PHCentral: "Dr. Rubin, we are considering creating a forum for UT-15 patients. However, we are sensitive to the ongoing UT-15 trials and do not wish to compromise their validity. Therefore, we are requesting your thoughts or concerns about this forum. If you would prefer that we not establish this forum until the study has been closed, we would appreciate a brief paragraph expressing your concerns as well as your permission to present your concerns to the users of our website."

Dr. Rubin (Lewis J. Rubin, M.D., Professor of Medicine; Director, Division of Pulmonary/Critical Care Medicine, UCSD Medical Center): "...I would strongly suggest against creating a forum specifically for the UT-15 patients: although I think it is very important and helpful for patients and their families to have a forum to communicate, I think interactions during an ongoing study can lead to much confusion, comparison of treatments or treatment regimens which may be inappropriate, and inaccurate information- all of which could lead to compromising the study. I would strongly suggest that a forum not be initiated until the study has been closed which will only be several months from now. Since many new protocols are also being developed to study other drugs including several oral or inhaled agents, I believe that this policy should be carried forward for the future."

PHCentral: "Dr. Oudiz, as you may know, we've been asked by numerous patients to open a discussion "forum" on the topic of UT-15. We may do so, but we would have to actively monitor the messages to see that studies were not corrupted by the conversations. That's a tall order, and for the time being we've simply posted a message that essentially says that we're taking the matter under advisement. I think that if we had an article that explained the concepts of "blinding" (single/double/triple), placebo effects, clinical trials, FDA approval, and so on, it would help all our readers understand the science behind medical experimentation. The understanding would hopefully lower patient frustration and improve adherence of experimental subjects to study protocols."

Dr. Oudiz: The purpose of the placebo-controlled drug trial is to insure that no bias affects the outcome of the drug trial. In general terms, it is important that a patient taking an experimental drug experience an effect that is due solely to the drug, and not the so-called "placebo effect." The placebo effect can trick the patient into thinking he/she is deriving benefit or harm from a drug when in effect this benefit or harm is actually due to psychosomatic or incidental causes .

Studies of new or even established drugs have much more powerful conclusions when conducted using a placebo arm. These include studies of psychiatric drugs, drugs for heart and lung disease, and even trials in which vitamins are used. In studies where a placebo arm was not used, it is extremely difficult to determine if an outcome was due to equal effectiveness of drug vs no drug, or was the result of a Type II error; i.e., erroneously concluding that there was a difference when, in fact, no difference between drug and no drug existed (or vice-versa).

In conducting a placebo-controlled trial, it is imperative that the participants, doctors, nurses, and patients alike maintain a neutral bias with regard to whether or not a patient is receiving a placebo. It is important, therefore that any discussion about the likelihood of receiving placebo or real drug does not take place during the part of the trial in which the placebo is given. This includes patient-to-doctor, patient-to-nurse, and patient-to-patient conversations. With the recent widespread use of Internet chat rooms and bulletin boards, it is especially important that patients participating in placebo-controlled trials do not discuss details of the trial with others such as whether or not they think they are on a placebo.

Participants in placebo-controlled trials are cautioned in discussing details of their trial before unblinding from placebo, as it may adversely affect the outcome of the approval process by the Food and Drug Administration. In addition, even after unblinding from placebo, a patient discussing details of their trial with another patient that might still be blinded themselves could violate the study protocol. Thus, a drug that would otherwise be promising for use in the treatment of a particular disease might not be approved for use if there is a suspicion that the placebo arm of the trial was violated.

All biomedical research should adopt the standards of the Declaration of Helsinki, a copy of which can be found by clicking on the following link:

http://www.rcjournal.com/author_guide/helsinki.asp

Editor's note: The response given by Dr. Oudiz can also be found on his Center's Website along with other useful information.
The Liu Center for the Study and Treatment of Pulmonary Hypertension

Patient - Lisa Wright: I think the [doctors' comments] are very helpful. One of them did bring one question to mind, however. I'm well aware of what I'm not supposed to talk about during the initial twelve-week blinded portion of the study. Dr. Oudiz's [article] stated that a forum could also create a problem by intermingling people who were finished with the blind portion with people who were still in the blind portion. Does this mean that, once the initial twelve weeks are over, two people who are both definitely on the medication (past the first twelve weeks) can privately discuss the side effects, best medications for side effects, how they're doing, etc.?