Trial and error: Doctors testing devices and drugs

David Gulliver
http://www.heraldtribune.com

A pulmonologist snaked a tube through the nose and into a man’s lungs.

A nurse inserted a needle into a man’s arm and started an intravenous drip of a medicine.

A otolaryngologist made a small incision in the fold behind the ear of a man with persistent hearing problems, the first step in a delicate surgery.

The procedures, all performed in mid-May, were hardly unusual among the thousands performed across Southwest Florida.

But in these three, each patient turned to an experimental device or drug in hopes of finding a cure to conditions that threaten their lives.

About 32,000 such clinical trials are under way in the United States today, conducted by universities, private companies and the federal government.

Almost 6,000 have some Florida presence, such as a hospital or doctor recruiting patients. While most trial sponsors focus on larger cities — nearly 3,000 are in and around Miami — more than 500 sites are in Sarasota and Bradenton alone.

Most are single doctors or practices recruited to work on one study, often by drug manufacturers who already know the physician via his prescribing of its approved medications.

The studies can be profitable. The physician practice Bradenton Neurology spun off its clinical trials work into Bradenton Research Center, a self-supporting research arm with six employees. The private business does not disclose its finances.

Sarasota Memorial Hospital‘s Clinical Research Center had about 35 trials running last fiscal year, bringing in $580,724 but losing money on expenses of $804,131.

But it brings potentially groundbreaking treatments, normally the province of teaching institutions, to a community hospital.

SMH: hotbed for trials

SMH, the region’s largest hospital, is the local hotbed for trials. The hospital has been involved with clinical trials since 1989.

Its Clinical Research Center grew from pharmacy directors’ interest in new medications. Today, the center focuses more on medical devices — trials that depend on its capacity for complex surgeries.

Among the 19 active trials is one for treating emphysema — a special interest of the center’s new medical director.

Dr. Kirk Voelker, a pulmonologist and smoking cessation expert, took over this spring.

He has been involved with about 30 clinical trials during his career, including early efforts to fight emphysema with surgery to reduce lung volume.

The procedure seems counterintuitive — emphysema patients are short of breath.

But the problem is exhaling, not inhaling. The disease erodes the tiny air pockets in sections of the lungs, trapping air inside and making it difficult to take in fresh air.

Lung volume reduction works by taking away the ruined sections of the organ, so the remainder can work more efficiently. But it has a downside: It is a physically grueling surgery for patients in poor health.

Three trials at Sarasota Memorial offer solutions.

One is for a device called EASE, an acronym for exhale airway stents for emphysema. The doctor makes small openings between damaged lung tissue and air pathways, then inserts the stent — a small, wire-mesh tube — to keep that passage open, allowing trapped air to escape.

Two other trials at Sarasota Memorial — one complete, one soon to begin — are based on the same principle but different methods: One uses one-way valves, the other a sort of glue, to shunt air from damaged to healthy areas.

Among the center’s other trials are drugs for treating ovarian, breast and colon cancers, and techniques for heart bypass, stroke and aortic valve surgery.

Sarasota Memorial officials say it is one of just a handful of community hospitals with a dedicated clinical research center. Voelker attributes that to the doctors.

“We have a lot of motivated physicians who had excellent backgrounds in training or research before they came here,” he said.

Some of them are high profile enough that medical companies approach them directly. Most contacts, though, come directly to the center.

Voelker decides which studies the hospital will participate in. That entails working with the center’s seven-person staff, mostly research nurses who follow various branches of medicine. He also consults with doctors working in the study’s area.

But for the native Sarasotan, the decision starts with one question: “The first thing I ask is what kind of good can come out of this for the people of Sarasota.”

Who is it going to help?

That issue of potential benefit is at the heart of clinical trials.

By their nature clinical trials involve uncertainties spelled out in documents called informed consent papers, given to potential participants.

For example, the drug may not work, and even if it does, you may instead receive a placebo, an inert fake, so researchers see what difference the real medicine can make.

Dr. W. Alvin McElveen of Bradenton Neurology is always conscious of the ethical dilemma.

Since 1994 he has been working with drug companies, testing treatments for Alzheimer’s disease, epilepsy and other neurologic problems.

He has passed up on some studies that would have required patients to forgo existing, effective medicines to test experimental drugs.

“I have a hard time telling somebody that one, there’s a chance you won’t even get any drug, and two, there’s a chance that the drug I’m going to give you doesn’t work, whereas if you weren’t in the study there are all these other drugs I could offer you,” McElveen said.

So he is pleased to be part of the testing of a compound known as MBP8298, the creation of Canadian biotechnology company BioMS Medical.

The drug is for treating secondary progressive multiple sclerosis, the most debilitating form of the disease, which attacks the nervous system and can result in paralysis.

Though it is a double-blind trial, meaning some patients receive a placebo, it meets McElveen’s standards.

A smaller, earlier phase of the trial showed effectiveness in slowing the disease’s progression. So far, only one other drug has been effective on this stage of the disease, and it has significant side effects.

That previous trial’s success drew the attention of pharmaceutical giant Eli Lilly and Co., which last year struck a deal with MBP8298’s creator, BioMS Medical, potentially worth $410 million.

A larger trial is now running at 62 sites, including Bradenton Research Center, the affiliate of McElveen’s practice. He and his partners spun off the center five years ago.

“We got to doing so many patients that we had no room in the Bradenton Neurology office to see patients and do the drug studies,” he said.

Its track record includes a client roster that reads like the stock listings: Pfizer, Merck, GlaxoSmithKline, Novartis and Bayer.

What draws those clients is the doctors’ neurology practice, Manatee County’s largest. With more than 30,000 patients in its electronic medical record system, McElveen and his partners can quickly search for and identify potential candidates for a treatment.

About 60 patients are enrolled in the 15 active studies running at Bradenton Research.

All have to meet specific criteria. For McElveen’s multiple sclerosis study, for example, patients have to test positive for one of two immune response genes.

Among the 10 medical criteria for Voelker’s EASE study are various measures of breathing ability, and a requirement that patients quit smoking at least eight weeks previously.

The initial medical screening weeds out three-quarters of potential participants, Voelker said. The final comprehensive exam cuts four out of five of those remaining.

Participants also review detailed papers, known as informed consent documents, that spell out the risks and benefits of the study. That, too, can winnow the pool, Voelker said.

Participants generally are compensated only for time and travel expenses, but in some studies can receive small stipends.

They generally receive all related medical care for free, such as surgery, the medical device and any follow-up care or testing.

For some patients, the chance at an elusive cure is the motivation.

Free treatment

Dr. Jack Wazen’s patient had undergone multiple operations in hopes of improving his hearing, but with no success.

At the Cape Surgery Center last week, Wazen implanted a hearing device under the skin behind the patient’s ear. He then ran its slender wire through the mastoid bone and into his middle ear.

The procedure was part of an FDA-approved study on 25 patients of the feasibility of a new surgical technique.

The device, from manufacturer MED-EL and already approved by regulators, is for hearing loss caused by problems in the mechanics of the middle ear.

Wazen, part of the Silverstein Institute, also is recruiting patients for a trial of a device by the manufacturer Otologics. That device counters nerve-related hearing loss common among older people.

He also was part of a study last year for a tinnitus-countering device that required patients to pay some exam fees.

During the design of the Otologics study, the Silverstein Institute encouraged the company to cover more costs. Participants now will get the device and treatment for free.

He sees the trials as a chance to link patients to solutions when they might have given up, like his MED-EL patient.

“We find him to be a great candidate for the technology and hopefully this will do the trick,” Wazen said.

That sort of hope put Barbara, a 50ish woman with emphysema and a wild spray of red hair, into a machine the size of a phone booth and nicknamed the “body box.”

Its medical name is a plethysmograph, a device for measuring the volume of the lungs. Barbara, who asked to go only by her first name for this story, had driven from Melbourne for a shot at the EASE trial.

She had already reviewed the informed consent forms, and said she knew that even if she qualified, she might not receive the stent device.

“There’s a risk you take, but there’s a risk in daily life,” she said. “When you’re in a situation like mine, you go the extra little bit to improve your quality of life.”

At the device’s computer readout was Dayle Waltrip, a pulmonology function technologist.

She tells Barbara to insert the machine’s breathing tube — akin to a scuba mouthpiece — into her mouth. To get accurate results, she next has to play cheerleader.

“Deep breath now,” she tells Barbara. “Pull-pull-pull-pull, hold your breath now.” She counts down from five. “Push it out, keep going, keep going, keep going, keep going, keep going, keep going, you got it.”

Then there is a brief rest between tests, a three-hour drive home in the first downpour of the season, and the wait for a call.

see original