Trial by Coercion?

'Coercion' is a word sponsors of clinical trials never want used to describe their treatment of participants. Why? I can think of at least three reasons. It runs counter to federal regulations governing clinical research. It certainly isn't good for public relations. And it makes it difficult to recruit volunteers for future studies.

Coercive situations range from the merely questionable to the outright illegal, bordering on evil. Some ethicists would argue that any payment for participation in a clinical trial (other than simply reimbursing for expenses such as transportation to and from a clinic) may induce someone to volunteer for a study, possibly putting themselves at risk, when they would not ordinarily do so. If the individual would not normally take the risk, then the payment could be considered coercive. On the other end of the spectrum is the nursing home resident who is told her family wants her to participate and, if she doesn't, family members will be angry with her and may stop visiting.

Take the recently-reported allegations against a large for-profit clinical testing center, SFBC International, Inc. Bloomberg.com reported in November that research participants complained that they were threatened with deportation (the volunteer participants were immigrants living in Florida) if they did not sign statements retracting their initial responses to questions from journalists about their clinical trial experiences. Whether or not officials of SFBC did, in fact, make such threats is irrelevant. SFBC has reportedly agreed to meet with staff of Senate Finance Committee Chairman Charles Grassley concerning clinical trial practices in general. In any case, if such threats were made or even implied, they would constitute a coercive behavior.

Think about it. If research participants are 'volunteering' because they are being threatened, then their participation is not really voluntary at all. And if their responses to questions concerning their clinical trial experience are being shaped by the circumstances under which they are being questioned, then the science goes completely out the window because their answers are not freely given.

Coercion in clinical research is poor policy and lousy science. Such practices are not common, thankfully. But, if you are a clinical trial participant and feel you are being coerced, either bring your concern to the attention of the research team or the Institutional Review Board (IRB) overseeing the study... or withdraw from the study.

-Joe

Related Topics: Ethics and Medical Research Can Go Hand in Hand, Clinical Trials: Are they safe?

Tags: coercion,clinical trials,research,volunteers

The Institutional Review Board (IRB)

They used to be called 'Ethics Boards,' and they were tasked with deciding when a particular patient would not be resuscitated, which patient was next in line to receive a kidney transplant, and how a hospital's policy defined 'brain death.' Hospitals and other medical facilities had them -- and used them to make the tough decisions. As clinical research became a more organized practice, evolving from simply trying a new procedure on a particularly (usually terminally) ill patient to detailed protocols involving many ill participants matched with healthy ones, one of the more demanding tasks of the Ethics Boards became reviewing proposed research before it was allowed to be conducted at an institution. The result was a subcommittee of sorts, which came to be called the Institutional Review Board or IRB.

Typically, the early IRBs comprised the most senior physicians at an institution, a top level administrator or two, perhaps the institution's attorney and chaplain, and a couple of physicians who conducted research -- often the very research the IRB was charged with reviewing. We've come a long way since these early IRBs. Now there is much greater standardization and regulation of the IRB's composition and responsibilities. And because of conflict of interest concerns, clinical investigators are not usually allowed to participate as IRB members reviewing their own clinical trial protocols. IRBs are populated with physicians, scientists, ethicists, patient advocates, and members of the communities in which the clinical research will be conducted. They must possess sufficient expertise to be able to adequately review the science and the medicine of the proposed research. Detailed written records of the IRB's discussions, decisions and actions are maintained. And they are responsible not only for determining whether or not a protocol will be approved, but the conditions to be imposed on it, as well as for monitoring the progress of the clinical trial, including changes, adverse events, and results. Finally, the IRB is the institution's ultimate decision-maker when it comes to shutting down a clinical trial or dealing with the aftermath of a clinical trial that unexpectedly harms participants.

Are IRB's perfect? Definitely not. They are sometimes understaffed, inexperienced or overburdened with a large volume of clinical trials to review. But they are better now than they have ever been and they are improving steadily. It is uniformly accepted that the IRB's primary concern should be for the protection of participants, even when that concern may create administrative hurdles for potential physician investigators or prevent the institution from accepting funding for certain clinical research. In that sense, today's IRB still provides an 'ethical check' on clinical trials conducted in hospitals, universities and medical institutions.

-Joe

Related Topics: Stem Cell Research, Organ Transplants

The Blind Study

Most clinical trials can be improved by designing them as blinded, rather than non-blinded studies. Perhaps not the most PC description. "Blinding" simply refers to the fact that, during a study, the investigator or the participant or both are not aware which one of two or more experimental procedures the participant is undergoing.

Let's say I have volunteered to participate in a clinical trial of a new diet pill (not that I need to lose weight, you understand!). The study is set up such that I could be randomly put into any one of three experimental groups. If I'm in Group 1, I would take one capsule containing the new diet drug. If I'm in Group 2, I would take a similar-looking capsule which contained an existing diet drug. And if I'm in Group 3, I would take a capsule containing an inactive powder (a placebo). By comparing results of the three treatment groups, the investigators hope to draw some conclusions about how effective the new diet drug is.

If I am not told which Group I am in, then I am said to be "blinded," and the study is called a "single blind" study. If neither I nor the investigator who is taking measurements (such as my weight and waist size) during the study knows which Group I've been put in, then the study is said to be a "double blind." Of course, the study team has records showing which Group I was in, and I will be told which Group I was in when the clinical trial is finished.

I'll discuss why such blinding is important to many clinical trials in a future blog.

-Joe

Related Topics: Informed Consent, Clinical Trials Quiz

ClinicalTrials.gov

It's about time. For years, information about clinical trials, especially those designed to study a prospective or marketed medical product, was kept under close wraps. It is understandable that a company investing tens-of-millions of dollars to develop a potential drug to treat psoriasis or a new surgical device would not want to divulge details of a clinical trial that proved its product to be less effective than a competitor's. Most companies wouldn't want to risk discouraging investors by publicizing a failed clinical trial. But the spotlight on clinical trials is gradually being intensified, due to pressure from medical journal editors, the U.S. Food and Drug Administration, academic medical centers, and medical societies.

One such source of exposure is the ClinicalTrials.gov web site. Its purpose is to provide a location at which certain standard information about clinical trials may be published. The site, which consists mainly of a searchable database of clinical trials, currently contains over 20,000 listings. It allows the clinical trials to be browsed by condition (such as diabetes or cancer or autism), by sponsor (the National Institutes of Health, companies, universities), or by status (recruitment closed or open). It also is set up to be searched by specific parameters such as the study's location or eligible age range of participants.

While not anywhere near all clinical trials are listed, ClinicalTrials.Gov provides an obvious information resource to consumers and researchers. More than that, however, this site, along with requirements by certain medical journals and sponsors (such as the National Institutes of Health) that clinical trials be published, is a first step toward assuring that the studies are reported accurately and do not simply disappear into thin air without being reported. Even if a clinical trial does not demonstrate that a particular treatment is beneficial -- perhaps especially if a particular treatment is demonstrated to be detrimental -- it is important for medical researchers, clinicians and patients to know what has been learned. Otherwise time, effort and resources are wasted and people are put at unnecessary risk testing an idea that has already proven to be a bad one. I foresee the day when all clinical trials, regardless of who sponsors or conducts them, will be required to be posted from the time they are approved to begin all the through the publication of results. And that... would be a good thing.

-Joe

Related Topics: Clinical Trials, Clinical Trial Questions

Children In Clinical Trials?

One hallmark of ethical clinical research is that participants have a full understanding of the research, including its relative risks and benefits. Participation in a clinical trial cannot really be considered voluntary without complete knowledge and acceptance of what is going to happen. Children, depending upon their intellectual maturity, may or may not be capable of truly understanding the complexities of clinical research. For that reason, children are not usually allowed to decide for themselves that they will volunteer for a clinical trial. Instead, the consent of a parent or guardian is required.

Eighteen is the most commonly accepted age of adulthood, although in some places younger individuals are allowed to decide for themselves. Many clinical trials require, in addition to the written consent of a parent or guardian, the assent of the child herself, if she is able to understand what will be happening to her. In practice, this usually means that a child who indicates he does not wish to participate, by vocalizing or otherwise objecting, is not enrolled into a study except under exceptional circumstances (for example, where the child will surely die if the experimental procedure is not attempted).

What does this really mean, then? Well, it means that, as usual, children don't have much control over this aspect of their lives. This is certainly not a new concept, given that children cannot enter into certain contracts, they cannot serve in the military or vote, and they cannot buy alcohol or tobacco products. There are obvious reasons for imposing these restrictions on children – they are being protected from harm at a time in their lives when they are considered vulnerable. The same holds true for volunteering for clinical trials.

Here's the bad news: Some medications that have been routinely prescribed for children were never tested in children before being marketed. More on this aspect of children in clinical trials in my next entry...

-Joe

Related Topics: Clinical Trials: Too Many Minority Kids, Testing Children's Drugs on Children

What's Being Done About Bird Flu?

We're hearing about how it's only a matter of time before a world-wide pandemic of flu hits, killing perhaps hundreds of thousands of people. The flu virus, which lives in birds, has recently infected humans handling the birds (mainly chickens) in Asia and eastern Europe. The number of deaths from this bird or avian flu is rising as the flu spreads westward. But the real concern is that the flu virus may mutate (as flu viruses often do) into a strain that is passed easily from human to human, rather than just from birds to humans who are in close contact with the birds. If that were to happen, what could be done? The same thing we do whenever we have a reason to believe a virus or other infectious pest is on the way: we vaccinate.

Not only are vaccines being developed against the type of bird flu that is most prevalent, they are already being tested in humans. One of the institutions testing a vaccine is the Johns Hopkins University School of Public Health in Baltimore. 70 healthy participants are being recruited to receive the vaccine in a nasal spray. The volunteer participants will stay in the hospital for observation and to have blood samples and nasal washes collected daily for at least two weeks from the day on which they receive the vaccine. This is what is known as a Phase I study, which looks primarily at the safety of the treatment (in this case, the vaccine), but also looks at how well the vaccine works. Bad reactions to the vaccine will be monitored (and treated, of course), and measurements will be taken to see how much immunity to the flu virus is generated in each participant.

Results of this clinical trial will tell us whether or not this particular vaccine is worth testing further as a safe way of protecting people against a flu outbreak. If results are promising, then the next phase of clinical trials (Phase II) will involve larger numbers of participants and will focus more on whether the vaccine actually protects individuals who are exposed to the flu from getting sick. Yes – that means participants will be vaccinated, then they will be exposed to the flu and observed to see whether or not they become ill.

It all takes time, money, medical and scientific expertise, and volunteer participants... Damn birds.

-Joe

Related Topics: Special Report: Bird Flu, Avian Flu in Vietnam