ICOO2015

BOSTON – Opioid abuse might be as much of a problem in patients with cancer pain as in those who need analgesia for another reason, according to palliative care physicians at the Dana Farber Cancer Institute who outlined their safeguards at the International Conference of Opioids.

“Let’s not lose sight of the fact that the very access to these medications, which can do so much good, is in jeopardy,” said Dr. Douglas E. Brandoff, a palliative-care attending physician at the cancer institute. In the current era of “unprecedented regulation and scrutiny,” Dr. Brandoff said, pain practices in cancer care must evolve “to keep up with the times.”

Evidence that opioid abuse among cancer patients rivals that of other patients prescribed those agents is limited but reasonably consistent, according to Dr. Brandoff. He cited several published studies, including a survey of hospices in which substance abuse and diversion were considered a problem in 38% (J. Palliat. Med. 2013;16:237-42) of patients.

“It’s a little disconcerting. This is hospice, right? This doesn’t happen in hospice, but unfortunately, it does,” Dr. Brandoff reported.

At the cancer institute, a multidisciplinary task force convened in 2013 has now produced numerous specific policies designed to protect patients and institutions from abuse of controlled pain medications. Those steps are not much different from those being increasingly employed in clinics for nonmalignant chronic pain, but they are applied uniformly in essentially every patient – not just those singled out for high risk.

One required step is the implementation of a prescription-monitoring program for every patient started on a narcotic drug in controlled substances schedule II or III, a benzodiazepine, or a department of public health scheduled IV or V controlled substance. Another is the use of a medication management agreement designed to educate patients about the benefits and risks of controlled substances and outline expectations. All patients and their clinicians are required to sign the agreement.

“If we have someone who is imminently dying within hours or days, then, no, I would not impose a management agreement expectation on them or myself,” said Dr. Brandoff, but he said that there are essentially no other exceptions.

The agreement, crafted with nonjudgmental language aimed at clarifying the goals of chronic pain relief, is entered into the medical record. It generally has been well accepted, according to Dr. Lida Nabati, also a palliative care attending physician at the cancer institute, Dr. Nabati, who participated with Dr. Brandoff in presenting the cancer institute’s safeguards, noted that patient resistance to the agreement often is a red flag for potential problems with abuse.

The movement to control opioid abuse in cancer patients is relatively new. At the time that the task force began, Dr. Nabati noted that few other institutions had formal policies in place even though others also were beginning to review their approach. As recently as 2014, a directive from the Department of Veterans Affairs for opioid therapy in chronic pain patients specifically excluded those with cancer, Dr. Nabati reported.

Yet, cancer “does not afford some magical protective effect” from the very same risk factors associated with opioid use in noncancer patients, such as anxiety, depression, or history of substance use, according to Dr. Brandoff. Rather, he suggested that the added stress of a cancer diagnosis could exacerbate those factors.

The implementation of strategies aimed at reducing the risk of opioid abuse in patients with chronic cancer pain is needed and timely, according to Dr. Mellar P. Davis, the co-chair of the 2015 ICOO meeting and director of the palliative medicine fellowship program, Taussig Cancer Institute, Cleveland Clinic.

In an interview, Dr. Davis applauded the types of strategies implemented at the cancer institute, which he believes protect the patient, the physician, and the institution. He believes that the patients might be the greatest beneficiaries when appropriate opioid use permits a gain in quality of life through effective but nondebilitating pain control.

Dr. Brandoff and Dr. Nabati reported having no financial disclosures.

BOSTON – Opioid abuse might be as much of a problem in patients with cancer pain as in those who need analgesia for another reason, according to palliative care physicians at the Dana Farber Cancer Institute who outlined their safeguards at the International Conference of Opioids.

“Let’s not lose sight of the fact that the very access to these medications, which can do so much good, is in jeopardy,” said Dr. Douglas E. Brandoff, a palliative-care attending physician at the cancer institute. In the current era of “unprecedented regulation and scrutiny,” Dr. Brandoff said, pain practices in cancer care must evolve “to keep up with the times.”

Evidence that opioid abuse among cancer patients rivals that of other patients prescribed those agents is limited but reasonably consistent, according to Dr. Brandoff. He cited several published studies, including a survey of hospices in which substance abuse and diversion were considered a problem in 38% (J. Palliat. Med. 2013;16:237-42) of patients.

“It’s a little disconcerting. This is hospice, right? This doesn’t happen in hospice, but unfortunately, it does,” Dr. Brandoff reported.

At the cancer institute, a multidisciplinary task force convened in 2013 has now produced numerous specific policies designed to protect patients and institutions from abuse of controlled pain medications. Those steps are not much different from those being increasingly employed in clinics for nonmalignant chronic pain, but they are applied uniformly in essentially every patient – not just those singled out for high risk.

One required step is the implementation of a prescription-monitoring program for every patient started on a narcotic drug in controlled substances schedule II or III, a benzodiazepine, or a department of public health scheduled IV or V controlled substance. Another is the use of a medication management agreement designed to educate patients about the benefits and risks of controlled substances and outline expectations. All patients and their clinicians are required to sign the agreement.

“If we have someone who is imminently dying within hours or days, then, no, I would not impose a management agreement expectation on them or myself,” said Dr. Brandoff, but he said that there are essentially no other exceptions.

The agreement, crafted with nonjudgmental language aimed at clarifying the goals of chronic pain relief, is entered into the medical record. It generally has been well accepted, according to Dr. Lida Nabati, also a palliative care attending physician at the cancer institute, Dr. Nabati, who participated with Dr. Brandoff in presenting the cancer institute’s safeguards, noted that patient resistance to the agreement often is a red flag for potential problems with abuse.

The movement to control opioid abuse in cancer patients is relatively new. At the time that the task force began, Dr. Nabati noted that few other institutions had formal policies in place even though others also were beginning to review their approach. As recently as 2014, a directive from the Department of Veterans Affairs for opioid therapy in chronic pain patients specifically excluded those with cancer, Dr. Nabati reported.

Yet, cancer “does not afford some magical protective effect” from the very same risk factors associated with opioid use in noncancer patients, such as anxiety, depression, or history of substance use, according to Dr. Brandoff. Rather, he suggested that the added stress of a cancer diagnosis could exacerbate those factors.

The implementation of strategies aimed at reducing the risk of opioid abuse in patients with chronic cancer pain is needed and timely, according to Dr. Mellar P. Davis, the co-chair of the 2015 ICOO meeting and director of the palliative medicine fellowship program, Taussig Cancer Institute, Cleveland Clinic.

In an interview, Dr. Davis applauded the types of strategies implemented at the cancer institute, which he believes protect the patient, the physician, and the institution. He believes that the patients might be the greatest beneficiaries when appropriate opioid use permits a gain in quality of life through effective but nondebilitating pain control.

Dr. Brandoff and Dr. Nabati reported having no financial disclosures.

BOSTON – Opioid abuse might be as much of a problem in patients with cancer pain as in those who need analgesia for another reason, according to palliative care physicians at the Dana Farber Cancer Institute who outlined their safeguards at the International Conference of Opioids.

“Let’s not lose sight of the fact that the very access to these medications, which can do so much good, is in jeopardy,” said Dr. Douglas E. Brandoff, a palliative-care attending physician at the cancer institute. In the current era of “unprecedented regulation and scrutiny,” Dr. Brandoff said, pain practices in cancer care must evolve “to keep up with the times.”

Evidence that opioid abuse among cancer patients rivals that of other patients prescribed those agents is limited but reasonably consistent, according to Dr. Brandoff. He cited several published studies, including a survey of hospices in which substance abuse and diversion were considered a problem in 38% (J. Palliat. Med. 2013;16:237-42) of patients.

“It’s a little disconcerting. This is hospice, right? This doesn’t happen in hospice, but unfortunately, it does,” Dr. Brandoff reported.

At the cancer institute, a multidisciplinary task force convened in 2013 has now produced numerous specific policies designed to protect patients and institutions from abuse of controlled pain medications. Those steps are not much different from those being increasingly employed in clinics for nonmalignant chronic pain, but they are applied uniformly in essentially every patient – not just those singled out for high risk.

One required step is the implementation of a prescription-monitoring program for every patient started on a narcotic drug in controlled substances schedule II or III, a benzodiazepine, or a department of public health scheduled IV or V controlled substance. Another is the use of a medication management agreement designed to educate patients about the benefits and risks of controlled substances and outline expectations. All patients and their clinicians are required to sign the agreement.

“If we have someone who is imminently dying within hours or days, then, no, I would not impose a management agreement expectation on them or myself,” said Dr. Brandoff, but he said that there are essentially no other exceptions.

The agreement, crafted with nonjudgmental language aimed at clarifying the goals of chronic pain relief, is entered into the medical record. It generally has been well accepted, according to Dr. Lida Nabati, also a palliative care attending physician at the cancer institute, Dr. Nabati, who participated with Dr. Brandoff in presenting the cancer institute’s safeguards, noted that patient resistance to the agreement often is a red flag for potential problems with abuse.

The movement to control opioid abuse in cancer patients is relatively new. At the time that the task force began, Dr. Nabati noted that few other institutions had formal policies in place even though others also were beginning to review their approach. As recently as 2014, a directive from the Department of Veterans Affairs for opioid therapy in chronic pain patients specifically excluded those with cancer, Dr. Nabati reported.

Yet, cancer “does not afford some magical protective effect” from the very same risk factors associated with opioid use in noncancer patients, such as anxiety, depression, or history of substance use, according to Dr. Brandoff. Rather, he suggested that the added stress of a cancer diagnosis could exacerbate those factors.

The implementation of strategies aimed at reducing the risk of opioid abuse in patients with chronic cancer pain is needed and timely, according to Dr. Mellar P. Davis, the co-chair of the 2015 ICOO meeting and director of the palliative medicine fellowship program, Taussig Cancer Institute, Cleveland Clinic.

In an interview, Dr. Davis applauded the types of strategies implemented at the cancer institute, which he believes protect the patient, the physician, and the institution. He believes that the patients might be the greatest beneficiaries when appropriate opioid use permits a gain in quality of life through effective but nondebilitating pain control.

Dr. Brandoff and Dr. Nabati reported having no financial disclosures.

BOSTON – There may be no area of clinical medicine in which strict adherence to medical standards is more important than in the prescription of opioids.

Rather than malpractice, the consequence of deviations from accepted standards is often criminal prosecution, Dr. Carol A. Warfield said at the International Conference on Opioids.

Some physicians, believing they have acted in the best interests of the patient, have been sent to jail, said Dr. Warfield, professor of anesthesiology at Harvard Medical School, Boston. “Juries don’t seem to understand the difference between malpractice and criminal activity.”

RTEmagicC_8d2c5db_gavel_stethoscope.jpg.jpg

The distinctions are large, she said. In the case of opioids, criminal practice occurs when prescriptions are dispensed without a legitimate medical purpose. Inappropriate prescription of opioids, however, may be malpractice but it is not criminal, particularly if the underlying intent was to relieve patient suffering.

But that distinction is not necessarily recognized in the courtroom. Dr. Warfield recounted numerous criminal cases involving opioids in which the intent of the physician was to relieve pain. Prosecutors in those cases pointed to incomplete records or the lack of a physical examination to convince juries that a crime had been committed.

Often, a criminal prosecution begins with an opioid overdose. Charges may ensue with a review of the medical records that leads prosecutors to believe that standard practices were not followed. But bad outcomes are not essential to trigger an investigation.

Other cases start with an insurance company review, Dr. Warfield cautioned. “High utilization and increased costs push [insurers] to investigate doctors with peer review, and many criminal cases start with an insurance company that thought the clinician was prescribing too much of an expensive drug.”

What can physicians do to protect themselves from these accusations? Ensure that opioids are prescribed within the acceptable standards of practice, which includes first creating a clear physician-patient relationship, Dr. Warfield advised. Opioids should not be prescribed without a physical and history that provides a basis for the diagnosis. And provide clear documentation for each step of care, she emphasized.

Dr. Warfield acknowledged that she “is not a big advocate of using opioids for chronic pain” in her own practice. However, “I am a big advocate of a doctor’s right to do so.”

The risks of malpractice suits and criminal prosecution have already produced some defensive behaviors, inducing a growing number of physicians to abandon opioids altogether, she said. Others will give opioid injections, but will not prescribe opioids in any other form. Still others insist on lengthy consent forms that outline opioid risks.

Dr. Steven J. Bennett, director of pain services at Greenwich (Conn.) Hospital said that he is concerned about the current climate.

“I am very careful in my practice. I document everything,” Dr. Bennett said. However, “opioids are useful in my practice. They can help the right patient, so I am going to keep using them. I just plan to be very careful.”

BOSTON – There may be no area of clinical medicine in which strict adherence to medical standards is more important than in the prescription of opioids.

Rather than malpractice, the consequence of deviations from accepted standards is often criminal prosecution, Dr. Carol A. Warfield said at the International Conference on Opioids.

Some physicians, believing they have acted in the best interests of the patient, have been sent to jail, said Dr. Warfield, professor of anesthesiology at Harvard Medical School, Boston. “Juries don’t seem to understand the difference between malpractice and criminal activity.”

RTEmagicC_8d2c5db_gavel_stethoscope.jpg.jpg

The distinctions are large, she said. In the case of opioids, criminal practice occurs when prescriptions are dispensed without a legitimate medical purpose. Inappropriate prescription of opioids, however, may be malpractice but it is not criminal, particularly if the underlying intent was to relieve patient suffering.

But that distinction is not necessarily recognized in the courtroom. Dr. Warfield recounted numerous criminal cases involving opioids in which the intent of the physician was to relieve pain. Prosecutors in those cases pointed to incomplete records or the lack of a physical examination to convince juries that a crime had been committed.

Often, a criminal prosecution begins with an opioid overdose. Charges may ensue with a review of the medical records that leads prosecutors to believe that standard practices were not followed. But bad outcomes are not essential to trigger an investigation.

Other cases start with an insurance company review, Dr. Warfield cautioned. “High utilization and increased costs push [insurers] to investigate doctors with peer review, and many criminal cases start with an insurance company that thought the clinician was prescribing too much of an expensive drug.”

What can physicians do to protect themselves from these accusations? Ensure that opioids are prescribed within the acceptable standards of practice, which includes first creating a clear physician-patient relationship, Dr. Warfield advised. Opioids should not be prescribed without a physical and history that provides a basis for the diagnosis. And provide clear documentation for each step of care, she emphasized.

Dr. Warfield acknowledged that she “is not a big advocate of using opioids for chronic pain” in her own practice. However, “I am a big advocate of a doctor’s right to do so.”

The risks of malpractice suits and criminal prosecution have already produced some defensive behaviors, inducing a growing number of physicians to abandon opioids altogether, she said. Others will give opioid injections, but will not prescribe opioids in any other form. Still others insist on lengthy consent forms that outline opioid risks.

Dr. Steven J. Bennett, director of pain services at Greenwich (Conn.) Hospital said that he is concerned about the current climate.

“I am very careful in my practice. I document everything,” Dr. Bennett said. However, “opioids are useful in my practice. They can help the right patient, so I am going to keep using them. I just plan to be very careful.”

BOSTON – There may be no area of clinical medicine in which strict adherence to medical standards is more important than in the prescription of opioids.

Rather than malpractice, the consequence of deviations from accepted standards is often criminal prosecution, Dr. Carol A. Warfield said at the International Conference on Opioids.

Some physicians, believing they have acted in the best interests of the patient, have been sent to jail, said Dr. Warfield, professor of anesthesiology at Harvard Medical School, Boston. “Juries don’t seem to understand the difference between malpractice and criminal activity.”

RTEmagicC_8d2c5db_gavel_stethoscope.jpg.jpg

The distinctions are large, she said. In the case of opioids, criminal practice occurs when prescriptions are dispensed without a legitimate medical purpose. Inappropriate prescription of opioids, however, may be malpractice but it is not criminal, particularly if the underlying intent was to relieve patient suffering.

But that distinction is not necessarily recognized in the courtroom. Dr. Warfield recounted numerous criminal cases involving opioids in which the intent of the physician was to relieve pain. Prosecutors in those cases pointed to incomplete records or the lack of a physical examination to convince juries that a crime had been committed.

Often, a criminal prosecution begins with an opioid overdose. Charges may ensue with a review of the medical records that leads prosecutors to believe that standard practices were not followed. But bad outcomes are not essential to trigger an investigation.

Other cases start with an insurance company review, Dr. Warfield cautioned. “High utilization and increased costs push [insurers] to investigate doctors with peer review, and many criminal cases start with an insurance company that thought the clinician was prescribing too much of an expensive drug.”

What can physicians do to protect themselves from these accusations? Ensure that opioids are prescribed within the acceptable standards of practice, which includes first creating a clear physician-patient relationship, Dr. Warfield advised. Opioids should not be prescribed without a physical and history that provides a basis for the diagnosis. And provide clear documentation for each step of care, she emphasized.

Dr. Warfield acknowledged that she “is not a big advocate of using opioids for chronic pain” in her own practice. However, “I am a big advocate of a doctor’s right to do so.”

The risks of malpractice suits and criminal prosecution have already produced some defensive behaviors, inducing a growing number of physicians to abandon opioids altogether, she said. Others will give opioid injections, but will not prescribe opioids in any other form. Still others insist on lengthy consent forms that outline opioid risks.

Dr. Steven J. Bennett, director of pain services at Greenwich (Conn.) Hospital said that he is concerned about the current climate.

“I am very careful in my practice. I document everything,” Dr. Bennett said. However, “opioids are useful in my practice. They can help the right patient, so I am going to keep using them. I just plan to be very careful.”

BOSTON – In an ongoing study that is enrolling patients with highly refractory chronic pain, treatments selected on the basis of objective evidence of underlying genetic defects or other obstacles to pain control are yielding high rates of success, according to the director of the center where the study is underway.

In the 61 patients who underwent an evaluation of hormone activity, 80.3% had one or more abnormalities. For individual hormones tested, the rate of abnormalities was 27.3% for ATCH (adrenocorticotropic hormone), 20.8% for pregnenolone, 37.2% for DHEA (dehydroepiandrosterone), 37.2% for testosterone, 32.8% for cortisol, and 20.8% for progesterone. In most cases, the abnormality was reduced hormone level or activity, but about half of those with cortisol abnormalities had elevated activity.

In 80 patients tested for inflammatory markers, C-reactive protein was elevated in 32.5%, the erythrocyte sedimentation rate was elevated in 27.5%, and tumor necrosis factor–alpha was elevated in 25%. Two or more inflammatory biomarkers were elevated in 31.3%, according to Dr. Forest Tennant, director, Veract Intractable Pain Clinic, Los Angeles.

These findings provided the basis for analgesia selection. No test result assured that any single therapy would be effective, but the objective studies guided a rational approach that narrowed choices, according to Dr. Tennant.

“In our hands, we had to take each patient and find their own suit of clothes,” he said. He acknowledged that some of the analgesia regimens ultimately reached through these kinds of tests have been unorthodox, but the success rate in a very difficult population supports this approach.

“Rather than calling these people drug seekers or sending them on, the time has come to try to objectively evaluate the basis of their resistance to therapy,” Dr. Tennant said.

The strategy, although promising, needs to be clarified and reproduced in a broader number of settings, according to Dr. Gavril W. Pasternak, laboratory head, molecular pharmacology and chemistry, Memorial Sloan-Kettering Cancer Institute in New York. Of 101 patients enrolled since the study’s initiation in 2012, all but two or three have achieved improved pain control after therapies were adjusted on the basis of a series of objective studies that identified barriers to analgesic response, according to Dr. Tennant. He summarized the experience to date at the International Conference on Opioids.

The study has enrolled the hard cases, said Dr. Tennant. All were required to be pain treatment “failures,” defined as patients with an inability to maintain activities of daily living after treatment with multiple nonopioid therapies and an oral opioid dosage of at least 100 mg of morphine milligram equivalents.

Providing a flavor of the types of patients in this study, Dr. Tennant said that the first 40 enrolled had consulted 461 physicians, 172 pain specialists, and 104 mental health specialists. He said clinicians typically avoid this type of pain population and sometimes stigmatize such patients with terms such as “difficult” or “noncooperative.” All had centralized pain for at least 2 years and failure on one or more agents in every class of analgesic.

The research objective of the study was to develop a systematic and objective methodology for evaluating underlying defects leading to pain refractory to opioids in low or moderate doses. This included pharmacogenomics testing of CYP450 and Mu opioid receptor gene functions. It further included studies of hormone function, inflammatory activity, and metabolic biomarkers.

Abnormalities were common. Genetic defects in CYP2D6, CYP2C19, and CYP2C9, for example, were found in 90.1% of the 101 patients evaluated so far. Of these, 27.7% had defects in two and 7.9% had defects in all three, according to Dr. Tennant.

In the 45 patients who underwent pharmacodynamics genetic testing for OPRM1, 28.9% were found to have intermediate or low sensitivity, suggesting an impaired response. In the same patients, 62.2% had intermediate or high activity of catechol-o-methyltransferase activity, which is associated with an increased sensitivity to pain. In an interview after the presentation, Dr. Pasternak said he was intrigued but not fully convinced by the data presented.

According to Dr. Pasternak, the concept of evaluating refractory pain patients with a panel of tests looking at pharmacogenetics, hormones, and inflammatory markers is “interesting” and deserves further evaluation in well-validated studies, but he added, “let’s see if it leads anywhere.”

BOSTON – In an ongoing study that is enrolling patients with highly refractory chronic pain, treatments selected on the basis of objective evidence of underlying genetic defects or other obstacles to pain control are yielding high rates of success, according to the director of the center where the study is underway.

In the 61 patients who underwent an evaluation of hormone activity, 80.3% had one or more abnormalities. For individual hormones tested, the rate of abnormalities was 27.3% for ATCH (adrenocorticotropic hormone), 20.8% for pregnenolone, 37.2% for DHEA (dehydroepiandrosterone), 37.2% for testosterone, 32.8% for cortisol, and 20.8% for progesterone. In most cases, the abnormality was reduced hormone level or activity, but about half of those with cortisol abnormalities had elevated activity.

In 80 patients tested for inflammatory markers, C-reactive protein was elevated in 32.5%, the erythrocyte sedimentation rate was elevated in 27.5%, and tumor necrosis factor–alpha was elevated in 25%. Two or more inflammatory biomarkers were elevated in 31.3%, according to Dr. Forest Tennant, director, Veract Intractable Pain Clinic, Los Angeles.

These findings provided the basis for analgesia selection. No test result assured that any single therapy would be effective, but the objective studies guided a rational approach that narrowed choices, according to Dr. Tennant.

“In our hands, we had to take each patient and find their own suit of clothes,” he said. He acknowledged that some of the analgesia regimens ultimately reached through these kinds of tests have been unorthodox, but the success rate in a very difficult population supports this approach.

“Rather than calling these people drug seekers or sending them on, the time has come to try to objectively evaluate the basis of their resistance to therapy,” Dr. Tennant said.

The strategy, although promising, needs to be clarified and reproduced in a broader number of settings, according to Dr. Gavril W. Pasternak, laboratory head, molecular pharmacology and chemistry, Memorial Sloan-Kettering Cancer Institute in New York. Of 101 patients enrolled since the study’s initiation in 2012, all but two or three have achieved improved pain control after therapies were adjusted on the basis of a series of objective studies that identified barriers to analgesic response, according to Dr. Tennant. He summarized the experience to date at the International Conference on Opioids.

The study has enrolled the hard cases, said Dr. Tennant. All were required to be pain treatment “failures,” defined as patients with an inability to maintain activities of daily living after treatment with multiple nonopioid therapies and an oral opioid dosage of at least 100 mg of morphine milligram equivalents.

Providing a flavor of the types of patients in this study, Dr. Tennant said that the first 40 enrolled had consulted 461 physicians, 172 pain specialists, and 104 mental health specialists. He said clinicians typically avoid this type of pain population and sometimes stigmatize such patients with terms such as “difficult” or “noncooperative.” All had centralized pain for at least 2 years and failure on one or more agents in every class of analgesic.

The research objective of the study was to develop a systematic and objective methodology for evaluating underlying defects leading to pain refractory to opioids in low or moderate doses. This included pharmacogenomics testing of CYP450 and Mu opioid receptor gene functions. It further included studies of hormone function, inflammatory activity, and metabolic biomarkers.

Abnormalities were common. Genetic defects in CYP2D6, CYP2C19, and CYP2C9, for example, were found in 90.1% of the 101 patients evaluated so far. Of these, 27.7% had defects in two and 7.9% had defects in all three, according to Dr. Tennant.

In the 45 patients who underwent pharmacodynamics genetic testing for OPRM1, 28.9% were found to have intermediate or low sensitivity, suggesting an impaired response. In the same patients, 62.2% had intermediate or high activity of catechol-o-methyltransferase activity, which is associated with an increased sensitivity to pain. In an interview after the presentation, Dr. Pasternak said he was intrigued but not fully convinced by the data presented.

According to Dr. Pasternak, the concept of evaluating refractory pain patients with a panel of tests looking at pharmacogenetics, hormones, and inflammatory markers is “interesting” and deserves further evaluation in well-validated studies, but he added, “let’s see if it leads anywhere.”

BOSTON – In an ongoing study that is enrolling patients with highly refractory chronic pain, treatments selected on the basis of objective evidence of underlying genetic defects or other obstacles to pain control are yielding high rates of success, according to the director of the center where the study is underway.

In the 61 patients who underwent an evaluation of hormone activity, 80.3% had one or more abnormalities. For individual hormones tested, the rate of abnormalities was 27.3% for ATCH (adrenocorticotropic hormone), 20.8% for pregnenolone, 37.2% for DHEA (dehydroepiandrosterone), 37.2% for testosterone, 32.8% for cortisol, and 20.8% for progesterone. In most cases, the abnormality was reduced hormone level or activity, but about half of those with cortisol abnormalities had elevated activity.

In 80 patients tested for inflammatory markers, C-reactive protein was elevated in 32.5%, the erythrocyte sedimentation rate was elevated in 27.5%, and tumor necrosis factor–alpha was elevated in 25%. Two or more inflammatory biomarkers were elevated in 31.3%, according to Dr. Forest Tennant, director, Veract Intractable Pain Clinic, Los Angeles.

These findings provided the basis for analgesia selection. No test result assured that any single therapy would be effective, but the objective studies guided a rational approach that narrowed choices, according to Dr. Tennant.

“In our hands, we had to take each patient and find their own suit of clothes,” he said. He acknowledged that some of the analgesia regimens ultimately reached through these kinds of tests have been unorthodox, but the success rate in a very difficult population supports this approach.

“Rather than calling these people drug seekers or sending them on, the time has come to try to objectively evaluate the basis of their resistance to therapy,” Dr. Tennant said.

The strategy, although promising, needs to be clarified and reproduced in a broader number of settings, according to Dr. Gavril W. Pasternak, laboratory head, molecular pharmacology and chemistry, Memorial Sloan-Kettering Cancer Institute in New York. Of 101 patients enrolled since the study’s initiation in 2012, all but two or three have achieved improved pain control after therapies were adjusted on the basis of a series of objective studies that identified barriers to analgesic response, according to Dr. Tennant. He summarized the experience to date at the International Conference on Opioids.

The study has enrolled the hard cases, said Dr. Tennant. All were required to be pain treatment “failures,” defined as patients with an inability to maintain activities of daily living after treatment with multiple nonopioid therapies and an oral opioid dosage of at least 100 mg of morphine milligram equivalents.

Providing a flavor of the types of patients in this study, Dr. Tennant said that the first 40 enrolled had consulted 461 physicians, 172 pain specialists, and 104 mental health specialists. He said clinicians typically avoid this type of pain population and sometimes stigmatize such patients with terms such as “difficult” or “noncooperative.” All had centralized pain for at least 2 years and failure on one or more agents in every class of analgesic.

The research objective of the study was to develop a systematic and objective methodology for evaluating underlying defects leading to pain refractory to opioids in low or moderate doses. This included pharmacogenomics testing of CYP450 and Mu opioid receptor gene functions. It further included studies of hormone function, inflammatory activity, and metabolic biomarkers.

Abnormalities were common. Genetic defects in CYP2D6, CYP2C19, and CYP2C9, for example, were found in 90.1% of the 101 patients evaluated so far. Of these, 27.7% had defects in two and 7.9% had defects in all three, according to Dr. Tennant.

In the 45 patients who underwent pharmacodynamics genetic testing for OPRM1, 28.9% were found to have intermediate or low sensitivity, suggesting an impaired response. In the same patients, 62.2% had intermediate or high activity of catechol-o-methyltransferase activity, which is associated with an increased sensitivity to pain. In an interview after the presentation, Dr. Pasternak said he was intrigued but not fully convinced by the data presented.

According to Dr. Pasternak, the concept of evaluating refractory pain patients with a panel of tests looking at pharmacogenetics, hormones, and inflammatory markers is “interesting” and deserves further evaluation in well-validated studies, but he added, “let’s see if it leads anywhere.”

BOSTON – Medical marijuana is now legal in 23 states, but there remains essentially no systematic approach for evaluating whether available products have the capacity to provide medical benefits, according to a status report presented at the International Conference on Opioids.

Often, medical marijuana is marketed on the basis of its psychoactive component, tetrahydrocannabinol (THC), but a substantial body of data suggests that it is the cannabidiol (CBD) content that is most responsible for appetite stimulation, antiemetic effects, and many other medicinal properties, according to Michael E. Schatman, Ph.D., executive director of the Foundation for Ethics in Pain Care, Bellevue, Wash.

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“Contrary to popular belief, THC is not the most relevant cannabinoid for medical application,” Dr. Schatman said. On the premise that more is better, higher THC content generally correlates with higher cost for medical marijuana as it does for marijuana marketed for recreational use, according to Dr. Schatman. But he disagreed with that notion.

More than 100 cannabinoids are in marijuana, Dr. Schatman said. Although he maintained that CBD might be the most important constituent for many of the medicinal indications for marijuana, he acknowledged that the data are mostly suggestive. Few studies have differentiated marijuana for its therapeutic effects based on representative concentrations of different constituents even if Dr. Schatman cited clinical and experimental work correlating CBD with benefit on a variety of therapeutic targets, including inflammation.

“There is no medical marijuana but medical marijuanas,” said Dr. Schatman, suggesting that specific therapeutic benefits would be expected to differ markedly according to the constituents even if little information exists about the optimal levels of any of these constituents.

For recreational use, THC content is a reasonable quality metric, Dr. Schatman said. THC content predicts the “high” of marijuana. While inducing a state of euphoria might indeed be the goal for some medicinal marijuana applications, high THC content also poses the greatest risk of psychosis, disordered thoughts, and impaired functionality, he said. To this extent, greater THC content might not predict greater benefit.

In the absence of regulatory oversight, the marketing of marijuana rather than the science of its effect dominates all discussion, Dr. Schatman said. He cited data showing a steep increase in THC content subsequent to the growing rate of state legalizations.

“Dispensaries are selling medical marijuana with THC contents as high as 33% with names like Super Brain Damage OG,” Dr. Schatman said. Given the potential for unwanted side effects at THC dose levels likely to impair cognitive function, Dr. Schatman said it might be reasonable to question the therapeutic intent when products feature THC content at levels this high.

So far, only New Jersey has restricted THC content of medical marijuana, placing the ceiling at 10%, Dr. Schatman said. Compared to the 1970s, when street marijuana typically had THC content of about 1% to 2%, Dr. Schatman suggested that even 10% is likely to be excessive if the goal is not be get “stoned.” However, he expressed even greater concern about the declining content of CBD, which he suggested has been inversely related to THC.

“We’ve essentially bred the CBD out of marijuana,” Dr. Schatman reported. One advertisement from a medical marijuana dispensary that he reproduced prominently advertised THC levels at 20% but CBD levels at 0.38%. Whether greater medicinal benefits would be realized if those percentages were reversed is not known, but Dr. Schatman said rational clinical decisions are impossible without data.

“Until the patient knows what he or she is getting, cannabis will not necessarily be medicine in most cases,” Dr. Schatman said. He believes the marijuana should be held to the same standards of efficacy and safety as other drugs. The ideal for moving this field forward might be regulation by the Food and Drug Administration, Dr. Schatman said. But he also called for more rigorous trials of the marijuana constituents to determine which are most important for achieving the specific benefits for which marijuana is being prescribed.

Dr. Schatman is on the speaker’s bureau for Mallinckrodt.

BOSTON – Medical marijuana is now legal in 23 states, but there remains essentially no systematic approach for evaluating whether available products have the capacity to provide medical benefits, according to a status report presented at the International Conference on Opioids.

Often, medical marijuana is marketed on the basis of its psychoactive component, tetrahydrocannabinol (THC), but a substantial body of data suggests that it is the cannabidiol (CBD) content that is most responsible for appetite stimulation, antiemetic effects, and many other medicinal properties, according to Michael E. Schatman, Ph.D., executive director of the Foundation for Ethics in Pain Care, Bellevue, Wash.

RTEmagicC_40cd3c3_marijuana_medical.jpg.jpg

“Contrary to popular belief, THC is not the most relevant cannabinoid for medical application,” Dr. Schatman said. On the premise that more is better, higher THC content generally correlates with higher cost for medical marijuana as it does for marijuana marketed for recreational use, according to Dr. Schatman. But he disagreed with that notion.

More than 100 cannabinoids are in marijuana, Dr. Schatman said. Although he maintained that CBD might be the most important constituent for many of the medicinal indications for marijuana, he acknowledged that the data are mostly suggestive. Few studies have differentiated marijuana for its therapeutic effects based on representative concentrations of different constituents even if Dr. Schatman cited clinical and experimental work correlating CBD with benefit on a variety of therapeutic targets, including inflammation.

“There is no medical marijuana but medical marijuanas,” said Dr. Schatman, suggesting that specific therapeutic benefits would be expected to differ markedly according to the constituents even if little information exists about the optimal levels of any of these constituents.

For recreational use, THC content is a reasonable quality metric, Dr. Schatman said. THC content predicts the “high” of marijuana. While inducing a state of euphoria might indeed be the goal for some medicinal marijuana applications, high THC content also poses the greatest risk of psychosis, disordered thoughts, and impaired functionality, he said. To this extent, greater THC content might not predict greater benefit.

In the absence of regulatory oversight, the marketing of marijuana rather than the science of its effect dominates all discussion, Dr. Schatman said. He cited data showing a steep increase in THC content subsequent to the growing rate of state legalizations.

“Dispensaries are selling medical marijuana with THC contents as high as 33% with names like Super Brain Damage OG,” Dr. Schatman said. Given the potential for unwanted side effects at THC dose levels likely to impair cognitive function, Dr. Schatman said it might be reasonable to question the therapeutic intent when products feature THC content at levels this high.

So far, only New Jersey has restricted THC content of medical marijuana, placing the ceiling at 10%, Dr. Schatman said. Compared to the 1970s, when street marijuana typically had THC content of about 1% to 2%, Dr. Schatman suggested that even 10% is likely to be excessive if the goal is not be get “stoned.” However, he expressed even greater concern about the declining content of CBD, which he suggested has been inversely related to THC.

“We’ve essentially bred the CBD out of marijuana,” Dr. Schatman reported. One advertisement from a medical marijuana dispensary that he reproduced prominently advertised THC levels at 20% but CBD levels at 0.38%. Whether greater medicinal benefits would be realized if those percentages were reversed is not known, but Dr. Schatman said rational clinical decisions are impossible without data.

“Until the patient knows what he or she is getting, cannabis will not necessarily be medicine in most cases,” Dr. Schatman said. He believes the marijuana should be held to the same standards of efficacy and safety as other drugs. The ideal for moving this field forward might be regulation by the Food and Drug Administration, Dr. Schatman said. But he also called for more rigorous trials of the marijuana constituents to determine which are most important for achieving the specific benefits for which marijuana is being prescribed.

Dr. Schatman is on the speaker’s bureau for Mallinckrodt.

BOSTON – Medical marijuana is now legal in 23 states, but there remains essentially no systematic approach for evaluating whether available products have the capacity to provide medical benefits, according to a status report presented at the International Conference on Opioids.

Often, medical marijuana is marketed on the basis of its psychoactive component, tetrahydrocannabinol (THC), but a substantial body of data suggests that it is the cannabidiol (CBD) content that is most responsible for appetite stimulation, antiemetic effects, and many other medicinal properties, according to Michael E. Schatman, Ph.D., executive director of the Foundation for Ethics in Pain Care, Bellevue, Wash.

RTEmagicC_40cd3c3_marijuana_medical.jpg.jpg

“Contrary to popular belief, THC is not the most relevant cannabinoid for medical application,” Dr. Schatman said. On the premise that more is better, higher THC content generally correlates with higher cost for medical marijuana as it does for marijuana marketed for recreational use, according to Dr. Schatman. But he disagreed with that notion.

More than 100 cannabinoids are in marijuana, Dr. Schatman said. Although he maintained that CBD might be the most important constituent for many of the medicinal indications for marijuana, he acknowledged that the data are mostly suggestive. Few studies have differentiated marijuana for its therapeutic effects based on representative concentrations of different constituents even if Dr. Schatman cited clinical and experimental work correlating CBD with benefit on a variety of therapeutic targets, including inflammation.

“There is no medical marijuana but medical marijuanas,” said Dr. Schatman, suggesting that specific therapeutic benefits would be expected to differ markedly according to the constituents even if little information exists about the optimal levels of any of these constituents.

For recreational use, THC content is a reasonable quality metric, Dr. Schatman said. THC content predicts the “high” of marijuana. While inducing a state of euphoria might indeed be the goal for some medicinal marijuana applications, high THC content also poses the greatest risk of psychosis, disordered thoughts, and impaired functionality, he said. To this extent, greater THC content might not predict greater benefit.

In the absence of regulatory oversight, the marketing of marijuana rather than the science of its effect dominates all discussion, Dr. Schatman said. He cited data showing a steep increase in THC content subsequent to the growing rate of state legalizations.

“Dispensaries are selling medical marijuana with THC contents as high as 33% with names like Super Brain Damage OG,” Dr. Schatman said. Given the potential for unwanted side effects at THC dose levels likely to impair cognitive function, Dr. Schatman said it might be reasonable to question the therapeutic intent when products feature THC content at levels this high.

So far, only New Jersey has restricted THC content of medical marijuana, placing the ceiling at 10%, Dr. Schatman said. Compared to the 1970s, when street marijuana typically had THC content of about 1% to 2%, Dr. Schatman suggested that even 10% is likely to be excessive if the goal is not be get “stoned.” However, he expressed even greater concern about the declining content of CBD, which he suggested has been inversely related to THC.

“We’ve essentially bred the CBD out of marijuana,” Dr. Schatman reported. One advertisement from a medical marijuana dispensary that he reproduced prominently advertised THC levels at 20% but CBD levels at 0.38%. Whether greater medicinal benefits would be realized if those percentages were reversed is not known, but Dr. Schatman said rational clinical decisions are impossible without data.

“Until the patient knows what he or she is getting, cannabis will not necessarily be medicine in most cases,” Dr. Schatman said. He believes the marijuana should be held to the same standards of efficacy and safety as other drugs. The ideal for moving this field forward might be regulation by the Food and Drug Administration, Dr. Schatman said. But he also called for more rigorous trials of the marijuana constituents to determine which are most important for achieving the specific benefits for which marijuana is being prescribed.

Dr. Schatman is on the speaker’s bureau for Mallinckrodt.

BOSTON – The discomfort among primary care physicians managing patients on opioids is not necessarily mitigated with greater support from pain specialists, according to a study that tracked attitudes before and after an initiative specifically designed to increase that support.

The study, presented at the International Conference on Opioids, surveyed 56 primary care clinicians before and after the initiative, according to Robert Jamison, Ph.D., professor in the departments of anesthesia, psychiatry, and physician medicine and rehabilitation at Harvard Medical School in Boston.

The study, according to Dr. Jamison, was based on the observation that primary care physicians are uncomfortable prescribing opioids even after a pain specialist has recommended this therapy.

“A lot of primary care physicians don’t like pain specialists,” Dr. Jamison said. The reason, he explained, is that they are uncomfortable prescribing or managing opioids in patients with chronic pain, and they think that pain specialists provide them with little support.

In a study that involved 56 primary care physicians and 253 chronic pain patients that they referred, a baseline survey showed that less than 20% of the physicians reported formal training in pain management. In addition, 80% reported that they considered treating chronic pain to be a challenge, and nearly 70% reported that they feared prescribing opioids because of the risk of addiction. In addition, 62.5% reported that they were dissatisfied with their past consults with pain specialists.

After the survey, a program was initiated to provide support for opioid management in the referred chronic pain patients. This involved evaluating and initiating a pain management program that included screening patients for risk of opioid misuse. Although all the patients were potential candidates for opioids based on clinical characteristics, only 207 ultimately received opioids.

With patient management, the program also provided the participating primary care physicians with guidance on managing chronic pain with opioids.

The chronic pain patients were contacted monthly by telephone to evaluate compliance and risk of opioid misuse. Follow-up was maintained over 6 months. The 33 primary care physicians linked to the Harvard electronic medical records system were provided with monthly status reports about the opioid patients in their care.

When the primary care physicians were surveyed at the end of 6 months, there was essentially no change in attitude in regard to the challenges of managing patients on opioids, including fear of patient addiction or the physician’s confidence in his or her ability to identify patients at risk of addiction.

Physicians did, however, express improved sense of support from pain specialists. For example, the initial 62.5% rate of dissatisfaction with communication with pain specialists fell to 23.4%. In addition, physician comfort with opioids more than tripled, rising from 7.2% to 23.4%. However, this suggested that 75% of physicians were still uncomfortable.

“So we did get some mixed results on our intervention,” acknowledged Dr. Jamison, who noted that the data from this recently completed study are still being analyzed. He did note that satisfaction overall with pain-specialist communication was greatest in those physicians who received monthly reports.

Based on the data analyzed to date, the findings might be best interpreted “as a heads-up for pain specialists in the room to say that primary care physicians don’t feel that they are getting the support that they need,” Dr. Jamison reported.

The study was investigator initiated. Dr. Jamison reported having no financial disclosures.

BOSTON – The discomfort among primary care physicians managing patients on opioids is not necessarily mitigated with greater support from pain specialists, according to a study that tracked attitudes before and after an initiative specifically designed to increase that support.

The study, presented at the International Conference on Opioids, surveyed 56 primary care clinicians before and after the initiative, according to Robert Jamison, Ph.D., professor in the departments of anesthesia, psychiatry, and physician medicine and rehabilitation at Harvard Medical School in Boston.

The study, according to Dr. Jamison, was based on the observation that primary care physicians are uncomfortable prescribing opioids even after a pain specialist has recommended this therapy.

“A lot of primary care physicians don’t like pain specialists,” Dr. Jamison said. The reason, he explained, is that they are uncomfortable prescribing or managing opioids in patients with chronic pain, and they think that pain specialists provide them with little support.

In a study that involved 56 primary care physicians and 253 chronic pain patients that they referred, a baseline survey showed that less than 20% of the physicians reported formal training in pain management. In addition, 80% reported that they considered treating chronic pain to be a challenge, and nearly 70% reported that they feared prescribing opioids because of the risk of addiction. In addition, 62.5% reported that they were dissatisfied with their past consults with pain specialists.

After the survey, a program was initiated to provide support for opioid management in the referred chronic pain patients. This involved evaluating and initiating a pain management program that included screening patients for risk of opioid misuse. Although all the patients were potential candidates for opioids based on clinical characteristics, only 207 ultimately received opioids.

With patient management, the program also provided the participating primary care physicians with guidance on managing chronic pain with opioids.

The chronic pain patients were contacted monthly by telephone to evaluate compliance and risk of opioid misuse. Follow-up was maintained over 6 months. The 33 primary care physicians linked to the Harvard electronic medical records system were provided with monthly status reports about the opioid patients in their care.

When the primary care physicians were surveyed at the end of 6 months, there was essentially no change in attitude in regard to the challenges of managing patients on opioids, including fear of patient addiction or the physician’s confidence in his or her ability to identify patients at risk of addiction.

Physicians did, however, express improved sense of support from pain specialists. For example, the initial 62.5% rate of dissatisfaction with communication with pain specialists fell to 23.4%. In addition, physician comfort with opioids more than tripled, rising from 7.2% to 23.4%. However, this suggested that 75% of physicians were still uncomfortable.

“So we did get some mixed results on our intervention,” acknowledged Dr. Jamison, who noted that the data from this recently completed study are still being analyzed. He did note that satisfaction overall with pain-specialist communication was greatest in those physicians who received monthly reports.

Based on the data analyzed to date, the findings might be best interpreted “as a heads-up for pain specialists in the room to say that primary care physicians don’t feel that they are getting the support that they need,” Dr. Jamison reported.

The study was investigator initiated. Dr. Jamison reported having no financial disclosures.

BOSTON – The discomfort among primary care physicians managing patients on opioids is not necessarily mitigated with greater support from pain specialists, according to a study that tracked attitudes before and after an initiative specifically designed to increase that support.

The study, presented at the International Conference on Opioids, surveyed 56 primary care clinicians before and after the initiative, according to Robert Jamison, Ph.D., professor in the departments of anesthesia, psychiatry, and physician medicine and rehabilitation at Harvard Medical School in Boston.

The study, according to Dr. Jamison, was based on the observation that primary care physicians are uncomfortable prescribing opioids even after a pain specialist has recommended this therapy.

“A lot of primary care physicians don’t like pain specialists,” Dr. Jamison said. The reason, he explained, is that they are uncomfortable prescribing or managing opioids in patients with chronic pain, and they think that pain specialists provide them with little support.

In a study that involved 56 primary care physicians and 253 chronic pain patients that they referred, a baseline survey showed that less than 20% of the physicians reported formal training in pain management. In addition, 80% reported that they considered treating chronic pain to be a challenge, and nearly 70% reported that they feared prescribing opioids because of the risk of addiction. In addition, 62.5% reported that they were dissatisfied with their past consults with pain specialists.

After the survey, a program was initiated to provide support for opioid management in the referred chronic pain patients. This involved evaluating and initiating a pain management program that included screening patients for risk of opioid misuse. Although all the patients were potential candidates for opioids based on clinical characteristics, only 207 ultimately received opioids.

With patient management, the program also provided the participating primary care physicians with guidance on managing chronic pain with opioids.

The chronic pain patients were contacted monthly by telephone to evaluate compliance and risk of opioid misuse. Follow-up was maintained over 6 months. The 33 primary care physicians linked to the Harvard electronic medical records system were provided with monthly status reports about the opioid patients in their care.

When the primary care physicians were surveyed at the end of 6 months, there was essentially no change in attitude in regard to the challenges of managing patients on opioids, including fear of patient addiction or the physician’s confidence in his or her ability to identify patients at risk of addiction.

Physicians did, however, express improved sense of support from pain specialists. For example, the initial 62.5% rate of dissatisfaction with communication with pain specialists fell to 23.4%. In addition, physician comfort with opioids more than tripled, rising from 7.2% to 23.4%. However, this suggested that 75% of physicians were still uncomfortable.

“So we did get some mixed results on our intervention,” acknowledged Dr. Jamison, who noted that the data from this recently completed study are still being analyzed. He did note that satisfaction overall with pain-specialist communication was greatest in those physicians who received monthly reports.

Based on the data analyzed to date, the findings might be best interpreted “as a heads-up for pain specialists in the room to say that primary care physicians don’t feel that they are getting the support that they need,” Dr. Jamison reported.

The study was investigator initiated. Dr. Jamison reported having no financial disclosures.

BOSTON – A patient care process initiated to ensure that opioid prescriptions adhere to high standards of appropriate use and safety has potentially improved the quality of pain management while increasing revenue, according to a detailed analysis of the initiative presented at the International Conference on Opioids.

The process, started 2 years ago in a pilot program, involves a series of steps to evaluate pain patients for their suitability for opioids and then monitor their course of care, said Dr. William G. Brose, an adjunct clinical professor at Stanford (Calif.) University and chief executive officer of the HELP Pain Medical Network.

The process, called the Analgesic Adherence Program (AAP), was constructed out of published guidelines and standards of care, particularly those issued for opioid use by the medical board of the state of California, where the for-profit HELP Pain Medical Network has more than 30 locations. Concern about liability from prescribing opioids was a major impetus for development of the AAP.

“I wanted to try to keep myself safe, to try to keep my patients safe, and to try to keep my practice secure,” Dr. Brose explained.

The process begins with initial risk stratification for which the Medical Board of California specifies the tools. Other states might specify different tools or no tools, although every state has now established recommendations for the use of opioids, except Alaska and Illinois, Dr. Brose said. He said 18 of those guidelines have been updated in the last 4 years, and those following his lead should adhere to state-specific standards.

Subsequent steps include educating patients about the risks and benefits of opioids, seeking informed consent, and then selecting a monitoring program suitable to the patient’s circumstances. Throughout each process, the AAP includes detailed decision trees, including the option to refer patients to specialists if a risk level exceeds the comfort level of the clinician or institution.

Most of these steps, such as risk assessment and seeking informed consent, are billable and performed by nonphysicians. This was captured in an evaluation of 192 new patients and 662 established patients entered into the AAP process over the past 12 months. Relative to usual management, physician time was essentially unchanged, even though time spent by nonphysician clinicians, coders, and billers, rose.

As a result of the AAP, the tasks of the pain specialists have shifted. According to Dr. Brose, his job and the job of other pain specialist physicians in his network is “basically exception management.” This means that Dr. Brose focuses his attention on “the people who are not doing what they are supposed to be doing.”

Those patients, Dr. Brose said, are the more interesting ones, and this approach results in the most efficient use of physician time.

The AAP was created by Dr. Brose for the HELP Pain Medical Network to address growing concern about the medicolegal risks from prescribing opioids. Dr. Brose reported that increased revenue for the network has been a byproduct. Although the implementation of AAP has been associated with some increased costs, average per-year billing for new chronic pain patients evaluated for opioid prescriptions has climbed from $900 to $1,950 per year. For established patients, per-year billing climbed from $600 to $1,300.

“If you go through the effort to establish this kind of process, you’ll increase your revenue and you will be delivering safer, more effective, consistent monitored care,” Dr. Brose said.

Dr. Brose is a stockholder in the HELP Pain Medical Network.

BOSTON – A patient care process initiated to ensure that opioid prescriptions adhere to high standards of appropriate use and safety has potentially improved the quality of pain management while increasing revenue, according to a detailed analysis of the initiative presented at the International Conference on Opioids.

The process, started 2 years ago in a pilot program, involves a series of steps to evaluate pain patients for their suitability for opioids and then monitor their course of care, said Dr. William G. Brose, an adjunct clinical professor at Stanford (Calif.) University and chief executive officer of the HELP Pain Medical Network.

The process, called the Analgesic Adherence Program (AAP), was constructed out of published guidelines and standards of care, particularly those issued for opioid use by the medical board of the state of California, where the for-profit HELP Pain Medical Network has more than 30 locations. Concern about liability from prescribing opioids was a major impetus for development of the AAP.

“I wanted to try to keep myself safe, to try to keep my patients safe, and to try to keep my practice secure,” Dr. Brose explained.

The process begins with initial risk stratification for which the Medical Board of California specifies the tools. Other states might specify different tools or no tools, although every state has now established recommendations for the use of opioids, except Alaska and Illinois, Dr. Brose said. He said 18 of those guidelines have been updated in the last 4 years, and those following his lead should adhere to state-specific standards.

Subsequent steps include educating patients about the risks and benefits of opioids, seeking informed consent, and then selecting a monitoring program suitable to the patient’s circumstances. Throughout each process, the AAP includes detailed decision trees, including the option to refer patients to specialists if a risk level exceeds the comfort level of the clinician or institution.

Most of these steps, such as risk assessment and seeking informed consent, are billable and performed by nonphysicians. This was captured in an evaluation of 192 new patients and 662 established patients entered into the AAP process over the past 12 months. Relative to usual management, physician time was essentially unchanged, even though time spent by nonphysician clinicians, coders, and billers, rose.

As a result of the AAP, the tasks of the pain specialists have shifted. According to Dr. Brose, his job and the job of other pain specialist physicians in his network is “basically exception management.” This means that Dr. Brose focuses his attention on “the people who are not doing what they are supposed to be doing.”

Those patients, Dr. Brose said, are the more interesting ones, and this approach results in the most efficient use of physician time.

The AAP was created by Dr. Brose for the HELP Pain Medical Network to address growing concern about the medicolegal risks from prescribing opioids. Dr. Brose reported that increased revenue for the network has been a byproduct. Although the implementation of AAP has been associated with some increased costs, average per-year billing for new chronic pain patients evaluated for opioid prescriptions has climbed from $900 to $1,950 per year. For established patients, per-year billing climbed from $600 to $1,300.

“If you go through the effort to establish this kind of process, you’ll increase your revenue and you will be delivering safer, more effective, consistent monitored care,” Dr. Brose said.

Dr. Brose is a stockholder in the HELP Pain Medical Network.

BOSTON – A patient care process initiated to ensure that opioid prescriptions adhere to high standards of appropriate use and safety has potentially improved the quality of pain management while increasing revenue, according to a detailed analysis of the initiative presented at the International Conference on Opioids.

The process, started 2 years ago in a pilot program, involves a series of steps to evaluate pain patients for their suitability for opioids and then monitor their course of care, said Dr. William G. Brose, an adjunct clinical professor at Stanford (Calif.) University and chief executive officer of the HELP Pain Medical Network.

The process, called the Analgesic Adherence Program (AAP), was constructed out of published guidelines and standards of care, particularly those issued for opioid use by the medical board of the state of California, where the for-profit HELP Pain Medical Network has more than 30 locations. Concern about liability from prescribing opioids was a major impetus for development of the AAP.

“I wanted to try to keep myself safe, to try to keep my patients safe, and to try to keep my practice secure,” Dr. Brose explained.

The process begins with initial risk stratification for which the Medical Board of California specifies the tools. Other states might specify different tools or no tools, although every state has now established recommendations for the use of opioids, except Alaska and Illinois, Dr. Brose said. He said 18 of those guidelines have been updated in the last 4 years, and those following his lead should adhere to state-specific standards.

Subsequent steps include educating patients about the risks and benefits of opioids, seeking informed consent, and then selecting a monitoring program suitable to the patient’s circumstances. Throughout each process, the AAP includes detailed decision trees, including the option to refer patients to specialists if a risk level exceeds the comfort level of the clinician or institution.

Most of these steps, such as risk assessment and seeking informed consent, are billable and performed by nonphysicians. This was captured in an evaluation of 192 new patients and 662 established patients entered into the AAP process over the past 12 months. Relative to usual management, physician time was essentially unchanged, even though time spent by nonphysician clinicians, coders, and billers, rose.

As a result of the AAP, the tasks of the pain specialists have shifted. According to Dr. Brose, his job and the job of other pain specialist physicians in his network is “basically exception management.” This means that Dr. Brose focuses his attention on “the people who are not doing what they are supposed to be doing.”

Those patients, Dr. Brose said, are the more interesting ones, and this approach results in the most efficient use of physician time.

The AAP was created by Dr. Brose for the HELP Pain Medical Network to address growing concern about the medicolegal risks from prescribing opioids. Dr. Brose reported that increased revenue for the network has been a byproduct. Although the implementation of AAP has been associated with some increased costs, average per-year billing for new chronic pain patients evaluated for opioid prescriptions has climbed from $900 to $1,950 per year. For established patients, per-year billing climbed from $600 to $1,300.

“If you go through the effort to establish this kind of process, you’ll increase your revenue and you will be delivering safer, more effective, consistent monitored care,” Dr. Brose said.

Dr. Brose is a stockholder in the HELP Pain Medical Network.

BOSTON – Genetic tests for pain treatment efficacy are being marketed in the United States and Australia, but one expert argues that they are not ready for use in clinical practice.

There is evidence that variability in patient response to opioids is due to pharmacogenomics that define drug metabolism and receptor activity, but it is just one factor that cannot yet be teased out from others, according to a summary by one expert at the International Conference on Opioids.

RTEmagicC_2d082a4_Genes_DNA_1.jpg.jpg

“My view is that commercialization of current genetic tests of pain treatment efficacy with opioids is somewhat premature. Evidence is limited, and I think regulation is necessary,” said Dr. Andrew Somogyi, professor in clinical and experimental pharmacology, University of Adelaide (Australia).

Progress has been made in identifying genetic factors that influence response to opioids, but there are two barriers to clinically useful tools, according to Dr. Somogyi. One is that clinical utility has yet to be proven for any test in a well-designed trial. The other is that even if pharmacogenomics features are relevant, the quality of commercial tests must be validated.

There are now at least two companies marketing genetic tests to guide selection of analgesics in the United States as well as one in Australia, but Dr. Somogyi said that neither the U.S. Food and Drug Administration nor the Australian Therapeutic Goods Administration provides any regulatory oversight. He noted that prices for the testing vary, but he believes that there is no evidence that analgesia can be improved by acting on test results.

As an example, he noted that the company in Australia employs genetic predictors of CYP2D6 function, an enzyme important to opioid metabolism, to estimate benefit from this class of analgesics. However, published studies have not yet generated compelling evidence that this is clinically relevant for either improving pain control or avoiding adverse events.

In the case of oxycodone, studies comparing poor metabolizers to ultra-rapid metabolizers do show important differences in experimental models of pain, but “clinical studies have really shown no effect,” Dr. Somogyi said.

He drew the same conclusion about CYP2D6 function in regard to the effects of codeine and the variants in the OPRM1 gene and their effect on the Mu receptor and response to morphine. In all cases, there are studies to suggest genetic differences are meaningful in experimental models, but no evidence from a clinical study to show that acting on this information changes outcome or otherwise improves care.

Although he acknowledged that it is tempting to believe pharmacogenetics can explain the well-known variability in response to analgesics, “other factors are just swamping these pharmacogenetics variables,” Dr. Somogyi maintained. Not least of these other factors are the psychosocial factors that influence response to pain stimuli.

This does not preclude an eventual role for pharmacogenetics in the selection of analgesics. Dr. Somogyi, who has been working in this area for several decades, outlined a broad array of promising areas of research. It is the current clinical application of pharmacogenetics with which Dr. Somogyi took issue. He criticized many of the marketing claims made on behalf of available tests, which he considers unsubstantiated.

Deferring to the expertise of Dr. Somogyi, Dr. Paul A. Sloan, professor and vice chair for research, University of Kentucky, Lexington, said he found the perspective compelling. In an interview, Dr. Sloan, cochair of the 2015 ICOO meeting, reported that he knows of no one using pharmacogenetics testing to guide analgesic choice, and he reiterated Dr. Somogyi’s concerns about the need to validate the quality of tests as a part of an effort to confirm their viability as clinical tools.

Dr. Somogyi reported having no financial disclosures.

BOSTON – Genetic tests for pain treatment efficacy are being marketed in the United States and Australia, but one expert argues that they are not ready for use in clinical practice.

There is evidence that variability in patient response to opioids is due to pharmacogenomics that define drug metabolism and receptor activity, but it is just one factor that cannot yet be teased out from others, according to a summary by one expert at the International Conference on Opioids.

RTEmagicC_2d082a4_Genes_DNA_1.jpg.jpg

“My view is that commercialization of current genetic tests of pain treatment efficacy with opioids is somewhat premature. Evidence is limited, and I think regulation is necessary,” said Dr. Andrew Somogyi, professor in clinical and experimental pharmacology, University of Adelaide (Australia).

Progress has been made in identifying genetic factors that influence response to opioids, but there are two barriers to clinically useful tools, according to Dr. Somogyi. One is that clinical utility has yet to be proven for any test in a well-designed trial. The other is that even if pharmacogenomics features are relevant, the quality of commercial tests must be validated.

There are now at least two companies marketing genetic tests to guide selection of analgesics in the United States as well as one in Australia, but Dr. Somogyi said that neither the U.S. Food and Drug Administration nor the Australian Therapeutic Goods Administration provides any regulatory oversight. He noted that prices for the testing vary, but he believes that there is no evidence that analgesia can be improved by acting on test results.

As an example, he noted that the company in Australia employs genetic predictors of CYP2D6 function, an enzyme important to opioid metabolism, to estimate benefit from this class of analgesics. However, published studies have not yet generated compelling evidence that this is clinically relevant for either improving pain control or avoiding adverse events.

In the case of oxycodone, studies comparing poor metabolizers to ultra-rapid metabolizers do show important differences in experimental models of pain, but “clinical studies have really shown no effect,” Dr. Somogyi said.

He drew the same conclusion about CYP2D6 function in regard to the effects of codeine and the variants in the OPRM1 gene and their effect on the Mu receptor and response to morphine. In all cases, there are studies to suggest genetic differences are meaningful in experimental models, but no evidence from a clinical study to show that acting on this information changes outcome or otherwise improves care.

Although he acknowledged that it is tempting to believe pharmacogenetics can explain the well-known variability in response to analgesics, “other factors are just swamping these pharmacogenetics variables,” Dr. Somogyi maintained. Not least of these other factors are the psychosocial factors that influence response to pain stimuli.

This does not preclude an eventual role for pharmacogenetics in the selection of analgesics. Dr. Somogyi, who has been working in this area for several decades, outlined a broad array of promising areas of research. It is the current clinical application of pharmacogenetics with which Dr. Somogyi took issue. He criticized many of the marketing claims made on behalf of available tests, which he considers unsubstantiated.

Deferring to the expertise of Dr. Somogyi, Dr. Paul A. Sloan, professor and vice chair for research, University of Kentucky, Lexington, said he found the perspective compelling. In an interview, Dr. Sloan, cochair of the 2015 ICOO meeting, reported that he knows of no one using pharmacogenetics testing to guide analgesic choice, and he reiterated Dr. Somogyi’s concerns about the need to validate the quality of tests as a part of an effort to confirm their viability as clinical tools.

Dr. Somogyi reported having no financial disclosures.

BOSTON – Genetic tests for pain treatment efficacy are being marketed in the United States and Australia, but one expert argues that they are not ready for use in clinical practice.

There is evidence that variability in patient response to opioids is due to pharmacogenomics that define drug metabolism and receptor activity, but it is just one factor that cannot yet be teased out from others, according to a summary by one expert at the International Conference on Opioids.

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“My view is that commercialization of current genetic tests of pain treatment efficacy with opioids is somewhat premature. Evidence is limited, and I think regulation is necessary,” said Dr. Andrew Somogyi, professor in clinical and experimental pharmacology, University of Adelaide (Australia).

Progress has been made in identifying genetic factors that influence response to opioids, but there are two barriers to clinically useful tools, according to Dr. Somogyi. One is that clinical utility has yet to be proven for any test in a well-designed trial. The other is that even if pharmacogenomics features are relevant, the quality of commercial tests must be validated.

There are now at least two companies marketing genetic tests to guide selection of analgesics in the United States as well as one in Australia, but Dr. Somogyi said that neither the U.S. Food and Drug Administration nor the Australian Therapeutic Goods Administration provides any regulatory oversight. He noted that prices for the testing vary, but he believes that there is no evidence that analgesia can be improved by acting on test results.

As an example, he noted that the company in Australia employs genetic predictors of CYP2D6 function, an enzyme important to opioid metabolism, to estimate benefit from this class of analgesics. However, published studies have not yet generated compelling evidence that this is clinically relevant for either improving pain control or avoiding adverse events.

In the case of oxycodone, studies comparing poor metabolizers to ultra-rapid metabolizers do show important differences in experimental models of pain, but “clinical studies have really shown no effect,” Dr. Somogyi said.

He drew the same conclusion about CYP2D6 function in regard to the effects of codeine and the variants in the OPRM1 gene and their effect on the Mu receptor and response to morphine. In all cases, there are studies to suggest genetic differences are meaningful in experimental models, but no evidence from a clinical study to show that acting on this information changes outcome or otherwise improves care.

Although he acknowledged that it is tempting to believe pharmacogenetics can explain the well-known variability in response to analgesics, “other factors are just swamping these pharmacogenetics variables,” Dr. Somogyi maintained. Not least of these other factors are the psychosocial factors that influence response to pain stimuli.

This does not preclude an eventual role for pharmacogenetics in the selection of analgesics. Dr. Somogyi, who has been working in this area for several decades, outlined a broad array of promising areas of research. It is the current clinical application of pharmacogenetics with which Dr. Somogyi took issue. He criticized many of the marketing claims made on behalf of available tests, which he considers unsubstantiated.

Deferring to the expertise of Dr. Somogyi, Dr. Paul A. Sloan, professor and vice chair for research, University of Kentucky, Lexington, said he found the perspective compelling. In an interview, Dr. Sloan, cochair of the 2015 ICOO meeting, reported that he knows of no one using pharmacogenetics testing to guide analgesic choice, and he reiterated Dr. Somogyi’s concerns about the need to validate the quality of tests as a part of an effort to confirm their viability as clinical tools.

Dr. Somogyi reported having no financial disclosures.

BOSTON – Many cancer patients do not pursue or at least do not achieve complete freedom from pain when permitted control over their opioid dose, according to a comprehensive analysis of published studies that evaluated patient-controlled analgesia.

“We do not know why. Patients were encouraged in these studies to titrate opioids until they were pain free or until they had side effects. Although this could be an issue of side effects, another interpretation is that complete pain control is not the goal for many individuals,” reported Dr. Brian H. Wetherington of the University of Kentucky, Lexington.

The data from this analysis were presented at the International Conference on Opioids from a comprehensive literature search that included 905 potentially relevant articles. Of these, 62 met inclusion criteria, particularly an assessment of patient-controlled opioids in patients with cancer pain. The studies also had to assess pain control with a visual analog scale (VAS) or the Neuropathy Pain Scale (NPS) using a 10-point system with 10 being the greatest level of pain imaginable.

“We were interested in evaluating whether patients, when given complete control over their opioids, would take sufficient doses to provide complete pain relief, which is often stated as the goal in pain management,” explained Dr. Wetherington, who was coauthor of a study led by his colleague at University of Kentucky, Dr. Michael Harned.

The answer was no. When the data from the 62 studies, which included 5,251 patients with cancer pain were collated, the average pain score at baseline was 5.4. At the time of assessment of pain control, the mean pain score was 2.7.

“The mean pain score for patients managing their own cancer pain on opioids was reduced from study entry but remained at the moderate to severe pain level or higher than what many health care providers would recommend,” Dr. Wetherington reported.

This review of published studies does not explain why lower pain scores are not reached, but the Dr. Wetherington and his coauthors hypothesized that patients are demonstrating their own benefit-to-risk ratio assessment.

This is thought to be the first systematic review to find that patients do not seek complete control of pain when given access to unrestricted analgesia, but several individual studies have made the same point. In one study cited by the authors, patients on a fentanyl patch only reduced their pain scores to 3.0 on average when given unlimited access to oral morphine for breakthroughs (J. Pain Symptom Manage. 1998;16:102-11).

“We think this deserves further study, because there may be lessons regarding how we think of optimal pain control. While the therapeutic target is often described as complete pain relief, these data suggest that this may not be the goal for patients when they are left to select their own level of pain control,” Dr. Wetherington explained.

The same observation regarding the failure of patients to eliminate all pain on patient-controlled analgesia has been made anecdotally by Dr. William G. Brose of Stanford (Calif.) University. However, he suggested in an interview that patients might be reluctant to rate themselves completely pain free on a subjective scale. He also believes that level of analgesia may not be the most relevant endpoint.

“We are increasingly evaluating change in patient function, which may be a more useful tool for evaluating the efficacy of pain control,” Dr. Brose said.

BOSTON – Many cancer patients do not pursue or at least do not achieve complete freedom from pain when permitted control over their opioid dose, according to a comprehensive analysis of published studies that evaluated patient-controlled analgesia.

“We do not know why. Patients were encouraged in these studies to titrate opioids until they were pain free or until they had side effects. Although this could be an issue of side effects, another interpretation is that complete pain control is not the goal for many individuals,” reported Dr. Brian H. Wetherington of the University of Kentucky, Lexington.

The data from this analysis were presented at the International Conference on Opioids from a comprehensive literature search that included 905 potentially relevant articles. Of these, 62 met inclusion criteria, particularly an assessment of patient-controlled opioids in patients with cancer pain. The studies also had to assess pain control with a visual analog scale (VAS) or the Neuropathy Pain Scale (NPS) using a 10-point system with 10 being the greatest level of pain imaginable.

“We were interested in evaluating whether patients, when given complete control over their opioids, would take sufficient doses to provide complete pain relief, which is often stated as the goal in pain management,” explained Dr. Wetherington, who was coauthor of a study led by his colleague at University of Kentucky, Dr. Michael Harned.

The answer was no. When the data from the 62 studies, which included 5,251 patients with cancer pain were collated, the average pain score at baseline was 5.4. At the time of assessment of pain control, the mean pain score was 2.7.

“The mean pain score for patients managing their own cancer pain on opioids was reduced from study entry but remained at the moderate to severe pain level or higher than what many health care providers would recommend,” Dr. Wetherington reported.

This review of published studies does not explain why lower pain scores are not reached, but the Dr. Wetherington and his coauthors hypothesized that patients are demonstrating their own benefit-to-risk ratio assessment.

This is thought to be the first systematic review to find that patients do not seek complete control of pain when given access to unrestricted analgesia, but several individual studies have made the same point. In one study cited by the authors, patients on a fentanyl patch only reduced their pain scores to 3.0 on average when given unlimited access to oral morphine for breakthroughs (J. Pain Symptom Manage. 1998;16:102-11).

“We think this deserves further study, because there may be lessons regarding how we think of optimal pain control. While the therapeutic target is often described as complete pain relief, these data suggest that this may not be the goal for patients when they are left to select their own level of pain control,” Dr. Wetherington explained.

The same observation regarding the failure of patients to eliminate all pain on patient-controlled analgesia has been made anecdotally by Dr. William G. Brose of Stanford (Calif.) University. However, he suggested in an interview that patients might be reluctant to rate themselves completely pain free on a subjective scale. He also believes that level of analgesia may not be the most relevant endpoint.

“We are increasingly evaluating change in patient function, which may be a more useful tool for evaluating the efficacy of pain control,” Dr. Brose said.

BOSTON – Many cancer patients do not pursue or at least do not achieve complete freedom from pain when permitted control over their opioid dose, according to a comprehensive analysis of published studies that evaluated patient-controlled analgesia.

“We do not know why. Patients were encouraged in these studies to titrate opioids until they were pain free or until they had side effects. Although this could be an issue of side effects, another interpretation is that complete pain control is not the goal for many individuals,” reported Dr. Brian H. Wetherington of the University of Kentucky, Lexington.

The data from this analysis were presented at the International Conference on Opioids from a comprehensive literature search that included 905 potentially relevant articles. Of these, 62 met inclusion criteria, particularly an assessment of patient-controlled opioids in patients with cancer pain. The studies also had to assess pain control with a visual analog scale (VAS) or the Neuropathy Pain Scale (NPS) using a 10-point system with 10 being the greatest level of pain imaginable.

“We were interested in evaluating whether patients, when given complete control over their opioids, would take sufficient doses to provide complete pain relief, which is often stated as the goal in pain management,” explained Dr. Wetherington, who was coauthor of a study led by his colleague at University of Kentucky, Dr. Michael Harned.

The answer was no. When the data from the 62 studies, which included 5,251 patients with cancer pain were collated, the average pain score at baseline was 5.4. At the time of assessment of pain control, the mean pain score was 2.7.

“The mean pain score for patients managing their own cancer pain on opioids was reduced from study entry but remained at the moderate to severe pain level or higher than what many health care providers would recommend,” Dr. Wetherington reported.

This review of published studies does not explain why lower pain scores are not reached, but the Dr. Wetherington and his coauthors hypothesized that patients are demonstrating their own benefit-to-risk ratio assessment.

This is thought to be the first systematic review to find that patients do not seek complete control of pain when given access to unrestricted analgesia, but several individual studies have made the same point. In one study cited by the authors, patients on a fentanyl patch only reduced their pain scores to 3.0 on average when given unlimited access to oral morphine for breakthroughs (J. Pain Symptom Manage. 1998;16:102-11).

“We think this deserves further study, because there may be lessons regarding how we think of optimal pain control. While the therapeutic target is often described as complete pain relief, these data suggest that this may not be the goal for patients when they are left to select their own level of pain control,” Dr. Wetherington explained.

The same observation regarding the failure of patients to eliminate all pain on patient-controlled analgesia has been made anecdotally by Dr. William G. Brose of Stanford (Calif.) University. However, he suggested in an interview that patients might be reluctant to rate themselves completely pain free on a subjective scale. He also believes that level of analgesia may not be the most relevant endpoint.

“We are increasingly evaluating change in patient function, which may be a more useful tool for evaluating the efficacy of pain control,” Dr. Brose said.