Ignorance is No Excuse

John Serio, a licensed pharmacist and associate in the corporate practice of the Boston-based law firm Brown Rudnick Berlack Israels, co-authored a state-by-state clinical trials requirements reference guide to help sponsors map out their research strategies. In this interview, he explains how critical it is to stay on top of the nuanced differences among state laws-everything from informed consent to IRB composition. Ultimately, it's sponsors' responsibility to be compliant.

John Serio

Pharm Exec: What's driving states' involvement in clinical research?

Serio: Most [state clinical trials requirements] are there to protect those that can't necessarily protect themselves. And not that most ethical pharmaceutical companies exploit people in clinical trials; most of them are clearly concerned with providing therapeutics that may help them. But there are companies out there, big and small, that perhaps sometimes along the way, the care of the patient maybe gets lost. So that's probably the biggest driver. Most of these [requirements] are there to protect people from being exploited, because unfortunately, during the history of clinical trials, there are numerous instances where people have been used and unsafely exposed to compounds. Forty years later, it's easy to say, "How did this happen?" Many of these state statutes are in place because of things like the syphilis study down in the South many, many years ago, the Fernald School in Massachusetts, even the gene therapy study as recently as just several years ago, where a fairly healthy person ended up dying. And so as new therapeutics emerge, as we pursue more biologics or gene therapy, [these statutes] will prevent people who are not capable of defending their own rights from being exploited.

How familiar are companies with the differences among states in these different areas?

Not too familiar. Most companies think that as long as they're in compliance with federal rules, they're fine. But when something goes wrong in the conduct of a clinical trial, all of a sudden plaintiffs' attorneys start looking at how they were conducted. Also, all of the healthcare professionals involved in clinical trials are licensed by the state in which they practice. So when one starts looking at how a trial was conducted, the first thing that they look at are consenting issues. That's why you need to make sure that you consent participants in accordance with state and federal law.

How much do informed consent requirements differ from state to state? How important of a consideration is that?

Informed consent is the foundation of any good clinical trial. And the ability to consent typically is determined by state law. There are certain requirements within federal regulations for what an informed consent needs to contain—a brief description of the clinical trial, alternative treatments, the risk involved in the trial, your right to withdraw, etcetera. All of that is assuming that you in fact have the ability to consent for yourself. Where state laws come into play is perhaps in special populations: prisoners, people in state custody or in state institutions, people who have diminished mental capacity, children who are wards of the state or in the custody of foster parents. Often, state laws determine parties' ability to consent.

How important are these differences among states when companies recruit patients?

It's something to add to the list of considerations. If you are conducting trials in a particular state, you'd better understand the nuances of its laws. Especially when you're in particular areas of concern, like AIDS testing. Almost every state has very specific requirements about counseling before and after, and about confidentiality of the results. Companies need to understand these requirements if AIDS testing is going to be part of a trial.

There are other differences, even things such as who is allowed to handle experimental therapies. Typically, hospital pharmacies can handle them, but the products often have to be labeled in a particular way. Sponsors should know state licensing authorities. If you are engaging various principal investigators, you want to make sure that you know their history and that they're members in good standing. You don't want to conduct a trial and then find out that you have been using somebody who has a history of discipline, or who may not even have a license.

Some states have particular requirements for IRBs, which review protocols before allowing clinical trials to move forward. Some states require certain makeups of IRBs, that a certain number of professionals or certain level of diversity must exist in order for that IRB to be in compliance with state law. So if you work with an IRB that is not in compliance with state law and it approves your clinical trial, and somebody is hurt within the conduct of that trial, you have exposed yourself to liability.

What trends do you see in states' involvement in clinical research?

The trend is that these state laws are going to become more important. In some states, like Massachusetts, for instance, a protocol approved by an IRB is reviewed by the state Department of Health as a matter of procedure. And they do that in case, all of a sudden, they see an influx of clinical trials in an area that may generate some moral or legal concern.

California is a very interesting state—it has the most regulations regarding clinical trials. Some of those are to sponsors' advantage, in that cancer therapies are greatly favored. You can actually conduct early phases of clinical trials in California without going through the FDA. It has its own Cancer Act that encourages research in cancer therapeutics. So California is a very proactive state in that regard, as it is for AIDS treatments. But it's also very conservative, in that if you're going to conduct a trial on any controlled substance—any scheduled drug—you have to have that clinical study reviewed by a review board that is under the authority of the state's Attorney General office. So if you start a trial with a controlled substance without approval, you can find that trial shut down halfway through. In California, clinical trial subjects must be given a copy of the patient bill of rights that explains their rights and responsibilities.

Most companies understand these regulations because they use local practitioners who are sensitive to them. And so from a strategic perspective, it's advantageous to choose a state that offers incentives or rewards for companies conducting trials in your particular area of interest or research. In some states, the cost of conducting trials will be lower, because health insurers are mandated to reimburse for general and routine costs involved in trials for those select therapies.

From a liability perspective, as a sponsor of clinical trials, you want to make sure that you're not being overly exposed to liability because you have not necessarily secured proper consent. In some states, consent forms only have a life span of so many months. In Wisconsin, for example, a consent is only good for 18 months. So if you have a long-term study, you need to make sure that you're reconsenting people every year and a half.