a fan of Sponsor source docs. More and more I see sites merely ticking check boxes without having support of their response. As Rich noted in his note to you, the sites do become minimalists and uses the excuse with the Sponsor “But you didnt ask for that”!
    Being an ex-inspector, would you respect the integrity of the data documented on those worksheets without support? Thanks J

    • GxP Perspectives says:

      Hi Julie,

      I don’t like sponsor created “protocol-specific worksheets” (my term) either. I caution against calling them “source docs” because my definition of a source document is the original capture of data. It could be on a cocktail napkin. I learned when I was at FDA (from a manager at CBER) to recommend using a site’s “indigenous record keeping system.” Different sponsors come through with different worksheets and the quality of source documentation suffers. I remember one untitled letter from an inspection I did where the compliance officer at CBER wrote, “short, pertinent remarks demonstrate a clinician’s commitment to establishing a clinical baseline,” or something like that (it has been a few years). I also attribute the rise of Notes to File to the practice of sponsor worksheets. The notes to file are a result of poorer source documentation. In answer to your question, it depends on how well the worksheets were designed and if there is anything else, particularly to establish study eligibility. Inclusion/exclusion should be documented with more than a checked box.


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