With the steady flow of new drugs emerging each year from the pharmaceutical research pipeline, doctors can often choose from a variety of drugs to treat a given health problem. But with each new entry, doctors, patients and health plans must determine whether the new drug is any better than the drugs that preceded it.

Increasingly, when there's no definitive answer, it's money that decides the issue. Insurance companies are routinely limiting access to new drugs unless patients show that older, less expensive drugs aren't working for them.

Insurers argue that they're protecting against the risk of undiscovered problems with unproven drugs and being good stewards of limited health care resources. But doctors counter that health plans are interfering with their ability to practice medicine, and doing so for their own financial gain, while patients feel they are being denied access to potentially life-changing treatments.

A test case

The debate has boiled over in recent years among doctors treating patients with fibromyalgia, a systemic condition marked by chronic pain and a host of difficult-to-treat symptoms. Until recently, there were no drugs specifically tested and approved for the treatment of fibromyalgia. Instead, doctors used a variety of medications approved to treat things like depression, seizures, pain or muscle spasms, a practice known as off-label use.

Then in 2007, Pfizer's Lyrica became the first drug approved by the Food and Drug Administration specifically for the treatment of fibromyalgia. Doctors thought it would be their go-to medication for treating the condition, but insurers thought differently.

Many set up prior authorization conditions for the drug, requiring patients to try the seizure medication gabapentin or antidepressants such as amitriptyline first. If those generic drugs didn't work for the patient, then the insurer would pay for Lyrica.

Physicians were stunned that insurance companies would force them to prescribe a drug that wasn't even approved for fibromyalgia before they could use a drug that was.

“We know (Lyrica is) safe, we know what the side effects are and we know that for fibromyalgia, it's very effective,” said Dr. Cody Wasner, a Eugene rheumatologist and president of the Oregon Rheumatology Alliance. “And yet we are forced to do the opposite.”

When two more brand-name drugs, Cymbalta and Savella, were approved for fibromyalgia, insurers put in place the same preconditions. Patients had to fail with the generics before they could get the new drugs.

LifeWise Health Plan of Oregon, for example, requires fibromyalgia patients to fail on gabapentin and at least two other generics before approving Cymbalta. The insurer did not agree to an interview, but in an e-mail to The Bulletin said it uses the approach, known as step therapy, “to ensure that members are receiving clinically appropriate and cost-effective medications.” The LifeWise officials said they will approve a more expensive drug if a physician is already having success treating a patient with it. That can happen, for example, if a patient transfers from another plan or has paid for the drug himself during a test period.

Last year, the rheumatology group appealed to Regence Blue Cross Blue Shield, the largest insurer in Oregon, to stop the practice, but was rebuffed. Appeals to the state's insurance commission, the pharmacy board and even the Legislature all proved fruitless.

There still have been no head-to-head comparisons of the effectiveness of the older generics against the new brand-name drugs in treating fibromyalgia. But doctors say they've noticed fewer side effects with the newer drugs. It has put them in a difficult position of being unable to prescribe the drug they think will be the best choice for patients.

“The physician has an ethical dilemma, in that they have to say, ‘Am I going to give the patients side effects to satisfy the insurance company, so they can be able to afford the drug that we think is more appropriate?'” Wasner said. “The insurance company is really practicing medicine without a license and by way of the pocketbook, interfering with the best care.”

Seeking relief

Patients often see the new drugs as the latest and greatest, spurred by the hope that they represent a new breakthrough that will finally relieve their long-standing pain. And pharmaceutical companies drive demand with direct-to-consumer advertising and patient education websites that tout their products. So when insurance companies require patients to try multiple generics first, it can seem like pointless hoops to jump through to get the drugs they want and their doctors recommend.

Patients and their advocates see little medical justification but plenty of economic reasons why the generics should be considered the drugs of choice.

“It's strictly financial,” said Rae Gleason, executive director of the National Fibromyalgia Association. “The thing about it that is so sad is that so many of these patients have been on these other medications already and know they don't work.”

Gleason said each of the three brand-name medications works for about 30 percent of fibromyalgia patients. A fourth drug, sodium oxybate, is awaiting FDA approval. In phase three trials, the most rigorous step in the testing process, the drug significantly reduced fibromyalgia pain in more than 50 percent of patients. That would represent a quantum leap over the old generics, but Gleason said she expects to see insurance companies put up the same roadblocks for patients if the new drug is approved.

“They absolutely will. It's horrible, but this one will be very expensive,” Gleason said.

Insurers, however, say the evidence is simply not that cut and dry when it comes to comparing the new products with the track record of the generics.

“We looked at the science of the nonapproved agents for fibromyalgia and the FDA-approved agents, and there wasn't a difference in the evidence across all the options,” said Helen Sherman, vice president and chief pharmacy officer for Regence.

Sherman said there was no evidence — as doctors had claimed — that there are fewer side effects with the newer brand-name drugs. Because these drugs are relatively new to the fibromyalgia market, insurers can't assume that adverse side effects won't become evident as more patients are prescribed the drugs.

“Early out of the gate, we just don't know what we don't know about a new medication,” she said. “Just because it hasn't been detected in a scientific study, there may be issues there that are undetected. We've seen so many examples of that.”

Sherman said step therapy is used for brand-name drugs that are likely to be expensive or prescribed in large volumes when comparative effectiveness research isn't available. As more patients take these drugs, their experiences will help to inform the decision-making process.

“The generic medications for fibromyalgia had decades of experience,” she said. “We want to at least see a couple of years experience for the new medications, if everything else was equal.”

Sherman said the company evaluates new drugs based on their relative value, taking into account effectiveness, side effects and price.

“Price is actually the tail end and the least weighed in,” she said. “If something is a lot more effective than the other options but costs more, we will embrace that product as a high-value choice.”

There have been many cases where newer brand-name drugs have proven no better or even worse than the older generics. Research funded by the Agency for Healthcare Research and Quality, for example, found that more expensive brand-name antibiotics were not as effective as some of the less expensive generic antibiotics for treating middle ear inflammation in young children.

Weighing the options

For the insurance companies, the difference comes down to paying anywhere from $75 to $150 a month for the three brand-name drugs now on the market versus approving a generic that often costs less than the patient's co-payment. But that still pales in comparison with many of the more expensive drugs that are routinely covered.

“None of these drugs is very expensive. They're all in the neighborhood of about $100 per month, said Kim Dupree Jones, an assistant professor of nursing and medicine at Oregon Health&Science University in Portland, and director of the Fibromyalgia Information Foundation. “In the rheumatology clinic, I'm used to dealing with drugs that are thousands of dollars a month. And the insurers don't blink at that.”

Jones said the issue is a problem due to the number of patients who have fibromyalgia, some 15 million in the U.S.

“So when they say you can have drug x or drug y, they're opening it up to a lot of people,” she said. “I think it's a numbers issue.”

Jones maintains it's a mistake to automatically rule out the generic drugs as options, simply because they are older. But while they are effective, they have major drawbacks, she said.

Some suffer what doctors call dose escalation, the need to constantly increase the dosage the longer a patient takes the drug. Others affect multiple receptors in the body, creating side effects such as dry mouth, dry eyes or constipation.

Choosing the right drug for patients, however, is difficult because doctors don't have good ways of differentiating between different fibromyalgia patients.

With breast cancer, Jones explained, doctors can test a biopsy sample of the cancer to determine which treatment will be most effective, in what dose and for how long. For fibromyalgia patients, none of that kind of subtyping exists.

“That's sort of the Holy Grail of fibromyalgia,” Jones said. “We're not there yet. It's somewhat trial and error, and it's somewhat ‘Which symptoms are driving the problem?' ”

Jones has her patients choose from a list of 37 common symptoms and then asks them to identify the three symptoms that have the biggest impact on their quality of life. Those symptoms can then help her guide her choice of generic or brand-name drug. For example, if patients also have symptoms of depression, doctors can prescribe Cymbalta, which is also an antidepressant.

While Jones isn't opposed to using the older generics, she doesn't particularly like the step therapy approach because it can create additional hurdles for patient and doctor.

“By the time they get to the rheumatologist, they've been dealing with this for six to 10 years, they've tried everything out there,” she said.

“It's just not a good use of our time to continue to go back and dig up documentation about where they failed.”

Limited gains

Alison Suran, a physical therapist with Healing Bridge Physical Therapy in Bend, sees many fibromyalgia patients struggling with their condition. And the additional burden of trying to get insurance approval for their medications just adds to their stress, she said.

“They have often already gone through a lot of medication trials to try to come up with something that works. And when they do find something that is helpful, they want to stick with it.” Suran said.

“So when an insurance company decides they won't cover that prescription until they've documented trying other things, it can be a big setback both physically and emotionally.”

Patients with chronic pain have incredibly sensitive systems, and even small changes can wreak havoc on their ability to control their pain.

“These folks are already struggling more than most of us can imagine with daily pain,” Suran said, “Having to deal with the unpredictable (nature) and inconsistencies of insurance coverage adds to their stress, which can add to their pain experience.”

Several analyses suggest that using prior authorization might not save that much money in the long run. A recent article in the American Journal of Managed Care calculated that after accounting for the price of alternative drugs, the costs of dealing with prior authorization requests, and the percentage of patients who will fail on generics and end up on brand-name drugs anyway, prior authorizations for Lyrica provide only minimal savings for insurers. The analysis, however, was funded by Pfizer, the company that makes Lyrica.

In other states, fibromyalgia patients have started grassroots campaigns to outlaw the practice of mandating failure on one drug to get access to another. California lawmakers passed a law earlier this year limiting health plans' ability to create step therapy requirements. The Missouri Legislature also took up the issue after a lawmaker's mother faced a seven-step approval process to get a brand-name fibromyalgia drug.

Dr. Dan Fohrman, a Bend rheumatologist, has been involved in the fight to remove preconditions for brand-name fibromyalgia drugs in Oregon. But he sees the issue as much broader than simply an issue over access to drugs for a single group of patients.

“Fibromyalgia is an unfortunate poster child for the balance of what happens with insurance companies and how out of control they are,” he said. “Nobody is willing to regulate them, they do whatever they want, and they intercede in physician-patient relationships.”

He's seen insurance companies flip their positions on covering rheumatoid arthritis drugs after prices dropped on one of them, and worries the fibromyalgia case might be repeated with new drugs for lupus now working their way through the approval process.

“It's their way of dealing with people and problems in medicine,” Fohrman said. “They use data to manipulate things for their own economic benefit.”