Why Did She Do It?

At first, I couldn't figure out why Jolee Mohr would take the advice of her rheumatologist, Dr Robert Trapp, and volunteer for a clinical trial of an experimental drug for inflammatory arthritis.

Jolee suffered from chronic inflammatory arthritis, a painful joint condition. Targeted Genetics Corporation, a molecular therapeutics company based in Seattle, was conducting a clinical trial of one of its pipeline gene therapy drugs - tgAAC94. The study was an early-phase study, primarily intended to test the safety of the drug. If it proved to be safe in humans, then further clinical trials would presumably be designed and conducted to demonstrate its effectiveness in relieving the symptoms of inflammatory arthritis.

The protocol called for participants to receive two injections, several months apart. The first treatment would be either the drug or a placebo, decided by chance according to the study design. The participant would not know which she had received. The second injection would be the drug for sure. Jolee received her first injection last February, with no significant side effects. Her second injection was administered by Dr. Trapp on July 2. On July 24 Jolee died of an unexplained massive infection.

The clinical trial has been suspended. The company and the Food and Drug Administration (FDA) are investigating. Jolee's husband and young daughter are left behind.

It is too early too tell for sure whether or not the tgAAC94 was the cause of Jolee's death, although the fact that she developed symptoms leading to her death very soon after receiving the second injection suggests a connection.

What I wondered, though, is why Jolee volunteered for the clinical trial in the first place? Why?
Because, even though there was a sentence in the 15-page consent form which stated that participants were not expected to receive any direct medical benefit from the drug, she believed there was a chance tgACC94 would help her. She believed this because scientists and physicians were developing this compound and had designed the study. Because the study was reviewed and approved by an Institutional Review Board and was being overseen by the FDA. And because her doctor, Robert Trapp, recommended it.

She didn't have a chance.

~Joe

Related Topics:

• Arthritis Clinical Trials: A Guide for Patients
• Clinical Trials: Benefits and Risks

Technorati Tags: Jolee Mohr, Targeted Genetics Corporation, Dr. Robert Trapp, clinical trials, FDA, gene therapy

Is Someone In Your Inner Circle Making You Fat?

One of the most highly-publicized clinical trials in recent history was published last month in The New England Journal of Medicine. The results of the study, conducted by Dr. Nicholas Christakis at Harvard Medical School and his colleague Dr. James Fowler at the University of California San Diego, suggest that obesity is spread among people having close relationships with one another.

Several thousand people in Massachusetts were studied over a 32-year period. Those who had a very close friend, a sibling or a spouse who became obese had a better chance of becoming obese than those who did not have a close relationship with someone who became obese. The risk increased by 30-60%, in fact!

This is not to suggest that obesity is spread in some kind of communicable way, although the authors did not totally dismiss that possibility. Rather, the research supports the idea that our social network - those people who are closest to us emotionally - influences whether or not we gain large amounts of weight.

The paper also gives several possible explanations for how this might occur. It's not that our obese friends, siblings or spouses "talk us into" gaining weight. The authors propose instead that we become more comfortable with the idea of obesity by having someone who becomes obese in our inner circle to observe closely. We may begin adopting some of the behaviors that may lead to obesity, such as overeating or not exercising. In this way, obesity "spreads" throughout a social network.

In addition to the subject of this clinical trial, the way it was conducted is interesting.

Did the researchers decide to start studying obesity in these people over 30 years ago and then collect data on them, including who their close friends, siblings and spouses were, as well as what those friends, siblings and spouses weighed? No. Instead, they used data available from an ongoing study that is decades old. Known as the Framingham Study because it began with individuals who lived in Framingham, Massachusetts, the original purpose was to study heart conditions in a large, connected population. That clinical trial generated a huge database of information on the medical status and progress of thousands of individuals including, of course, their weight. But how did Drs. Christakis and Fowler get the information on the individuals’ friends, siblings and spouses? The Framingham Study asked participants for information on family members as well as for a contact person who was not family. That contact person was considered to be a close friend.

I find it fascinating that this timely, topical piece of research was made possible entirely with existing information from people who volunteered for a completely different clinical trial, years ago.

~Joe

Related Topics:

• WebMD Video: Healthy Eating - What to Put on Your Plate
• WebMD Video: How Fat Kills

Technorati Tags: obesity, friends, clinical trials, health and wellness

Risks and Benefits

Institutional Review Boards (IRBs) are responsible for determining whether or not a clinical trial may be conducted and under what conditions. Hospitals, clinics, academic medical centers and the institutions that host clinical trials all rely on their IRBs to carefully consider what is being proposed, including who the research participants will be. One of the most important considerations involves comparing the risks and benefits of the proposed research - also known as the "risk:benefit ratio."

While this may sound very exact and quantitative, typically no calculations are involved. Rather, several aspects of the proposed clinical trial are examined to compare the benefits and risks of each.

First, is the science solid enough to reasonably lead to an advance in our understanding of the biomedical phenomenon being studied? Is the protocol (the way the clinical trial is designed) logically constructed? That is, are the costs or risks of doing the research justified by an expected yield of significant new information?

Second, are the discomforts and risks to the research participants reasonable when compared with the likely benefits to the participants and to society at large? Time spent, uncomfortable clinical tests and obnoxious side effects all contribute to the overall risk. Individual participants may benefit from closer health monitoring and potential improvement of their medical condition. Knowledge about curing or preventing the clinical condition being studied is a potential benefit to society.

The risk:benefit ratio cannot be reliably predicted for the individual research participant, however. (If it could, there would be no reason to do the research.) In fact, for an individual, the side effects of a medication being tested may be so severe that the individual perceives her participation to present a very unfavorable risk:benefit ratio.

The role of the IRB is to make sure the clinical trial is designed in such a way that the overall benefits are worth the overall risks. And if they are not, then the IRB must disapprove the clinical trial.

As for the individual - she must decide for herself whether the benefits are worth the risks. And she often doesn't have enough information to do that until her participation in the clinical trial has finished.

-Joe

Related Topics:

• WebMD Video: Behind the Scenes of a Clinical Trial
• Fact or Fiction? Take the Clinical Trials Quiz

Technorati Tags: clinical trial, risk benefit ratio, institutional review board, IRB, health and wellness