Informed Consent & Research Ethics Discussed at WIRB Annual Training Seminar

October 2, 2011

Seminar on Informed Consent and Research Ethics

WIRB Training Seminar was Held in Seattle, WA

“Obtaining consent does not make an unethical study ethical,” Dr. Marjorie Speers told the Annual Training Seminar of the Western Institutional Review Board (WIRB). Speers is the President and CEO of AAHRPP (Association for the Accreditation of Human Research Protection Program). She pointed out that, although many IRBs focus on the informed consent process, protocol design is an equally important ethical consideration. The focus of this year’s seminar was informed consent and the speakers’ presentations led to some lively discussion on consent forms, protocol design, research in the developing world, and financial disclosure.

The seminar, which WIRB opens to research professionals in the Puget Sound, features national experts on bioethics and the regulation of IRBs. Among the speakers were Dr. Speers; Dr. Jerry Menikoff, Director of the Office of Human Research Protections (OHRP); Dr. Vincent Ahonkhai, Senior Regulatory Office, Bill and Melinda Gates Foundation; and, Dr. Jeremy Sugarman, Professor of Bioethics and Medicine, Johns Hopkins University. The University of Washington and the Fred Hutchinson Cancer Research Center co-sponsored the seminar with WIRB.

informed consent and research ethics

Simplifying the Informed Consent Process

A recurring theme was the need to shorten consent forms to make them more accessible to research subjects. Dr. Speers referred to most of the required elements of informed consent a “required disclosures,” stating that “disclosures” was a preferrable term. During discussion periods there were several comments that the disclosures had more to do with legal concerns than with involving the research subject in an informed consent process. Dr. Speers stressed that, “too much information is no information.”

Dr. Speers spoke of the need to involve communities as well as the individual research participants. “Communities can be harmed and benefitted by the research,” maintained Speers. “Generally, the public does not understand the drug development process,” Speers said, the aim of gaining new knowledge.

The seminar discussed some humorous examples of researchers not understanding sensibilities in the developing world. For example, informed consent forms frequently use units of measure such as a teaspoon or quarter cup of blood taken for laboratory analysis. However, when the research was in sub-Saharan Africa, because researchers were using units of measurement most common in cooking, potential subjects assumed that the blood was going to be cooked, not analyzed. This led to worries about witchcraft, which was clearly not the intent of the researchers.

WIRB invited a research participant, Debbbie, to address the seminar. Debbie had participated in many cystic fibrosis studies in the past 20 years. She talked about how access to healthcare and money were her primary motivations for participating in a clinical trial. She had lost her health insurance a few months before enrolling in the study. Then she developed pneumonia. During the run-in phase of the study there was a “cleanout” using antibiotics, a common practice in CF studies. Participating in the clinical trial directly benefitted her healthcare. One of the reasons she enjoyed research participation was the access to healthcare and cutting edge developments in the treatment of cystic fibrosis.

The Influence of Money on Research Ethics

Money was a major topic of conversation, as always at a meeting discussing bioethics. Debbie was asked, “how much of a factor is it?” Quite a lot, she replied. Speakers discussed the question from the perspective of financial disclosure. Dr. Speers said that any financial interest by a member of the research team should be an expected disclosure. Others pointed out that the only type of financial relationship that significantly affected potential research participants was when the researchers had an equity interest in the research drug. But not always in ways you might expect. One potential subject said that when learning the PI owned stock in the company sponsoring the research, they thought, “the drug must work,” and wanted to participate.

There was one embarrassing moment for quality assurance professionals during a talk by Dr. Maria Greenwald, a researcher from California. She had recently been audited by a sponsor QA auditor who cited her for failing to report “protocol violations” to the IRB. The protocol required periodic laboratory tests for calcium levels, which were a concern for the investigational product.

Research Ethics and Audit Findings on Calcium Levels

Elevated Calcium Levels

When blood tests revealed significantly increased calcium levels for one research subject, Dr. Greenwald ordered laboratory tests at every study visit, more frequently than the protocol required. She considered this necessary for patient safety using her medical judgment, as required by the Form FDA 1572. The auditor disagreed and insisted that she had violated the protocol.

I remember my own inspection training in the FDA Bioresearch Monitoring program. “Never argue the practice of medicine with an MD,” I was told. When Dr. Greenwald said that she ordered the lab tests for patient safety according to her medical judgment, the auditor should have accepted it and merely noted it in her report.

The public seminar concluded with David Forster, the Chief Compliance Officer for WIRB pointing out a three-page informed consent form approved by WIRB during the first year of its existence. It had all of the required elements, or disclosures, and was simple and to the point. He challenged WIRB board members to see if it was possible to return to a clear, simple consent form. Most appeared up to the challenge.

Carl Anderson
GxP Perspectives
02 October 2011

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Good Documentation Practice: Thanks to Jerry Chapman at IPQ Publications for this useful resource list for GDP Guidance Canon

Information about IPQ Publications

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Next Week: Veteran GCP educator, David Montgomery opines on the
FDA Draft Guidance on Risk-Based Monitoring

Six Weeks Left to Comment on Risk-Based Monitoring!

How to comment to FDA? Here is a two-slide powerpoint presentation on how to comment on the draft guidance document courtesy of CDRH BIMO. Thanks!

Location of Monitoring guidance FR

The Federal Register Docket Number is FDA-2011-D-0597

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Just released– FDA Draft Guidance for Medical Devices: De Novo Classification Process (Evaluation of Automatic Class III Designation)
Read the Federal Register Announcement

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clinical trials FDA monitoring guidanceThere have been some great comments on the GxP Perspectives LinkedIn group on the Draft FDA Risk-Based Monitoring guidance document and on protocol deviations. There is also a new logo for your viewing pleasure. I invite everyone to join the GxP Perspectives LinkedIn Group and join the discussion.

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Pacific Regional Chapter SQA Fall Training 10-11 November at Allergan in Irvine, CA. The training will feature a debate which should be an interesting development in training workshops: Debi Garvin, MS, RQAP-GLP and Paula Parsons: Debate: The role of CAPA in a GLP environment.

PRCSQA Fall Training


Analysis of Recent FDA Warning Letters to IRBs

January 12, 2010

A clear pattern is emerging from the recent spate of IRB Warning Letters written by FDA. It appears that IRB registration is working. The Food & Drug Administration is learning just who is approving research in the U.S.

IRB FDA warning letter
The addition to the FDA IRB regulations, 21 CFR Part 56.106(a), requires Institutional Review Boards (IRBs) reviewing FDA research to register with FDA. It is an excellent addition to the regulations and is already paying dividends to improve clinical trials. (FDA could update a few more regulations but that’s a different story.) Formerly, FDA would only find out about an IRB’s existence if there was an application for a product approval that listed the IRB or if there was a complaint.

Here is a link to the FDA guidance document for Frequently Asked Questions regarding IRB registration:

http://www.fda.gov/downloads/RegulatoryInformation/Guidances/UCM171256.pdf

The ruling went into effect on 14 July 2009 and came on the heels of the Coast IRB sting where the GAO submitted a fake clinical trial that was unwittingly approved by the now defunct Coast. Since that time some very serious Warning Letters have been written citing some very serious violations of regulations designed to protect human participants in clinical trials. At least two IRBs, the Teneo IRB and the MI Hope Inc. DBA Center for Complex Infectious Disease IRB have been told to stop approving studies and to stop enrolling new subjects in existing studies until FDA approves corrective actions. Is there something seriously wrong with IRBs in this country? Reading the Teneo and MI Hope Warning Letters could lead you to think so. Take a look at MI Hope:

UPDATE: Unfortunately FDA doesn’t appear to keep links to Warning Letters active. The ones inserted into this post no longer work. Thanks FDA. You can find the Warning Letters by going to the FDA Warning Letter Page and searching by company.

http://www.fda.gov/ICECI/EnforcementActions/WarningLetters/default.htm#recent

http://www.fda.gov/ICECI/EnforcementActions/WarningLetters/ucm195484.htm

And now Teneo IRB:

http://www.fda.gov/ICECI/EnforcementActions/WarningLetters/ucm191450.htm

Although both these Warning Letters are pretty bad I think that they should have been expected. Previously, FDA did not have the authority to require IRBs to register. Although the work of running a good IRB is quite difficult it amazingly easy to start an “IRB.” It takes five people, one of whom is a scientist (they are not required to be a physician), one a non-scientist, and one not affiliated with the institution. Then you toss in some administrative stuff such as a few written procedures and you’re set to go. As a result, organizations such as MI Hope and Burzynski Research Institute could start their own IRBs free from FDA oversight and with serious potential for conflicts of interest. Now that FDA has a list of these IRBs they are conducting inspections and finding a few bad actors. The same thing happened when FDA started inspecting seafood processors and home respiratory care facilities. The first time FDA comes in to conduct inspections, there frequently are problems. FDA isn’t writing Warning Letters to the many established, legitimate IRBs that have been inspected several times in the past

IRB

Established institutions, such as the Mayo Clinic, have a long history of IRB regulation

When I was at FDA I inspected over 30 IRBs and found that most IRB members were dedicated, hard working research professionals. Most IRB board members are volunteers, serving for no pay or a small stipend. Few people are getting rich at IRBs. Their purpose is to provide independent review of research to protect clinical trial participants. IRBs are a very good thing. Problems sometimes occur when IRBs become confused between FDA regulations and regulations enforced by the Office of Human Research Protections (OHRP). That is what apparently happened recently when a Warning Letter was written to Florida Atlantic University. They are a small academic IRB that reviews very few protocols under FDA jurisdiction. They are significantly different from Teneo, Burzynski, or MI Hope. Take a look for yourself:

http://www.fda.gov/ICECI/EnforcementActions/WarningLetters/ucm195975.htm

As a result, there is a tendency to heap additional responsibilities onto IRBs. Some in Congress are tempted to do this and some “consumer advocates” are as well. This can lead to a stifling effect on innovative research. One principal investigator I know who conducts non-FDA regulated research, primarily through surveys or questionnaires, described IRBs as the “bane of my existence” because of the overly burdensome administrative procedures. These administrative procedures are frequently enacted because OHRP found problems in the past at some academic research institutions. The American Enterprise Institute, a very conservative policy organization, raised some interesting points last year in an opinion peace published in the NY Times (below). We should give FDA the time to wend their way through the list of newly registered IRBs and not have knee-jerk reactions to the initial results. There will be more Warning Letters in the immediate future but that should just weed out the bad actors. Most IRBs have already been inspected by FDA and are doing their work. We need to make their work easier, not more difficult.

Here is a link to the American Enterprise Institute’s op/ed piece:

http://www.aei.org/article/100868

The bottom line is we need legitimate IRBs to independently review clinical research in the United States. We also need to understand that we need research vitality. We should resist the impulse to impose too many restrictions on IRBs.

Read about other FDA Warning Letters:

https://carl1anderson.wordpress.com/category/warning-letters/
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UPDATE: Here is a more recent Warning Letter to an IRB in April 2010. This one appears to be to a smaller IRB that missed a few things. It is different from the ones cited in the story above. Maybe this analysis will need further updating.
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This just in: Request for Comments- Exculpatory Language Used in Informed Consent, a joint FDA and OHRP draft guidance document (September 2011)
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Another IRB, Another FDA Warning Letter

December 11, 2009

FDA Warning Letter IRB

FDA Sends Warning Letter to IRB

FDA is keeping up its scrutiny of IRBs with a Warning Letter to the Burzynski Research Institute IRB. This is a publicly traded, for profit company who decided to run their own Institutional Review Board and dispense with the formalities, and expense, of an independent IRB. The result is a length 8 item Warning Letter listing many serious problems. They include “Failure to determine risks for subjects were minimized and risks to subjects were reasonabable in relation to anticipated benefits.”

I’ve actually never seen this charge before (if my poor memory isn’t failing me) and its a pretty big deal. BRI is a large operation and this is not a very good practice, approving studies of your own research institute that is a for-profit enterprise. I discussed the Warning Letter with a colleague familiar with the operations of IRBs who said, “I’ve never seen FDA look into the details of the (IRB) board’s operations before.” And I haven’t seen the Center for Drugs write so many Warning Letters to IRBs before. Very interesting. (See previous post on the Centra and Teneo Warning Letters.)

The Burzynski IRB Chair, Carlton F. Hazlewood, Ph.D., is also a director of the for-profit research institute, raising concerns about conflicts of interest. In fact, “The IRB failed to ensure that no member participated in the initial or continuing review of a project in which the member had a conflicting interest,” is the fourth charge in the Warning Letter. The IRB would also allow non-members to vote if a board member had a conflict. Thats another big problem. There are very specific rules about the membership of an IRB.

The company is run by physician and researcher Stanislaw Burzynski, MD, PhD who has been the President and Chairman of the Board of Directors of the Burzynski Research Institute since its inception in 1984. Read the Warning Letter for yourself. Here is the URL, (WordPress isn’t letting me insert a link):

http://www.fda.gov/ICECI/EnforcementActions/WarningLetters/ucm192711.htm

http://www.fda.gov/ICECI/EnforcementActions/WarningLetters/ucm192711.htm


Centra & Teneo IRBs Receive FDA Warning Letters

November 28, 2009

The FDA Warning Letter to the Teneo IRB is an interesting for several reasons. First, the Center for Biologics, FDA’s smallest for human clinical trial regulation, wrote the Warning Letter and they don’t do that frequently to IRBs. Second, the IRB was found to have two sets of meeting minutes in an effort to keep some activities out of the regulatory realm. Third, FDA told the IRB to stop approving studies or having current studies enroll new subjects “until adequate correction is made.” This is about as tough as it gets for an IRB. I am attaching a Thompson link about the Warning Letter. Now I am going to take a break from blogging (I think).

IRB FDA warning letter

Two IRBs receive FDA Warning Letters


Update: Another IRB, another Warning Letter. Centra IRB in Lynchburg, VA received a Warning Letter dated 20 November 09 from the Center for Devices. These folks violated a couple of Big Deals about IRB review of research. First, they forgot to review approved studies after a year. Remember the “Tuskegee Syphilis Study?” What went wrong there was no continuing review of research. Even after they discovered that penicillin worked wonders on syphilis. Then Centra forgot how many people were needed for a quorum. You need a minimum number of IRB members to approve research. Then they forgot to write down what they did. Their minutes didn’t describe what happened at the meetings. If you didn’t document it then its just a rumor. These are basic things that anyone in the IRB business should know about. Read for yourself on the FDA Warning Letter webpage.

http://www.fda.gov/ICECI/EnforcementActions/WarningLetters/default.htm

Comparing FDA & EMEA Requirements for Clinical Trials & Pharmacovigilance: I will be presenting an audio-conference for Thompson Interactive on this topic on March 3rd. Here is a link for further information:

http://www.thompsoninteractive.com/site/offer.jsp?promo=FDAR3KC0&priority=FKYG54693


Clinical trials recruitment and the fight against cancer: Update

August 4, 2009

A couple of years ago Applied Clinical Trials magazine ran a survey on the most troublesome aspect of conducting clinical trials. There were about a dozen different categories listed including government regulations. However, the number one choice, of nearly half the respondents (clinical trial professionals), was the difficulty in recruiting subjects/participants to the studies. Now the New York Times has connected the problem with recruitment of clinical trial volunteers to the war against cancer (see Blogroll: 123 NY Times…).

There is one very big mistake in the article. The claim is made that each “adverse reaction” needs to be reported to the institutional review board (IRB) for evaluation and that each participant needs to be notified, regardless if the event is related to the study drug or is the progression of the disease. This just isn’t true. And the misunderstanding about reporting adverse drug or device events causes a lot of problems for people involved with conducting clinical trials.

If you read the FDA regulations in 21 CFR 312.66 it says that the researcher, “…will promptly report to the IRB all changes in the research activity and all unanticipated problems involving risk to human subjects or others…”

This is very different than reporting the progression of the disease, or stubbing one’s toe. There is a lot of confusion about defining and reporting adverse events to IRBs. Some IRBs will refuse to accept anything unless it meets the standard of “unanticipated problems involving risk to human subjects.” Other IRBs, those without much experience, demand all adverse events or all serious adverse events (SAEs as defined by FDA regulations) be reported. This isn’t helpful and it really isn’t helpful that many clinical trial sponsors or contract research organizations require over-reporting “just to be safe.” The whole purpose of expedited reporting of an unanticipated problem is to bring it to the attention of the IRB. If the IRB is inundated with with unrelated events, then the real problems, that require the IRB’s attention, get lost in the flood of paperwork.

FDA regulations and guidance documents are in serious need of updating. How to defne and report adverse events would be a very good place to start.

UPDATE: I did actually try to get a letter published by the Times. But you know how that goes. Its one of the reasons I have a blog. Here it is for those who are interested:

“Lack of Study Participants Said To Hobble Fight Against Cancer” repeats a common misunderstanding about reporting adverse events to an institutional review board (IRB). The article states that every time a patient has an adverse reaction that participating medical centers needed to inform each study participant and respond to the IRB, even if the reaction is unrelated to the drug and due to disease progression. Nothing could be further than the truth. FDA regulations only require reporting “all unanticipated problems involving risk.”*

Disease progression in a cancer clinical trial can hardly be described as an unanticipated problem. The over-reporting of adverse events to IRBs is a major problem clogging research activities. Reporting each adverse event defeats the purpose of expedited reporting when there really is a problem. Actual unanticipated problems are lost in the mountain of routine reports. There are several reasons for this.

The first is that many IRBs and sponsors of clinical trials incorrectly believe that all adverse events need to be reported. FDA has not had the resources to effectively communicate requirements for safety reporting. Next, there are confusing, multiple definitions for adverse event, adverse experience, and adverse reaction. Finally, FDA’s clinical trial regulations were written in the 1970s, are outdated, and sometimes conflict with the regulations of the U.S. Office of Human Research Protections.

One obvious solution is to give FDA the resources and support necessary to update their regulations and guidance documents, coordinate them with other agencies, and then consistently apply them during inspections.

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Life after the Coast IRB sting: What should we do about IRBs?

July 21, 2009

I was discussing the Coast IRB sting operation by the Government Accountability Office (GAO) with some quality assurance colleagues the other day. Quality Assurance departments at biopharmaceutical and medical device companies are starting to scrutinize the institutional review boards (IRBs) that they contract with or that clinical sites use to review research. FDA requires sponsors to obtain assurances from clinical investigators (on the Form FDA 1572 or Investigator’s Agreement) that they will obtain approval from an IRB that meets the requirements of 21 CFR Part 56 (the IRB regulations).

The closure of Coast IRB impacted approximately 300 clinical trials and 3,000 clinical sites conducting the studies. Coast had approved a phony study submitted to them by the GAO. Two other IRBs refused to approve the study but Coast did. They are now out of business and a lot of people are scrambling to make sure their studies and their data aren’t negatively impacted by the closure. It is understandable that there is considerable concern. However, there will be a lot of false assumptions made by the Coast sting and a lot of wrong conclusions drawn from the case. Here are some of my preliminary thoughts:

1. The IRB regulations are hopelessly outdated. When they were written commercial IRBs like Coast weren’t really imagined, let alone accounted for. IRBs were supposed to be ethics committees for a specific institution at a specific location, such as an academic medical center. They were led by volunteers and there frequently wasn’t even an administrative fee for submission of a protocol. They were also slow and cumbersome. That’s one of the reasons commercial IRBs came into existence.

To make matters worse, IRBs are regulated both by FDA and the Office of Human Research Protection (OHRP), in the Department of Health and Human Services for NIH and other government funded research. Although the regulations are very similar, there are some differences and OHRP regulates IRBs much differently than FDA. Most academic medical centers depend on NIH funding so they follow the OHRP regulations very closely.

2. The regulatory relationship is between the investigator and the IRB, not between the sponsor and IRB. Many of the traditional institution based IRBs won’t even talk to the sponsor. However, things have changed. Many studies are conducted outside of the traditional institutional setting and many sponsors prefer to work with a commercial IRB because they are faster and, in the opinion of many, more efficient. Clinical trials are expensive and the ability to work directly with an IRB on informed consent forms and protocol amendments is very appealing to sponsors and investigators alike.

3. IRBs aren’t supposed to monitor clinical trials, sponsors are. However, many are suggesting more and more responsibilities be assigned to the IRB. This can be a problem for a variety of reasons. An academic IRB may be slower if OHRP decides to enforce regulations in a strict manner. Their funding depends on it. NIH can put stricter enforcement standards in their proposals. For FDA to require commercial IRBs to do more supervision there would need to be a revision of the regulations. That can take a lot of time.

In the mean time, sponsors are wondering how they qualify and supervise their contract IRBs. There is only one place that gives them any clout in FDA guidance documents and regulations. The very last sentence of Section 3 in E6, Combined Guidance for Good Clinical Practice states the following:

“The IRB/IEC may be asked by investigators, sponsors, or regulatory authorities to provide copies of its written procedures and membership lists.”

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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.


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