In early January, the FDA approved Abstral (ProStrakan), a transmucosal fentanyl tablet indicated for breakthrough cancer pain. Not surprisingly, Abstral was approved with a Risk Evaluation and Mitigation Strategy (REMS); however, Abstral’s approved program was slightly different from other approved REMS, even those for fentanyl products indicated for breakthrough cancer pain or powerful opioids like oxycodone: It included a patient–prescriber agreement that physicians would have to use for every patient for whom they prescribed the drug.

Patient–prescriber agreements—alternately called opioid contracts or opioid agreements—had been long discussed at the FDA. As early as 2009, the agency suggested these agreements might be part of the REMS program. However, a number of concerns were raised, both in online comments submitted to the agency and in FDA public hearings on the program. In June 2010, when the FDA released its guidance to industry on developing REMS, the agency specifically stated that the “FDA is not proposing to require pain treatment agreements or patient/provider agreements under the REMS.” However, the guidance document did emphasize that the FDA wanted to make patient–prescriber agreements more widely available to opioid-prescribing physicians.

Abstral’s approved REMS program clearly took a different form. Near the bottom of the patient portion it states, “I understand that I am not required to sign this Authorization. However, if I do not sign, I will not be able to enroll in the Abstral REMS program and will not be able to receive Abstral.”

Although they have now become ubiquitous, requiring patients to sign an opioid agreement—at the risk for forgoing treatmentraises questions about the ethics of the agreements and whether their relative value outweighs the effect they have on the doctor–patient relationship.

At What Cost and for What Benefit?

Last April, the American Journal of Bioethics convened a panel of multidisciplinary experts to weigh in on the pros and cons of opioid agreements. Although the panel’s report emphasized doctor–patient communication of the risks and benefits of opioid therapy, these experts also outlined a number of unintended consequences associated with their use; among them were the following: stigmatizing pain patients; creating barriers to opioid prescribing; undermining physician–patient trust; contributing to the “legalization” of medicine; and eroding the ethical responsibility of physicians to put the patients’ needs above their own—in this case, the “chilling effect” of increased regulation by state medical boards and the U.S. Drug Enforcement Administration.

Despite their popularity, it is generally accepted that there is scant evidence that opioid agreements alone minimize risk when prescribing opioids.

In a literature review of opioid agreements used in the treatment of chronic noncancer pain published in 2010, Joanna Starrels, MD, assistant professor of medicine at Albert Einstein College of Medicine in New York City, found only four studies that compared outcomes of patients with and without opioid agreements. All were retrospective and observational and “importantly, none of the studies evaluated the outcomes that are most clinically important, such as addiction and overdose,” Dr. Starrels said. “These [agreements] are being rolled out by physicians every day … but we don’t know what the benefits—or the risks—are.”

“There is this perception that there is something legal and binding about this; therefore, this agreement changes behavior. There is no evidence that we know about that it changes behavior,” said Bill McCarberg, MD, founder of the Chronic Pain Management Program for Kaiser Permanente in San Diego, and a Pain Medicine News editorial board member.

One of the major ethical concerns with opioid agreements or contracts is that they presume patients are equal partners in a patient-centered approach; however, in reality, patients have no choice but to sign them if they want treatment.

“The crux, the underlying problem, is that there is a tremendous power differential between a patient who wants something that only the doctor can give,” said Dr. McCarberg. “An [opioid] agreement is inherently unequal so that the patient, in my estimation, always agrees to sign a contract.”

The act of signing is key. Physicians often feel it’s necessary because unlike prescribing insulin for diabetes, for example, a noncompliant pain patient on opioid therapy can be a significant medicolegal liability for a prescribing physician.

From patients’ point of view, it can cultivate a sense of mistrust and shame.

“We don’t make contracts for anything else, so it makes patients feel like they are not respected or not trusted, or like they’re doing something wrong, when all they are trying to do is get their pain treated,” said Robert Arnold, MD, chief of the Section of Palliative Care and Medical Ethics at the University of Pittsburgh Medical Center.

“It’s universal, when somebody asks me to sign something, my back immediately straightens up,” said Will Rowe, CEO of the American Pain Foundation, a patient advocacy group. “I get suspicious, I get cautious, I start to doubt and I wonder what is going on here.”

As opioid agreements become increasingly more common—indeed at the point that they are federally mandated before prescribing certain drugs—their significance may become diluted. For example, the Abstral patient–prescriber agreement must be countersigned by both patient and provider and faxed to the Abstral REMS program within 10 days. If it is not received, the patient’s prescription is blocked. Furthermore, the patient portion includes 12 points outlined in legalese; if the document is an agreement in letter, it is certainly more of a formal contract in spirit.

Although the motive behind opioid agreements may be a good one, they risk becoming another bureaucratic hurdle for physicians to jump through and yet one more document for a patient to initial while sitting in the waiting room.

“If the emphasis is on getting a piece of paper signed, one that people sign but may or may not read, may or may not understand, then to me it’s hurting the process, rather than helping it,” said Steve Passik, PhD, a psychologist who specializes in palliative care and pain management at Memorial Sloan-Kettering Cancer Center in New York City, and a member of the Pain Medicine News editorial board. Expectations from both the patient and the physician about what constitutes appropriate use of opioids should be an ongoing, living dialogue, he added.

An Ethical Morass

Some agreements go a step beyond inconvenience, to the point of being impractical or immoral. Dr. McCarberg mentioned that he has seen opioid agreements demanding concurrent treatments like physical therapy that were impossible for some patients to perform.

And yet one step further, some agreements are literally ultimatums, which physicians use as grounds for “firing” noncompliant patients. Unanimously, physicians interviewed for this story said this was a breach of medical ethics, particularly among pain specialists.

When a specialist “fires” a patient, “all you are doing is then sending them back to their primary care doctor, who sent them to you because they didn’t know what to do,” said Dr. Arnold.

Moreover, the physician probably isn’t helping the patient by denying treatment. “It’s never been shown that firing someone from pain management necessarily helps their substance abuse problem,” said Dr. Passik. “And there are a lot of ways that I can think of that it can get worse.” Barred from medical treatment, these patients may turn to street drugs for relief.

Provided there is no drug diversion taking place, substance abuse and dependence is a treatable, psychiatric condition that should remain private between the treatment team and the patient, Dr. Passik said. “Why lose the leverage we have when offering help with pain to also try to help the person with an addiction?” he asked.

A Chance for an Open Dialogue

Regardless of their flimsy evidence, or the ethical complexities, it would seem that opioid agreements are here to stay. What, then, makes a good one?

Ultimately, the agreement itself is somewhat beside the point, experts say, although the language and tone clearly are important on one level.

What is more important—regardless of whether anything gets signed, faxed and filed away—is a thorough and open dialogue about why opioids are different from other medicines. A good agreement, whether it’s drafted by the physician or downloaded from the Internet, should simply serve to open an ongoing dialogue about the risks of opioids and what the patient and physician can expect from each other.

“One of the major questions about using treatment agreements is what they should look like,” said Dr. Starrels. “It’s clear that we should be discussing the risks and benefits of opioids with all of our patients, and it’s clear that we should tell them … what they can expect when entering a treatment plan with a provider. The question is, what form this communication should take, and is a written document the best way to go?”

Although there is little evidence for opioid agreements per se, Dr. Passik points to studies of patients with opioid addiction. In one recent study of pain patients on methadone in a highly structured program of medication adherence, patients’ alliance with their therapist was the best predictor of outcomes (J Subst Abuse Treat 2008; 35: 174-183).

“What pain practitioners have to ask themselves is, ‘I’m doing all of these [risk management maneuvers], but is it hurting or helping my communication and the working alliance that I’m building with my patients?’” said Dr. Passik. “Because that is the best predictor of how we are going to do.”