Chantix News

VA Leaders Questioned On Response To Suicide Risk In Agency Study

-US Medicine

07/30/2008- WASHINGTON—In what is becoming a regular ritual on Capitol Hill, legislators took Department of Veterans Affairs (VA) leaders to task last month, this time for a possible breakdown in the agency’s human subject protection system of a study on combining smoking cessation therapy with therapy for post-traumatic stress disorder (PTSD). The study began in 2004 and was designed to determine whether smoking cessation therapy would be better implemented when combined with PTSD therapy, or whether treatments should be kept separate. Irregularities came to light in June in news reports that highlighted the discovery of suicide as being a possible side effect of Chantix, one of the smoking cessation drugs administered to some patients in the study, and VA’s delayed notification of study participants taking the drug of those side effects.

The study, called "PTSD and Smoking Cessation Study #519," was designed as a five-year study on health services delivery. Veterans enrolled in the study suffered from PTSD, as well as a smoking addiction that they wanted to kick. Treatment was varied and depended on the patient and what their individual care provider recommended. Of the 945 veterans in the study, 241 were at one point in time prescribed Chantix—considered the most effective anti-smoking pharmaceutical and used by more than 5 million people in the United States. Of the 241 patients prescribed Chantix, 75 had a total of 114 adverse events; 19 of those 75 had psychiatric adverse events, including 11 patients who had 12 episodes of suicidal ideation. There was one suicide attempt in that group, and no suicide completions.

However, the study has not been curtailed or modified in light of the controversy, and is still underway.

In November, 2007, the Food and Drug Administration (FDA) released an early notification to the public that it was looking into accounts of suicide linked to the use of Chantix. In early February, 2008, FDA released a report verifying those links, adding an increased chance of suicide to Chantix’s list of possible side effects. Near the end of February, VA directed the various sites involved in the study—11 sites throughout the VA system—to send a notification to patients in the study taking Chantix of the FDA’s findings. Some patients received the notification soon after the VA’s decision. Others did not receive any word until June, when the study first made headlines.

At a House VA committee hearing on July 9, titled "Why Does the VA Continue to Give a Suicide-Inducing Drug to Veterans with PTSD?," legislators probed into the study’s validity, its safety, whether Chantix should continue to be on the VA formulary, and questioned whether VA needed to take a serious look at the systems in place to keep its study subjects safe.

One Participant’s Experience
Testifying before the committee was retired Spc. James Elliot, a former Army sharpshooter, who served a 15-month tour of duty in Iraq in 2003-2004, and whose story, reported originally in the Washington Times, ignited the controversy surrounding the study. Three years ago, Elliot was diagnosed with PTSD and has since received care through the VA health care system. He also had a two pack-a-day smoking habit. He enrolled in Study #519 and began receiving smoking cessation therapy last year under the care of his psychiatrist at the Washington, D.C., VA Medical Center (VAMC).

"I began with the nicotine patch (21 mg per day) and that did not work very well," Elliot explained. "It did not completely eliminate my smoking habit. From there I went to nicotine gum. At one point I was given both in conjunction with one another."

In October, 2007, Elliot was given a prescription for Chantix, and began the course of treatment on November 5.

Chantix cut Elliot’s smoking habit in half overnight, he said. However, a week later, he began experiencing hives and uncontrolled itching. During an appointment with his primary care physician—one other than the VA psychiatrist who prescribed the drug—Elliot was advised to quit taking the medication. But a month later, in December, his VA psychiatrist recommended that he go back on it, this time at a reduced dose, and so he began taking Chantix again.

In the meantime, his behavior began to become erratic. Couples counseling sessions with his fiancée conducted at a Vet Center near his home in Silver Spring, Md., were unsuccessful because he was not stable enough during the sessions to participate. In mid-January, feeling that he was headed for a psychological breakdown, Elliot attempted to see his VA psychiatrist, requesting emergency treatment, but was turned away by the receptionist after taking his information.

On February 5 of this year, four days after the FDA released its safety advisory on Chantix, Elliot’s behavior became so erratic and volatile that his fiancée attempted to take away his car keys. When he would not let her, she called the Montgomery County Police, who, when finding Elliot in the street outside his house and in possession of a handgun, tazered him after a 20-minute stand-off.

"I strongly feel that the drug (Chantix) led to that episode," Elliot stated. "When I reached out [to VA] that one time, and that was the most important time, I had the door slammed in my face."

He added, "Human testing at the VA should be eliminated."

Defending The Process, Condemning The Execution
VA officials have continued to defend the timing of when the department directed that study participants be notified of the FDA’s advisory. VA Secretary Dr. James Peake testified at last month’s hearing that, although the intent was right, the execution encountered problems.

"On the 20th of November [in 2007], the early communication [from FDA] came out. In fact the very next day, we notified the clinicians through our pharmacy benefits channel. There was not felt to be, and I believe very appropriately so, on the basis of that early communication, a reason to go out and contact every patient that was on [Chantix]. I think that was an appropriate judgment at the time," Dr. Peake explained. "On February 1, [2008] when the public health advisory came out from the FDA—we took that more seriously in terms of a call to action. Immediately that was passed through both research channels and to clinical channels to those that prescribe Chantix and have patients on Chantix. In mid-month, the research community that was responsible for the study got together and had a discussion about it and decided that we should notify our patients. That’s when [a letter describing Chantix’s side effects] was put together and the addendum was put together for the consent. That was sent to each of the [independent review boards (IRBs) of the VA medical centers participating in the study]."

Some facilities, Dr. Peake said, sent the letter out near the end of February.

"[It was] a one-month delay, which might be considered an appropriate deliberation period," Dr. Peake contended. "Others did not send it out until June, which to me—I’m not sure I understand why."

Dr. Peake admitted that having separate IRBs at each facility responsible for the notification led to the delay and that there is likely a more efficient, manageable method.

"We’re already starting to form a central IRB so that we can have better and tighter execution in a study like this, so they have a common standard, and you have a way to hold people accountable and get the word out," Dr. Peake said.

A standard method is needed, he admitted, on how to notify patients in cases such as this.

However, he said, there is no existing evidence to justify pulling Chantix from the VA formulary, and that to call Study #529 a "drug study" is a misnomer.

"The modalities we are using are proven modalities for stopping smoking. The question that needs to be answered, which you can’t answer in the short-term, is is it better to do it with PTSD treatment, or to do your PTSD treatment separately from the smoking cessation environment," Dr. Peake explained.

What Dr. Peake found most disturbing was Elliot’s description of being turned away by a VA mental health office in January when he came seeking care and fearing he was heading for a mental and emotional collapse.

"I had not heard his emergency problem and not having care, until he testified here today," Dr. Peake said. "That’s something we need to drive down and make sure what really happened and make sure it never happens again."

Investigations Underway
Two separate investigations on the study are currently underway—one by the VA Office of the Inspector General (OIG) and one by the VA Office of Research Oversight (ORO)—reviewing the protocols of Study #519.

Thomas Puglisi, PhD, ORO chief officer, testified that he had serious concerns over how safety protocols were followed in the study.

"I have concerns on the level of this particular study, and I have concerns system-wide," Dr. Puglisi said. "In terms of this particular study, I’m concerned that it appears that at least some veterans who were prescribed Chantix never received written information about Chantix. I’m concerned that at some of the study sites, there appears to be an undue delay in getting information to study participants. I’m concerned on a systemic level that we apparently don’t have the mechanisms to make sure these things are done in a timely fashion. I’m concerned any time informed consent appears not to have been adequate. That is one of the keystones of human subject protections. The [VA] Secretary has asked my office to look at this study in great detail, as well as all studies involving PTSD patients."

Dr. John Daigh, VA’s assistant inspector general for health care inspections, testified that the OIG’s investigation—mainly limited to the Washington, D.C., VAMC where Elliot was being treated, found little problem with the VA system, but rather problems in regards to how employees deviated from that system.

"We do not interpret at all that there are dramatic deviations from human subject protections in this study in that you had to sign consent in order to determine whether or not you were a reasonable candidate for this study and you had to sign another consent to be a part of this study. Our problem is that the study began and, over time, knowledge changed about the therapies for Chantix," Dr. Daigh explained. "When it became clear with the February warning that there was a significant risk, the IRB locally at the D.C.VAMC made the judgment that patients would be notified, but the execution of that plan failed."

While the VAMC sent letters to patients in the study taking Chantix, there was no reliable way of determining how many of the veterans actually received the notification. The OIG further determined that the letters did not adequately explain the risks associated with the drug.

"I would also comment that in our work we looked at both the care provided on a clinical nature—to those patients that were [taking Chantix] that were not part of the study, and those that were part of the study," Dr. Daigh noted. "I would have to say that the pharmaceutical staff reacted aggressively in taking the names of individual patients to the clinical leaders in the hospital, so they were aware of the patients under their charge that were on this drug. We found that the reaction on the clinical side [as opposed to the research side] was effective."

Neither investigations are looking at the safety of Chantix in PTSD patients. Pfizer, the maker of Chantix, is currently undertaking further studies on the drug’s effects on patients with schizophrenia and other mental illnesses, however, those will not be complete for several years.

Rep. Bob Filner (D., Calif.), chairman of the House VA committee, suggested, though, that Dr. Peake might want to consider pulling Chantix from the VA study and seeking alternative smoking cessation therapies for all VA patients with PTSD looking to quit smoking.

"Prudence says that for these individuals who have PTSD—they have enough problems. Don’t aggravate it. They’ll use other things to stop the smoking," Rep. Filner told Dr. Peake. "I can’t believe that you all have 100 per cent confidence that we’re not having suicides [caused by taking Chantix]."

Rep. Filner’s insistence on focusing on the drug rather than the study’s human subject protections caused some disagreement among other committee members.

"Calling a drug, Chantix, a suicide-inducing drug, is very misleading. What we should focus on is the [human study protection] and whether the rules have been followed by VA," declared Rep. Steve Buyer (R., Ind.), ranking Republican on the committee. "With the possible exceptions of doctors [Rep. John] Bozman [R., Ariz.] and [Rep. Vic] Snyder [D., Ariz.] (the two committee members with medical degrees), I doubt anyone on this committee has the expertise about what drug should be administered by VA and what drugs should be on the formulary."

Rep. Snyder agreed, and expressed disappointment that the committee should in any way pressure VA to deny Chantix to veterans seeking to stop smoking.

"I think we do a disservice to anyone with PTSD if we say that you have lost all your faculties and judgment to sit down with your doctor and decide what’s the best treatment for you," Rep. Snyder said. "My Dad had PTSD. He was a WWII vet; he was one of Patton’s folks and he got involved in burial detail of guys who got burned and killed in tanks. It was terrible. And to the day he died, he did not watch anything on TV except for variety shows and game shows. No cowboys and Indians, no wars, no crime. He didn’t want anything that smacked of violence. He didn’t know he had PTSD; he never talked about PTSD. He died of his smoking. He went in to have surgery and couldn’t get off the ventilator and he died. I don’t think he was suicidal. I think if he had any inclination at all of what smoking had done to him, and we know more now, he would have gladly sat down with a practitioner and said—you mean if I take that little pill, I can get rid of this habit that’s going to kill me? I would hate the signal that the folks that have anxiety or bipolar disease or depression or PTSD that the studies aren’t out there yet, so keep smoking. I think that would be a terrible, terrible disservice."

Rep. Snyder expressed concern that, due to this incident, the idea of research being performed by VA might fall into disfavor.

"One of the unfortunate things that was said today was somehow implying that research at the VA was a bad thing and somehow should be eliminated. That would be a tragedy. Never in my history have I heard that view expressed before, and it would just be heartbreaking that the take home should be that we shouldn’t be doing research in the VA system," Rep. Snyder declared. "This is the kind of study that doesn’t get funded over the long-term very much. Why is that? Because there’s not money to be made in this study. This is about delivery of products that are already on the market. I’m a family doctor and we talk about that. We need more primary care research, because you’re talking about where the best place to do the treatment is."

"This country needs more of this kind of research," he noted. "At the end of the game, you’re not going to say, ‘It’s best that [smoking cessation] it’s done in a PTSD clinic,’ and somebody can go patent that and make a lot of money. There’s not that kind of incentive here. It’s about delivery of health care, and in fact, the VA system might be one of the few systems that will be able to do that, because nobody else will have the money to do that kind of research."