IRB Tip: Genetic Anaylses

If genetic analyses will be performed, I suggest you address the following in the cover letter and clarify these issues in the revised IRB application:

1. Describe the analyses that will be conducted on the saliva samples, and the genetic markers that will be analyzed.

2. Clarify the purpose of the genetic testing in this study and revise the Protocol Summary.

3. Clarify in the application and consent form whether subjects will receive their results from the genetic testing.

a. If so, clarify whether the genetic tests to be conducted have been scientifically validated and whether the lab where the testing will take place is CLIA certified.

i. If not, provide an ethical justification for providing subjects with their results from the genetic testing.

b. If not, revise the consent form to indicate that subjects will not be provided with their results from the genetic testing.

4. Revise the application to include background information regarding the genetic testing to be conducted in this study.

5. Clarify in the application and consent form whether there are potential benefits to society as a result of the genetic testing to be conducted in this study.

IRB Tip: Deferral avoidance for recruitment

Deferred is a categorization which an IRB gives a study after it has been reviewed by the Board and found to have significantly unclear or missing study procedures and/or goals. Most deferrals, believe it or not, are avoidable. Unfortunately, few on the research-side know how to accomplish this.

From time to time I think (mistakenly) that I could make a lot of money by helping biopharma or some for-profit consulting group manipulate the IRB review system such that as an IRB consultant I could prevent all studies I touched avoid deferral. Such an attitude is really quite silly. Like individuals, IRBs develop tendencies--personalities if you will--which cannot be predicted with 100% accuracy.

But I do believe I think I know my IRB pretty well and with that, another IRB tip.

When describing how you will recruit subjects for your study, it should almost never be just one sentence.

You would be surprised how many studies come across my desk with just this weakness.

You need not describe every second of the recruitment process, but you should describe it such that a reader who is unfamiliar with your project could envision when and how you identify, approach, screen, and enlist a prospective subject up to her signing the consent form.

There are some areas of an IRB application that you could be lazy and get away with it. However, recruitment procedures are not one of them. It's okay to use bullets, paragraphs, or even comic strip depictions--but clearly describe recruitment.

Suppose you are recruiting subjects directly in the context of clinical (non-research) procedures This is pretty common in medical research: You'd like to enroll your own patients in your study. Coercion, however, is a real concern. In other words, are your patients feeling pressure (real or imagined) to participate in a study for which you are both treating health care provider and researcher?

I recommend the following when recruiting subjects who are also patients: (1) Provide a study flyer, (2) recommend your patient review the flyer at home and talk to family members and/or friends about participating, (3) call the study team at the number on the flyer if interested in the study.

In this way, a prospective subject's real or perceived pressure to join your study is minimized. Of course, some patients will want to participate in your study straight away. And that is okay. Simply describe in the IRB application that if a patient asks to join the study during her clinical appointment, this will be clearly documented in her medical record.

Last but not least, include the following language (or something similar) on the first page of your consent form:

Disclosure Statement
Your health care provider may be an investigator of this research protocol, and as an investigator, is interested in both your clinical welfare and in the conduct of this study. Before entering this study or at any time during the research, you may ask for a second opinion about your care from another doctor who is in no way associated with this project. You are not under any obligation to participate in any research project offered by your physician.

FDA & suicide

I haven't decided whether it's good or bad (I lean to the latter) that the FDA recently announced "findings" in studies involving antiepileptic drugs an increased report of suicidal ideation.

An FDA analysis of suicidality reports from placebo-controlled studies of 11 antiepileptic drugs shows that patients taking these drugs have about twice the risk of suicidal thoughts and behaviors (0.43 percent), compared with patients receiving placebo (0.22 percent). This risk corresponds to an estimated 2.1 per 1,000 more patients in the drug treatment groups who experienced suicidality than in the placebo groups.

Keep in mind, these are not big numbers. But when it comes to risk ratios, for researchers, it's the comparison that matters (0.43 vs. 0.22). It translates to twice the risk!

Scary! Fear! Boogeyman!

It would not be surprising--given FDA is inherently political despite their best intentions--that soon research studies involving any antiepileptics will require procedures for addressing situations in which subjects exhibit suicidal thoughts. Again, I'm not convinced this is bad necessarily, but it is yet another issue researchers will need to be aware of when preparing their research applications and another item to be added to the consent form.

As far as suicide procedures, this is what IRBs like to see:

- A qualified individual should evaluate all subjects whose responses indicate that they may be suicidal.

- Potentially suicidal subjects should be referred for appropriate clinical care. Please outline your procedures for ensuring that all potentially suicidal subjects are provided with referrals for appropriate clinical care.

- If a subject is acutely suicidal, they should be transported to the emergency room by trained personnel and a trained member of the study staff should remain with the subject until they have been transferred.

And then, in the consent form, languages something like this:

In the event that you tell the research staff that you are thinking about killing yourself or you answer “yes” to a question about having thoughts about suicide, the investigator will ask you more questions about the thoughts. Depending on how intense your thoughts are or how much you feel like hurting yourself, the research staff may provide you with referrals for treatment, work with you to contact your personal physician, trusted family member, or therapist to discuss your thoughts of harming yourself; or work with you on a plan that may include getting you to a hospital for safety.

Don't hate me me for this. If and when the time comes, complain to the FDA.

IRB Tip #2: HIPAA

Old school medical researchers (and social-behavioral, for that matter) find HIPAA the bane of their collective existences. Codified into federal law in 1996, HIPAA established national standards for health care insurance portability and patient privacy rights. From the researcher point of view, she could no longer simply open a medical record and review it for research purposes without written permission from the patient-subject or a waiver by a privacy board / IRB.

Patient advocates rejoiced. And despite being on the research side at the time, I celebrated too. How dare I, you ask? What self-respecting researcher likes HIPAA?

Frankly, I'm a big believer of individual rights. And this is a clear-as-day issue of individual rights.

Unfortunately, then states' rights ruled the day when it came to patient privacy. These rights were not consistent from state to state and depending on where you lived, someone could take a peak in your medical record without your permission. HIPAA ensures patient-subject rights to some degree. IRBs are often the entities which review requests to open medical records in a research setting.

Regardless of your feelings about HIPAA, I bet we'll agree on something HIPAA related: our HIPAA Research Application (HRA) is terrible. It is perhaps the worst form we have next to the Internal Adverse Event report form. More on that another time. Back to the HRA.

First the 4 page application is backwards. The first determination investigators must make is, "When will I look at the medical record?" If the answer is to enroll subjects, without first obtaining their permission, you will want to ask for a waiver of HIPAA and informed consent for research purposes. Respond to Section B (on Page 2 of the application), Section II.B (on page 1), Section I.A, I.B, I.C (also on page 1). Asking for a waiver of HIPAA will also lead you to complete section B.1-B.4 as appropriate.

If you will be reviewing the medical record only after obtaining signed informed consent, complete Section I.A, I.B, I.C (on page 1) and Section A (on page 2) by writing, "I assure the Board I will use the UCLA HIPAA authorization form and IRB approved informed consent form."

If at any time you add research information to the medical record, more often than not you must get HIPAA authorization and obtained signed informed consent to do so. This means complete Section I.A, I.B, I.C (on page 1) and Section A (on page 2) by writing, "I assure the Board I will use the UCLA HIPAA authorization form and IRB approved informed consent form."

IRB Tip #1

One of the reasons for starting this blog was to help investigators and research assistants and coordinators in an unofficial way. Don't get me wrong, I think I'm a pretty helpful guy in real life, but there are limits to what is proper in an official setting.

However, this blog gives me a good opportunity to expose the "secrets" of IRB functionality. And they really aren't secrets at all. But my sense is that IRBs generally do a poor job of educating, and researchers do a poor job of passing on information from staff to staff due to high turnover. Let's be honest, some (many?) PIs know little to nothing about an IRB submission and they can't teach their staffs what they don't know.

Although the idea here is for most tips to be specific to the IRB I know best, other IRBs follow similar policies. These policies, after all, have basis in federal regulations. Still, it's remarkable even to me--a "professional"--how varying IRBs work from institution from institution. Nevertheless, I will try to provide helpful tips to readers of this blog as best as I am able. Contact your own IRB for specific consideration. And feel free to let me know if their handling/processing is different from what I've described.

And with that, my first IRB Tip of GTMR:

IRB Tip #1
When your IRB takes forever to review and approve a new study, and you just want "administrative approval," you can get it pretty easily but only if you haven't submitted the full IRB application already.

Federal regulations (45 CFR 46.118) permit approval of a study prior to review by the IRB when "lacking definitive plans for involvement of human subjects."

This is a particularly good option when you can't access your grant money until IRB approval is obtained or if you're applying for a Certificate of Confidentiality from the NIH. Sometimes the NIH accepts it, other times they don't. But when it takes 3 months to get a CoC, it's worth trying to apply early, isn't it?

Frankly, I think many investigators should request administrative approval under 45 CFR 46.118, especially if your IRB is notorious for being slow or "picky."

Here's how you do it: In a simple letter, explain that you've been awarded X grant and wish to prepare the IRB application but cannot until you get IRB approval to release those funds. Provide your assurance that you will not initiate research involving human subjects until you obtain prospective IRB approval. State the title of the grant, the title of the study, and include a copy of the grant application (the protocol is sufficient). Complete the first 2 pages of the IRB application. Turn it in. That's it. Really. IRB approval is on its way. You can thank me another time.