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.

Super busy

Understaffed and overworked...welcome to any IRB in the country.

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.

Choose the name-brand placebo over the generic placebo

The New York Times is reporting that placebos which cost $2.50 are more effective than the $0.10 version. Yes, this is ridiculous but important at the same time.

Especially in psychiatric studies, the placebo effect shows her head time and time again.

What does this mean for research studies? We should never discredit, or over credit, the role of a placebo. Is it appropriate? It is harmful when proven treatments exist?

I will write more about this topic later and please do not mistake the length of this post as indicative of the complexity of the issue. I could never write enough about placebos in research.

Data Suppression

I'm curious to know what researchers think about data suppression and whether they consider it a human subjects issue, academic ethics issue, or something else.

Howard Brody writes about recent new evidence of pharmaceutical companies practicing data suppression for financial gain. But if pharma can do it, surely an individual investigator could.

Without a doubt, data suppression is difficult to detect from the outside. Big pharma collects data from all of their research sites and analyze, clean, and process data without transparency. To manipulate data is frankly too easy and financially tempting.

As you might imagine, I see this as both a human subjects protections issue and an academic/business ethics issue. Let us not fool ourselves, the University is a business center as much as an educational one.

But before we begin to catch data suppression, we as a research community must agree it is a priority for science and the health care industry, and then we can address who should be responsible for investigation and enforcement.

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.