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Prescribing Opioids for Chronic Noncancer Pain
in Primary Care: Risk Assessment
Allan Gordon, MD1
Edward J. Cone, PhD2
Anne Z. DePriest, PharmD3
Robert A. Axford-Gatley,
MD4
Steven D. Passik, PhD5
1
Neurologist and Director,Wasser
Pain Management Centre, Mount
Sinai Hospital,Toronto, ON, Canada;
2
Associate Professor, Department of
Psychiatry and Behavioral Sciences,
Johns Hopkins School of Medicine,
Severna Park, MD; 3
Senior Scientist,
Healthcare Services, Aegis Sciences
Corporation, Nashville,TN; 4
Senior
Medical Director, C4 MedSolutions,
LLC,Yardley, PA; 5
Director of Clinical
Addiction Research and Education,
Millennium Laboratories, San Diego,
CA
Correspondence: Allan Gordon, MD,
FRCPC,
Mount Sinai Hospital Joseph and Wolf
Lebovic Health Complex,
600 University Avenue,
Toronto, ON,
Canada M5G 1X5.
Tel: 416-586-4800, ext. 5997
Fax: 416-586-5067
E-mail: allan.gordon@utoronto.ca
DOI: 10.3810/pgm.2014.09.2810
Abstract: The use of opioids for patients with chronic noncancer pain has increased dra-
matically, and with increasing use there is increasing concern about the potential for abuse and
addiction during long-term treatment. Clinicians should avoid viewing formal or subjective risk
assessment as a means of classifying patients into 2 distinct categories: compliant patients and
substance abusers. The provider who perceives a patient as compliant may have a complacent
attitude toward aberrant drug-related behavior, presuming that these signs reflect inadequately
controlled pain, to be addressed by dose escalation. The provider who perceives a patient as
a substance abuser may refuse to provide treatment for pain, leaving the patient to seek either
illicit drugs or prescribed treatment from another provider. In fact, in seemingly compliant
patients, any noncompliant use of opioids presents a safety risk regardless of the explanations
offered. Even in known or suspected drug abusers, chronic pain warrants the use of adequate
pharmacotherapy, although treatment in such cases may exclude drugs with high abuse poten-
tial. Thus, all aberrant drug-related behavior should be addressed within a treatment plan that
combines adequate pain care with suitable interventions for the aberrant behavior, following
current best practice strategies. This approach is consistent with the approach taken with other
health conditions, such as diabetes or hypertension, for which it is understood that noncompli-
ance with therapy presents a risk of harm.
Keywords: addiction; chronic noncancer pain; primary care; risk assessment; opioids; sub-
stance abuse
Introduction
Opioids are recommended for judicious use in carefully selected patients with moderate
to severe chronic noncancer pain.1
However, increased prescribing of opioids in recent
years has been accompanied by an increased frequency of abuse, addiction, overdose,
and death.2
Given that fewer than one third of all medical schools in the United States
and Canada provide instruction on the use of opioids in pain management,3,4
it is under-
standable that many prescribers lack confidence in their prescribing skills concerning
medications with potential for abuse.5,6
Pain and substance abuse are distinct but equally unavoidable concerns in medical
practice. In the clinical management of patients with chronic pain (particularly chronic
noncancer pain), simply opting out of pain management or opioid prescribing is not
an adequate response because professional ethics preclude withholding these medi-
cations from patients for whom their use is warranted. Medical ethics also preclude
prescribing drugs with abuse potential in the absence of adequate skills to manage the
risks associated with their use.
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Evidence-based strategies to minimize the risk of
substance abuse in opioid-treated patients are recommended
in clinical practice guidelines.7
Clinicians are advised to take
a thorough patient history and conduct a medical examination
before initiating opioid therapy to establish that the claim of
pain is legitimate and of an etiology that is likely to respond
to opioid analgesics.1,7–9
It is important to identify risk fac-
tors for abuse, most notably a personal or family history of
substance abuse or psychiatric illness.1,7,8
Risk assessment
tools are available for this purpose, such as the Opioid Risk
Tool,10
Current Opioid Misuse Measure,11
Screener and
OpioidAssessment for Patients with Pain–Revised Version,12
and Prescription Drug Use Questionnaire.13
Because misuse
of medications may occur even among patients assessed as
low risk, vigilant compliance monitoring (eg, pill counts,
urine toxicology testing) should be undertaken as a uni-
versal precaution in all patients receiving chronic opioid
therapy.1,7,8
Patients need to understand the goals of therapy
(eg, improved function rather than absence of pain), risks
associated with opioids, the need for compliance with therapy
and monitoring, and the potential effect of noncompliance
on the treatment plan; formalizing this understanding with
a signed controlled substance agreement is advisable.1,7,8
In
patients selected as suitable, opioid therapy may be initiated,
cautiously titrating to a dose that is tolerable and achieves
realistic therapeutic goals (eg, coping with activities of daily
living, returning to work).7,9
Prescribers should be attentive
to information from the patient’s pharmacist, other caregiv-
ers, and family members regarding potentially problematic
behavior7
and should participate in available compliance
monitoring systems, such as the Prescription Drug Monitor-
ing Programs (PDMPs), established in most US states14,15
and
several Canadian provinces.16
The thesis of this narrative review, aimed at primary
care clinicians, is that every caregiver has a responsibility
to recognize evidence of aberrant drug-related behavior in
patients under their care. This review provides perspectives
on the scope of the clinician’s responsibilities in the use of
opioids, the inevitability of risk of abuse and addiction, and
the pitfalls of inadequate knowledge, with illustrative case
histories.
Issues in Risk Assessment
Perceptions regarding the risk of addiction among patients
receiving opioid therapy for pain have evolved. The unin-
formed notion that any use of opioids is apt to lead to addic-
tion gave way to the perception that addiction occurs in only
a tiny minority of patients, as seen in a letter published in
1980 in the New England Journal of Medicine, reporting
that only 4 of 11 882 patients who received $ 1 opioid
dose during a hospitalization subsequently showed signs of
addiction.17
More recent data suggest that the at-risk popu-
lation is a considerably larger minority. In a recent review,
Manchikanti et al18
summarized 17 studies that determined
the prevalence of substance abuse among chronic pain
patients to be in the range of 18% to 41%. Although the
discrepancy may relate in part to the difference between
an estimated prevalence of addiction versus any misuse
including addiction, both estimates could lead some clinicians
into a complacent attitude about the risk of abuse in patients
receiving chronic opioid therapy.
The simplistic notion that risk assessment is aimed at
classifying patients into the mutually exclusive categories
of compliant patients versus drug abusers can lead to inap-
propriate responses to aberrant behavior: disregard of risk in
patients perceived as compliant or a refusal to treat patients
perceived as drug abusers. These poor practice patterns
persist not only because many prescribers have insufficient
knowledge about the risks and responsibilities attendant to
the use of opioids for chronic pain, but also because they
may not even be aware of their own insufficient knowledge
of the diverse causes of aberrant behavior and of abnormal
or unexpected findings on drug urine testing.19
One of the hazards of making glib assumptions about
patients receiving opioids is failure to distinguish aberrant
drug-related behavior from “pseudoaddiction,” which refers
to repeated requests for pain relief that are in fact justi-
fied by an inadequate therapeutic effect on the prescribed
regimen and that cease if adequate pain relief is obtained.20
The term pseudoaddiction was first applied to the case of a
hospitalized, 17-year-old leukemia patient with pneumonia,
whose responses to inadequate analgesia resembled opioid
addiction—frequent requests for opioids by specific name,
escalation of behaviors suggestive of addiction, and displays
of impatience and hostility.21
The authors who presented the
case commented that pseudoaddiction is a condition that
manifests with behaviors similar to those associated with
drug seeking, but represents a response to inadequate pain
control.21,22
Thus, the clinician observing requests for more
analgesics in a patient with chronic pain should consider the
possibility of pseudoaddiction in the differential diagnosis.
This does not justify dose escalation on demand, but may
prompt consideration of other options, and perhaps a review
of the original diagnosis. Patients in this situation may be
requesting more opioids for inadequate pain relief because
they are unaware that other therapeutic options exist.
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A wide array of noncompliant behaviors may reflect
opioid misuse, and the risk of misuse increases with the
number of such behaviors.23,24
In 1 study, the presence of any
of 4 aberrant opioid-related behaviors was associated with
an increased risk of substance abuse or dependence.23
In a
similar study, the presence of $ 4 aberrant behaviors was
associated with a 10-fold increase in the risk of substance
abuse.24
These behaviors include purposeful oversedation,
use of opioids for purposes other than pain relief, unauthor-
ized dose increases, and intoxication after taking opioids
(Table 1).23
Although a minority of patients represents the extremes in
opioiduse—thefullycompliantpatientwithnohistoryofaber-
rant drug-related behavior versus the addict—the challenge
of risk assessment lies in the great majority of patients in the
middle, for whom there appear to be mixed behaviors, some
demonstrating compliance and reliability but some indicative
of aberrant behavior. Clinicians who can accurately interpret
early signs of aberrant behavior may be able to prevent some
such situations from escalating into outright abuse.
Without such clinical acumen, clinicians cannot respond
appropriately to aberrant drug-related behavior. The result
may be a reflexive decision to refuse to initiate opioid therapy
or to terminate opioid treatment that has already started, or
it may be misinterpretation or disregard of the evidence.25,26
In the absence of adequate investigation into the causes of
the aberrant behavior, neither course of action represents
acceptable clinical practice. The next section presents real
case histories that provide cautionary lessons in how clini-
cians may respond adequately or inadequately to aberrant
drug-related behavior.
Case Studies
Aberrant or suspicious drug-related behavior must not be
ignored or automatically interpreted as evidence of addic-
tion or willful misuse; such cases must be carefully evalu-
ated to determine the cause. Evaluation requires more than
a reflexive response to the overall demeanor of the patient;
a deceitful patient may not match any stereotypical profile
of a substance abuser, and a patient who is responding to
inadequately treated pain may be mistaken for an abuser.
The following case histories present a selection of scenarios
showing the importance of accurate evaluation. All derive
from a single urban primary care practice in Ontario, Canada,
between 1998 and 2007.
A Patient Showing Strong Evidence of
Abuse
A 24-year-old woman presented to her family physician
(FP) with an unexplained exacerbation of chronic left
knee pain attributed to a motor vehicle accident 10 years
earlier, treated by surgical repair of the anterior cruciate
ligament. She demanded specific brand names of oxycodone/
acetaminophen and diazepam, explaining that these agents
were prescribed following the surgery.
History of Present Illness
In the 4 years that the patient had been seeing the FP, she
had occasionally complained of knee pain following stress
(eg, carrying groceries), which usually resolved with rest,
ice, and nonprescription nonsteroidal anti-inflammatory
drugs (NSAIDs).
Past Medical/Social History
The patient was the mother of 2 preschool children; she
and her husband of 3 years were artists but lived mainly on
public assistance. Raised in foster care, she became addicted
to heroin in her early teens, but had been sober for 4 years
Table 1. Aberrant Drug-Related Behaviors Indicative of Opioid
Misuse
Altering route of delivery
• Injecting, biting, or crushing oral formulations
Accessing opioids from other sources
• Taking the drug from friends or relatives
• Purchasing the drug on the “street”
• Double-doctoring
Unsanctioned use
• Multiple unauthorized dose escalations
• Binge rather than scheduled use
Drug seeking
• Recurrent prescription losses
• Aggressive complaining about the need for higher doses
• Harassing staff for faxed scripts or fit-in appointments
• Nothing else “works”
Repeated withdrawal symptoms
• Marked dysphoria, myalgias, gastrointestinal symptoms, craving
Accompanying conditions
• Currently addicted to alcohol, cocaine, cannabis, or other drugs
• Underlying mood or anxiety disorders not responsive to treatment
Social features
• Deteriorating or poor social function
• Concern expressed by family members
Views on the opioid medication
• Sometimes acknowledges being addicted
• Strong resistance to tapering or switching opioids
• May admit to mood-leveling effect
• May acknowledge distressing withdrawal symptoms
Reproduced with permission from Canadian guideline for safe and effective use
of opioids for chronic non-cancer pain. National Opioid Use Guideline Group
(NOUGG). http://nationalpaincentre.mcmaster.ca/opioid/.Accessed September 18,
2013.8
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following a year-long residential drug rehabilitation program,
and she continued to participate in Narcotics Anonymous
with her husband, who was also a recovering addict.
Physical Examination
Scarring and chronic limited range of motion of the left
knee showed no change, no instability, and no swelling. The
patient had uncharacteristically poor hygiene and displayed
unusually abrupt and irritable behavior.
Impression
Drug seeking.
Plan
The FP refused to prescribe opioids because of the patient’s
history of addiction, but instead offered NSAIDs, referral
back to the surgeon (scheduled in 8 weeks), and referral to
a psychiatrist specializing in pain and addiction (scheduled
in 6 weeks).
Follow-Up
The patient never returned to the FP, who began receiving
reports from emergency departments and after-hours clinics
that the patient presented claiming she was prescribed
oxycodone/acetaminophen and diazepam by her FP, but
needed more because she had run out, lost her prescription,
or thedosewasinadequate.Someprovidersfulfilledherrequests
and some refused, but none attempted to make contact with
the FP or the patient’s pharmacist before deciding whether
to prescribe. The FP received a note from the psychiatrist
2 weeks after his consult (8 weeks after referral) stating that
the patient had been seeking drugs for abuse and that she
had refused admission to a 21-day residential rehabilita-
tion program. The FP received a note from the orthopedic
surgeon 2 weeks after his consult (10 weeks after referral),
indicating that he had diagnosed posttraumatic arthritis, for
which he administered an intra-articular steroid injection and
provided a 1-month supply of oxycodone/acetaminophen
and diazepam, increasing the dose she claimed to have
been prescribed by the FP. The surgeon did not attempt to
make contact with the FP or the patient’s pharmacist before
prescribing. A few days before the surgeon’s consult note
arrived, the FP received word that the patient had been
found dead in her home of a presumed overdose. She had
been living alone since her husband left a few weeks before
because of her substance abuse, taking the children with him
for their safety. The husband attributed her relapse to her
continued association with active substance abusers.
Analysis of Case
In response to concerns about prescription drug abuse, some
clinicians may try to avoid the problem; they avoid prescrib-
ing drugs with abuse potential, avoid treating patients with
an addiction history, and avoid treating chronic pain. For this
patient, simply refusing to prescribe medications with abuse
potential was an inadequate solution to her substance abuse
problem. Referral to more qualified caregivers was appropri-
ate, but the delay in accessing this care was substantial. In
hindsight, the FP realized he had information and resources
that could have been applied more effectively.
TheFPwasawarethatthispatienthadahistoryofaddiction,
but he had not been inquiring about relapse risk factors, such as
emotionalstress,orprovidingguidancetoavoidrelapse,suchas
the need to stop associating with active substance abusers. He
realized also that he could have avoided delay in treatment by
offering the patient access to the same rehabilitation program
recommendedbythepsychiatrist,andthathecouldhavespoken
with her husband to gain his assistance and the support of their
Narcotics Anonymous group in addressing her relapse.
A Patient With Objectively Low Risk of
Substance Abuse
A63-year-old woman presented as a new patient with chronic
osteoarthritis pain in both knees. Her previous FP, Dr. A.,
who had recently died, had managed her chronic pain for
the previous 2 years with oxycodone controlled release (CR)
80 mg twice daily. She had a copy of her chart from Dr. A.
and an empty pill bottle, with the label indicating that she
should have run out of medication 2 days previously.
The patient claimed she had been prescribed opioids for her
osteoarthritisfor . 10years,afterexperiencinggastrointestinal
bleedingwithNSAIDs.Shehadnoothermedicalproblemsand
took no other medications. She denied any history of substance
abuse. The patient lived with her 40-year-old son and his wife
and children; the family received public assistance.
This pleasant, well-groomed patient’s physical exam was
unremarkable except for mild bilateral crepitus, effusion,
and varus deformity in the knees, consistent with mild to
moderate osteoarthritis.
Impression
Mild to moderate osteoarthritis of both knees; objectively
considered to be low risk for substance abuse.
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Plan
The FP explained what a controlled-substance contract is
and that it would require the patient to obtain all opioid pre-
scriptions from a single doctor and comply with regular pill
counts and urine drug screening. The FP said her acceptance
as a new patient was provisional on his review of Dr. A.’s
chart and contacting her pharmacist and previous health care
providers. She left with requisitions for a urine drug test and
knee radiographs, expressing disappointment that the FPdid
not fulfill her request for oxycodone CR at this visit.
Follow-Up
Review of her chart showed no record of risk screening,
controlled-substance contract, urine testing, or radiographs.
No PDMPexisted in this location at the time of this case, but
the FP routinely contacted local pharmacists for information
on patient history of prescription medication use. A phone
call to the pharmacist who filled the patient’s last prescrip-
tion revealed she had always received the same dose and
quantity of oxycodone CR from Dr. A.; there was no his-
tory of early fills, lost prescriptions, or opioid prescriptions
from other prescribers. However, phone calls by the FP to
several other nearby pharmacies revealed that the patient
had been regularly filling prescriptions for hydromorphone
in the extended-release form, morphine extended release,
and fentanyl patch—each prescribed by a different physi-
cian and filled at a different pharmacy, with no evidence of
irregularities. In all, she had been obtaining narcotics with a
street value of more than $5000 per month, paid for by public
assistance medical coverage.
Confidentiality laws prohibited the FPfrom contacting the
police, but he was legally required to contact the Provincial
Drug Formulary, whose representative explained that their
protocol for monitoring prescriptions would generate alerts
about early fills or multiple doctors prescribing the same
opioid, but different opioids prescribed by different doctors
would not be recognized as an anomaly.
The FP phoned the patient to inform her he would not be
accepting her into his practice. He received no further contact
from the Provincial Drug Formulary or law enforcement, but
later learned that this patient’s son had a criminal history
involving gangs and drugs.
Analysis of Case
This case illustrates the limitations of risk assessment, the
need for a universal precautions approach to compliance
monitoring, and the value of communication with other
care providers (eg, pharmacists).7,27
Currently, PDMPs in
the United States and Canada are intended to identify the
behavior described above,14,16,28
but some prescribers do not
use these programs.15,29
A Patient Under Extreme Emotional Stress
A tearful, distraught 44-year-old woman with a well-
documented history of complex regional pain syndrome
(CRPS) presented to her FP with a 48-hour history of
excruciating pain in her right arm from shoulder to finger-
tips. She routinely took oxycodone CR 40 mg twice daily
and amitriptyline 50 mg once daily, but she had consumed
a week’s supply of oxycodone CR over the past 48 hours.
She requested a prescription for oxycodone in the immediate-
release form to relieve the acute pain.
Brief History
The patient described the pain as a heightened intensity of
the same chronic symptoms she had experienced from CRPS
in the affected area since experiencing a work-related scald
injury 5 years earlier. She believed the pain was exacerbated
by the physical strain of moving her belongings out of her
boyfriend’s home after a quarrel 2 days ago.
Patient had a chaotic childhood, including sexual abuse, aban-
donment, and foster care. This was the fourth relationship
breakup she recounted since first seeing the FP 18 months
ago. Each breakup was associated with a physical event
causing an exacerbation of her CRPS (a slip on an icy side-
walk, a fall on the stairs, physical abuse), for which she had
requested additional opioids. The patient was a single mother
of 4 children, all of whom were in foster care. She lived on
workers’ compensation insurance from her accident.
Unchanged scarring of the dorsum of the right hand and
forearm; chronic wasting of the muscles of the right hand,
forearm, and upper arm; inability to fully close right hand or
extend elbow; right arm cooler and paler than left; burning
pain on light touch of hand or forearm.
Impression
Unchanged CRPS; misuse of opioids for emotional
distress.
Plan
The FP refused the patient’s request for opioids; he sug-
gested that she contact her pain specialist and referred her to
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a psychiatrist to establish a diagnosis and a plan for long-term
treatment.
Follow-Up
Upon being denied her request for oxycodone immediate
release, the patient became very angry and uttered threats
against the FPand his staff. This behavior was not unusual for
this patient, and the FP had come to regard such statements as
hyperbole. However, she did meet with the psychiatrist, who
diagnosedherwithborderlinepersonalitydisorderandreferred
toaspecialtyclinicfordialecticalbehavioraltherapy(atherapy
specific to borderline personality disorder).30
Analysis
Although the FP had taken a full history, formal risk assess-
ment had not been performed. Administration of the Opioid
Risk Tool would have placed her in the “moderate” risk cat-
egory based on her history of substance abuse, sexual abuse,
and psychiatric illness.10
This would not have precluded her
being prescribed an opioid for a legitimate pain indication;
however, it would have alerted the treating physician of the
need for heightened monitoring and avoidance of opioid
formulations with high abuse potential.
This case illustrates “chemical coping”: misuse of pain
medication to deal with depression, anxiety, anger, or stress.
This patient repeatedly used opioids prescribed for pain to
deal with the emotional stress of broken personal relation-
ships. Clinicians should be alert to the possibility of chemical
coping in patients who describe a sense of disconnection
from their own feelings; unable to process or alleviate their
feelings, they may experience psychological problems as
somatic symptoms for which they seek pharmacotherapy.31,32
In addition, certain psychiatric conditions are associated with
aberrant drug-related behavior,33,34
including borderline per-
sonality disorder.35
Although it may be difficult to distinguish
between chemical coping and recreational use or addiction,
the 38-item Chemical Coping Index developed by Kirsh and
colleagues31
may be useful for this purpose.
Conclusion
All of the cases presented here illustrate the potential pitfalls
of an inadequate clinical response to the intrinsic risks asso-
ciated with opioid therapy for chronic noncancer pain. They
also reveal that risk evaluation involves more than classifica-
tion as either compliant patients or drug abusers and addicts.
Some patients occupy a middle ground wherein they have a
legitimate pain complaint but also exhibit aberrant behaviors
that must be recognized and addressed appropriately to avoid
harm and provide optimal care.
Concerns about the potential for abuse and addiction
have left many physicians reluctant to prescribe opioids.
However, a refusal to provide adequate treatment for chronic
pain may leave these patients to seek help from other health
care providers unfamiliar with the patient’s history or from
illicit sources.
Assessing aberrant drug-related behavior is a challeng-
ing responsibility, but it also presents an opportunity to
intervene before such behaviors escalate into outright abuse.
Given the present widespread abuse of prescription drugs,
all health care providers should be vigilant to signs of aber-
rant behavior and should be able to evaluate it and respond
appropriately. Prescription drug abuse can be curbed only
when prescribers consistently adhere to evidence-based and
expert-recommended best practices to assess risk, to prescribe
responsibly, and to recognize and respond appropriately to
aberrant drug-related behavior.
Evidence-based guidelines to mitigate the risks asso-
ciated with chronic opioid therapy8,36,37
reflect 5 main
principles9
: 1) Adequate patient assessment, including
abuse risk assessment, using validated screening tools
and symptom assessment; 2) Appropriate treatment of
the underlying painful condition and comorbidities that
may exacerbate pain; 3) Classification of the pain type
(eg, nociceptive vs neuropathic, cancer vs noncancer)
and assessment of its chronicity, severity, and effect on
the patient’s life; 4) Use of adjunctive nonpharmacologic
modalities as appropriate; and 5) Encouraging patient
self-management and responsibility and providing patient
education. However, it must be acknowledged that even
with adherence to best practices, misuse of prescribed
opioids can occur because physicians can influence but
not control their patients’ actions.
Acknowledgments
The authors contributed to the literature search design; the
analysis and interpretation of the literature reviewed in this
manuscript; and to the preparation, review, and final approval
to submit the manuscript, independent of the funding orga-
nization (Endo Pharmaceuticals Inc., Malvern, PA). The
authors wish to acknowledge the helpful direction and review
of early drafts provided by Douglas L. Gourlay, MD, of the
Centre for Addiction and Mental Health, Toronto, Ontario,
Canada, and by Howard A. Heit, MD, of Georgetown
University, Washington, DC. Editorial assistance was
provided by Steven Tiger, PA, BS, of Complete Healthcare
Communications, Inc. (Chadds Ford, PA) and was funded
by Endo Pharmaceuticals Inc.
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Conflict of Interest Statement
Allan Gordon, MD, has received research funding and acted
as a consultant, adviser, and/or speaker for CIHR, CFI, Pfizer,
Purdue, Lilly, Boehringer, Merck, AstraZenca, Janssen,
Paladin, Biovail, and Wyeth. Edward J. Cone, PhD, discloses
a conflict of interest with Aegis Sciences Corporation. Anne
Z. DePriest, PharmD, is an employee of Aegis Sciences
Corporation. Robert Axford-Gatley, MD, is an employee
of C4 MedSolutions, LLC (Yardley, PA), a CHC Group
company. Steven D. Passik, PhD, has received honoraria
related to speakers’ bureau activities from Ameritox, Ltd.,
Cephalon, Inc., Covidien, Endo Pharmaceuticals, Janssen
Pharmaceuticals, Inc., Millennium Pharmaceuticals, Inc.,
Purdue Pharma L.P., PharmacoFore, Pfizer Inc., and Quest
Pharmaceuticals, Inc. He has received grant support related
to research activities from Covidien.
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