If you don't remember your password, you can reset it by entering your email address and clicking the Reset Password button. You will then receive an email that contains a secure link for resetting your password
If the address matches a valid account an email will be sent to __email__ with instructions for resetting your password
Although its inclusion in medical research is relatively recent and its interpretation is often variable, quality of life is increasingly being recognized as one of the most important parameters to be measured in the evaluation of medical therapies, including those for pain management. Pain, when it is not effectively treated and relieved, has a detrimental effect on all aspects of quality of life. This negative impact has been found to span every age and every type and source of pain in which it has been studied. Effective analgesic therapy has been shown to improve quality of life by relieving pain. Opioid analgesics, cyclooxygenase (COX)-2 inhibitors (or coxibs), and several adjuvant analgesics for neuropathic pain have been demonstrated to significantly improve quality-of-life scores in patients with pain. Coxibs provide effective, well-tolerated analgesia without some of the issues faced with opioids—benefits that should translate into improved quality of life. Recent studies have demonstrated that the COX-2 inhibitor rofecoxib significantly improves quality of life in patients with osteoarthritis and chronic, lower back pain. Quality-of-life measurements, especially symptom distress scales, can also be used as sensitive means of differentiating one agent from another in the same class. In future pharmacotherapeutic research, quality of life should be included as an outcome domain as are the traditionally measured variables of efficacy and safety. In particular, future studies of coxibs should include symptom distress scores as important quality-of-life measurements, to identify meaningful differences between this new class of analgesics and nonselective nonsteroidal anti-inflammatory drugs.
Pain is not only a highly noxious experience per se, but it can also have an overwhelmingly negative effect on nearly every other aspect of life, including mood and capacity to function in daily roles. According to a study by the World Health Organization, individuals who live with persistent pain are four times more likely than those without pain to suffer from depression or anxiety, and more than twice as likely to have difficulty working.
Pain is one of the most significant healthcare crises in the United States. Nearly half of Americans see a physician with a primary complaint of pain each year,
MayoClinic.com. Managing pain: attitude, medication and therapy are keys to control. Mayo Clinic Web Site. June 21, 2001. Available at: http://www. mayoclinic.com/invoke.cfm?id=HQ01055. Accessed September 19, 2001.
Even this fact belies the true magnitude of the problem, since a substantial number of people with pain do not consult a physician. In one of the largest survey studies on the subject of pain, 18% of respondents who rated their pain as severe or unbearable had not visited any healthcare professional, because they did not think that anyone could relieve their suffering.
The costs associated with pain are extremely high, both to the healthcare system and to society at large. Not only do individuals with pain have a greater rate of utilization of the healthcare system, but their productivity is substantially diminished. It has been estimated that more than 4 billion workdays are lost to pain annually. If one assumes a very conservative median US income of $23,000, then pain costs society $55 billion in lost productivity for full-time workers alone.
While these costs are enormous, one of the greatest tolls exacted by pain is on quality of life. Pain is widely accepted to be one of the most important determinants of quality of life, which can be defined as an individual's ability to perform a range of roles in society and to reach an acceptable level of satisfaction from functioning in those roles.
However, quality-of-life research is, relatively speaking, in its infancy, and the effect of symptoms such as pain on quality of life is just beginning to be understood.
Increasingly, however, quality of life is coming to be accepted as one of the most important outcome domains to be measured in the evaluation of any therapy or health-related intervention.
Quality of life is a more subtle indicator than the typically measured variables of efficacy and safety, but it is arguably more indicative of treatment value and may be more relevant to both patient satisfaction and willingness to adhere to treatment.
Measuring Quality of Life: The Scales and Beyond
Quality of life can be measured in a wide variety of ways, and an array of instruments has been developed to evaluate and attempt to quantify it. Several questions need to be answered to select the optimal instrument for any given circumstance.
In the present context, it is assumed that we are referring to health-related quality of life, which is more specific than general quality of life.
Which Is More Applicable, a Disease-Specific or a Generic Instrument?
Specific instruments are designed to measure quality of life in a particular disease state, such as cancer or arthritis. Numerous specific instruments are available in nearly every disease category; for example, there are at least four instruments that are specific to prostate cancer alone. The disadvantage of specific instruments is that their use makes it impossible to compare findings across disease states. Generic instruments are intended to measure quality of life in any disease state and across disease states as well. Their advantage is that they allow for groups of patients with various conditions to be compared with one another. Their disadvantage, however, is that because they involve many different types of constructs, and are so general, they are often not very effective at measuring improvement in a specific disease state as a consequence of an intervention. Thus, they may not pick up subtle but important shifts in quality of life resulting from a given treatment.
The classic example of a generic quality of life instrument is the Medical Outcomes Study Short Form 36, or SF-36.
The SF-36 is a 36-item survey of general health status that was designed to combine the comprehensiveness of much longer surveys with the brevity of relatively coarse single-item surveys. It can be self-completed, administered by computer, or conducted by a trained interviewer in person or over the telephone.
What Dimensions of Quality of Life Need to Be Measured?
Quality of life is inherently a multidimensional phenomenon, and most useful quality-of-life instruments reflect this. There are domain-specific quality-of-life instruments, which measure a single aspect of quality of life, such as physical function or anxiety. However, multidomain instruments are generally preferred, since an instrument that does not include several dimensions will make it impossible to determine the nature of a score change.
most acceptable quality-of-life assessment strategies address several or all of the following domains: physical, psychological, social, somatic, and spiritual.
Responder burden refers to the amount of effort that the patient must extend to complete the evaluation. The number of instruments, the number of questions in the instruments, and the conceptual difficulty of the response task must be considered. This is particularly important when measuring quality of life for patients in pain, because of the debilitating nature of the condition. While some patients are grateful for the caring and concern implied by the effort to solicit their feelings about their quality of life, others may be too incapacitated to fully comply. Less-than-full compliance can lead to inaccurate results.
What Are the Administrative Issues That Need to Be Considered?
Most quality of life evaluations require measurement at a minimum of two intervals—the baseline and then at a later point, typically after some form of treatment has been administered. Therefore, arrangements need to be made to ensure that the greatest possible number of patients complete follow-up evaluations. In addition, decisions need to be made about whether patients must complete their own evaluations (which may be difficult for patients who suffer from severe pain) or whether proxy completion will be permitted. It is generally agreed that self-report data are preferred because they decrease the possibility that proxies may unwittingly bias the results by allowing their own feelings and opinions related to quality of life to be reflected in their responses. Instruments written at low-literacy levels or in multiple languages can help decrease the need for proxy involvement, as can allowing the option of audiotaped or computerized questionnaire completion, particularly for patients whose movement is limited by severe pain.
Has the Instrument Proven to Be Both Valid And Reliable?
Validity and reliability are crucial characteristics of a useful quality-of-life questionnaire. A valid instrument is one that actually measures what it is intended to measure, whereas a reliable questionnaire is one that provides a reproducible result. A questionnaire administered on Day 1 and repeated a few days later should produce a nearly identical score, provided that no new variables have been introduced in the interim.
New approaches to the field of quality-of-life research add to the usefulness and interpretability of quality-of-life questionnaires. The Symptom Distress Inventory method, for example, involves providing patients with a checklist that allows them to indicate which disease-specific symptoms they have and how much distress each symptom produces. The magnitude of symptom distress has been found to be strongly correlated with traditional quality-of-life assessment tools and may in some cases be the most sensitive way to address health-related quality of life.
Furthermore, symptom distress methods have been shown to be more sensitive than traditional quality-of-life instruments in differentiating the impact of various drugs on quality of life.
Thus, when two drugs have equivalent efficacy but different side effect profiles (a common situation), these distinctions in side effects, picked up most sensitively by the symptom distress method, may underlie important differences in quality of life for those on the medications.
Utility methods enable the evaluation of treatment-related factors that affect quality of life (e.g., degree of pain relief or propensity to cause a side effect such as nausea) in the context of patient preferences. For example, patients may be asked to weigh the relative importance of various symptoms or other health-related factors (e.g., cost of treatment, life prolongation). Different treatments are then compared according to improvement in overall utility, rather than using a simple unidimensional outcome variable. Finally, calibration methods allow changes in quality of life to be evaluated comparatively against other stressful life events (e.g., job loss), thereby providing a comparative gauge of what magnitude of change on a quality of life (or symptom distress) scale is significant.
The Impact of Uncontrolled Pain on Quality of Life
Pain and quality of life are phenomena that share several fundamental characteristics. Pain has been defined by the American Pain Society as “an unpleasant sensory and emotional experience associated with actual or potential tissue damage.” Similarly, the Joint Commission on Accreditation of Healthcare Organizations notes that pain is a common experience that has adverse physiological and psychological effects when unrelieved.
Joint Commission on Accreditation of Healthcare Organizations
Assessment of persons with pain. Pain Assessment and Management An Organizational Approach. Joint Commission on Accreditation of Healthcare Organizations;,
Oakbrook Terrace, IL2000: 13-25
Hence, pain involves cognitive, motivational, affective, behavioral, and physical components. Quality of life, a construct that incorporates all factors that impact on an individual's life, has a similar all-encompassing nature.
Indeed, the World Health Organization's list of the domains and facets that comprise quality of life confirms the all-embracing nature of the concept (Table 1).
Pain, when it is ongoing and uncontrolled, has a detrimental, deteriorative effect on virtually every aspect of a patient's life. It produces anxiety and emotional distress; undermines well-being; interferes with functional capacity; and hinders the ability to fulfill family, social, and vocational roles. With such broad-based effects, it is apparent that pain would have the effect of diminishing quality of life.
The deteriorative effect on quality of life is universal; it spans every age and stage of life and occurs regardless of the pain's type or source. For example, in a study of 49,971 elderly nursing home residents with disorders of nearly every kind, Won and colleagues found that more than one in four (26.3%) experienced pain on a daily basis.
A strong association was found between daily pain and indices of poor quality of life: Patients who suffered from daily pain were more likely to have impairment in activities of daily living (odds ratio [OR]: 2.47), mood disorders (OR: 1.66), and decreased involvement in activities (OR: 1.35). These associations persisted even after the investigators adjusted for the potentially confounding effects of age, gender, race, cognitive status, and such debilitating conditions as arthritis, stroke, congestive heart failure, and Parkinson's disease.
The younger end of the age spectrum is equally vulnerable to the detrimental effects of pain on quality of life. In a study of 128 adolescents with chronic pain, Hunfeld and researchers found that quality of life decreased as intensity and frequency of pain increased.
The domains of psychological functioning (including feeling less at ease), physical status (including an increase in incidence of other somatic complaints), and functional status (defined as greater impediments to leisure and daily activities) were particularly affected. Notably, surveys of the patients' mothers revealed that the adolescents' pain reduced their families' quality of life as well.
The damaging effects of pain on quality of life have been demonstrated for nearly every kind of pain, including neuropathic pain, other chronic nonmalignant pain such as that associated with arthritis, and malignant pain.
For example, in a study of 150 patients with chronic pain, including pain of neuropathic, somatic, psychogenic, and visceral origins, Becker and colleagues found that scores on both the Psychological General Well-Being (PGWB) scale and the SF-36 were significantly reduced compared with scores in the normal population (P < 0.001).
(The PGWB is a 22-item instrument designed to measure subjective psychological well-being in population-based studies. It includes six parameters: anxiety, depression, vitality, positive well-being, self-control, and general health.
All eight SF-36 subscores, including bodily pain, general health, mental health, physical functioning, role-emotional, role-physical, social functioning, and vitality were significantly reduced compared with subscores for individuals without pain (Figure 1).
Furthermore, 40% of patients with pain had scores on the Hospital Anxiety and Depression scale that indicated the presence of a depressive disorder, whereas 50% had scores indicating a comorbid anxiety disorder.
Fig. 1Effect of chronic nonmalignant pain on quality of life, as indicated by SF-36 subscores, mean (SD) (n =150).19 • = population norm values; PF = physical functioning; RP = role-physical; BP = bodily pain; GH = general health; VT = vitality; SF = social functioning; RE = role-emotional; MH = mental health. *P < 0.001. Adapted with permission from Ref. 19.
The impact of malignant pain on quality of life is similarly severe. Rummans and coworkers studied the effect of pain on quality of life in 117 patients with recurrent breast or gynecological cancer.
The investigators found a substantial correlation between the presence of pain and the physical and social dimensions of quality of life. To their surprise, however, they found a weaker correlation between pain and the psychiatric and spiritual quality-of-life domains. They attributed this aberrant finding to the fact that the majority of these patients were experiencing mild to moderate pain and none were experiencing severe, incapacitating pain.
The majority of studies have demonstrated that there is a dose-response relationship between pain and quality of life: as one increases, the other proportionately decreases.
For example, in their study of 216 adults with various forms of cancer grouped by level of pain severity, Wang and colleagues found that those with moderate or severe pain had consistently lower SF-36 scores than patients with no pain or mild pain (Figure 2).
All mean Mental and Physical Component Summary scores declined as pain severity increased (P < 0.001 for both), and this relationship was found to exist independent of Eastern Cooperative Oncology Group (ECOG) performance status.
Fig. 2Mean SF-36 subscale scores shown by pain severity level.8 PF = physical functioning; RP = role limitations due to physical problems; BP = bodily pain; GH = general health perception; VT = vitality; SF = social functioning; RE = role limitations due to emotional problems; MH = mental health. Adapted with permission from Ref. 8.
“Many adults, including cancer patients, function quite effectively with background levels of pain which, for the most part, are not attended to. As pain increases, however, it passes a threshold beyond which it can no longer be ignored. At this point, it becomes disruptive to many aspects of the person's life.” According to their model, a progressively greater number of quality-of-life domains are impacted as pain becomes progressively worse (Table 2).
The direct and unambiguous association that exists between pain and quality of life would seem to highlight the importance of treating and effectively relieving pain. Unfortunately, the evidence overwhelmingly demonstrates that despite the availability of effective analgesic pharmacotherapy, pain is often undertreated and poorly controlled.
The inadequacy of current efforts at pain control, which is widely acknowledged by physicians, is perhaps particularly striking in the field of oncology. In the aforementioned study of cancer patients conducted by Wang and colleagues, 59% of patients who received treatment for pain had a negative Pain Management Index, meaning that their analgesic treatment did not meet the minimum standards of the World Health Organization guidelines.
Similarly, in a study supported by ECOG, the National Cancer Institute, the National Institutes of Health, and the Department of Health and Human Services, Cleeland and colleagues asked a group of 1308 outpatients with metastatic cancer from 54 ECOG-affiliated locations to rate the severity of their cancer pain during the preceding week, the degree of pain-related functional impairment they experienced, and the degree of relief provided by their analgesic regimens.
Of the group, 871 of 1308 (67%) reported that they had experienced pain or taken analgesics in the week preceding the study, and 475 of 1306 (36%) said that their pain was severe enough that it impaired their ability to function. Of the 597 patients for whom complete information was available, 250 (42%) received inadequate analgesia. Factors associated with poor pain management included minority race/ethnicity; greater discrepancy between patient and physician in judging degree of pain interference with activity; and pain unrelated to cancer, older age, female sex, and better ECOG performance status (i.e., physician's judgment that the patient was relatively less ill).
When queried, physicians admit that their efforts at pain management are largely inadequate. In a survey of all ECOG-affiliated physicians with pain management responsibility, Von Roenn and coworkers found that only 51% believed that pain control in their own practice settings was good or very good; 31% described it as fair, and 18% said that it was poor or very poor.
Effective Pain Control: Its Salutary Effect on Quality of Life
If poorly controlled pain has a deteriorative effect on quality of life, then the implication is that analgesics, by decreasing pain, will increase quality of life. Several recent studies have demonstrated that this intuitive association is true.
Katz N, Davis MW, Dworkin R. Topical lidocaine patch produces a significant improvement in mean pain scores in treated PHN patients: results of a multicenter open-label trial. In: Posters of the 20th Annual Scientific Meeting of the American Pain Society; Phoenix, AZ; April 19–22, 2001; Poster 741.
For example, our group measured changes in Brief Pain Inventory scores in 332 patients with postherpetic neuralgia treated with a 5% lidocaine patch for 28 days.
Katz N, Davis MW, Dworkin R. Topical lidocaine patch produces a significant improvement in mean pain scores in treated PHN patients: results of a multicenter open-label trial. In: Posters of the 20th Annual Scientific Meeting of the American Pain Society; Phoenix, AZ; April 19–22, 2001; Poster 741.
Katz N, Davis MW, Dworkin R. Topical lidocaine patch produces a significant improvement in mean pain scores in treated PHN patients: results of a multicenter open-label trial. In: Posters of the 20th Annual Scientific Meeting of the American Pain Society; Phoenix, AZ; April 19–22, 2001; Poster 741.
Rowbotham and colleagues had similar results in their study of 229 patients with postherpetic neuralgia who were randomized to receive gabapentin or placebo for four weeks.
At the conclusion of the study, average daily pain scores were reduced from 6.3 to 4.2 points in the gabapentin-treated patients, compared with a change from 6.5 to 6.0 points in the placebo group (P < 0.001). Simultaneously, SF-36 measures relating to physical functioning, role-physical, bodily pain, vitality, and mental health were all significantly better in the gabapentin group than in the placebo group (P ≤ 0.01). Gabapentin-treated patients also had significantly greater improvements than patients in the placebo group in Profile of Mood States assessments of depression-dejection, anger-hostility, fatigue-inertia, confusion-bewilderment, and total mood disturbance (P ≤ 0.01).
Fig. 3Effect of analgesic therapy with lidocaine patch 5% on quality-of-life indicators in patients with postherpetic neuralgia.26 BPI = Brief Pain Inventory. Adapted with permission from Ref. 26.
The link between new treatments for arthritis and patient quality of life has also been evaluated. Ehrich and coworkers recently reported the effect of a cyclooxygenase-2-selective inhibitor, rofecoxib, on health-related quality of life in 672 patients with osteoarthritis of the knee or hip.
Patients were randomized to receive once-daily placebo or rofecoxib at doses of 5, 12.5, 25, or 50 mg, and the SF-36 was administered at baseline and at the conclusion of week 6 of treatment.
All doses of rofecoxib were significantly superior to placebo in relieving arthritis pain. This improvement in arthritis symptoms was found to correlate directly with improvements in quality of life. Adjusted within-group mean change scores demonstrated that all doses of rofecoxib brought about significant improvement on both the mental and physical component summary scores (Figure 4),
as well as on all eight physical and mental health domains of the SF-36. These improvements were significantly greater (P < 0.05) than those obtained with placebo in all domains except general health. A dose-response relationship was noted, such that the mean changes in quality of life for the 12.5-, 25-, and 50-mg groups were of a larger magnitude than that for the 5-mg group.
The investigators hypothesized that the improvement in overall emotional well-being experienced by the rofecoxib-treated patients was probably due to increased ability to perform and enjoy routine tasks and leisure activities as a result of relief of osteoarthritis signs and symptoms.
Fig. 4Mean change from baseline in SF-36 component summary scores after Week 6 of treatment with rofecoxib in patients with hip or knee osteoarthritis (n = 672).7 Error bars represent 95% confidence intervals. PCS = physical component summary; MCS = mental component summary. Adapted with permission from Ref. 7.
Quality of Life as a Differentiator: When Efficacy Is Similar, Can Quality-of-Life Measures Be Used to Show the Superiority of One Medication Over Another?
Quality of life is clearly an important variable to measure in and of itself. However, another use for quality-of-life measurement is increasingly being recognized. In any therapeutic area, drugs within the same pharmacologic class often have similar efficacy profiles. In such cases, quality of life and other such indicators have been used successfully to differentiate one agent from another.
At least two studies have made quality-of-life comparisons in the area of antihypertensive therapy.
In one, a study conducted by Testa and researchers comparing quality of life in 379 patients being treated with either captopril or enalapril, no differences were found between the two agents in either efficacy or adverse effects.
However, a significant distinction was noted in Physical Symptom Distress Index scores (a measure of the distress caused by drug-related adverse effects) in favor of verapamil (P = 0.002), which corresponded to a difference between the two groups in quality-of-life scores. The variations in symptom distress scores tended to predict adherence; there were more discontinuations in the nifedipine group than in the verapamil group. The investigators concluded that measurement of symptom distress is a sensitive technique for evaluating the effect of antihypertensive therapy on quality of life.
Typically, adverse events are captured by recording symptoms spontaneously reported by patients; this is an insensitive method compared with prospectively capturing relevant side effects and their magnitude.
Symptom distress checklists as a component of quality of life measurement comparing prompted reports by patient and physician with concurrent adverse event reports via the physician.
A similar relationship between improved adverse effects and quality of life was reported in a randomized crossover trial in which transdermal fentanyl was compared with sustained-relief morphine in patients with chronic noncancer-related pain.
Allan L, Milligan K. Randomized, crossover and open-label trials demonstrate the efficacy of transdermal fentanyl (Duragesic®) for the treatment of chronic non-cancer pain. European League Against Rheumatism; Prague, Czech Republic; June 13–16, 2001. Abstract SAT0127.
In addition to more effective pain relief, fentanyl-treated patients reported significantly less trouble with side effects than those receiving morphine (P < 0.001). They also had significantly higher SF-36 scores in bodily pain, vitality, social functioning, and mental health (P < 0.005). These results suggest that tolerability may be a critical marker for quality of life.
Because NSAIDs, including cyclooxygenase-2 inhibitors (coxibs), provide analgesia by nonopioid mechanisms, they may have an opioid-sparing effect in patients treated with both agents. Opioid sparing via use of coxibs can be expected to decrease common quality-of-life-impairing adverse effects associated with opioids, including drowsiness, dizziness, constipation, nausea, and tolerance.29 These studies support the notion that drug therapies for pain can potentially be differentiated in terms of overall impact on quality of life, and that the most relevant driver of quality of life in this setting may be symptom distress due to medicinal side effects.
Future Directions in Quality-of-Life Research on Analgesics: Beyond Efficacy
The pain-relief efficacy of the coxibs is approximately equivalent to that of the nonselective nonsteroidal anti-inflammatory agents (NSAIDs). However, the lower risk of gastrointestinal (GI) adverse effects associated with the coxibs compared with traditional NSAIDs is an important quality-of-life consideration. Both rofecoxib and celecoxib have been shown, in very large randomized clinical trials (n = 8076 and 8059, respectively) to result in a significantly lower rate of GI ulcers, blood loss, intolerability, and other GI events relative to conventional NSAIDs.
Gastrointestinal toxicity with celecoxib vs nonsteroidal anti-inflammatory drugs for osteoarthritis and rheumatoid arthritis—the CLASS study A randomized controlled trial.
During nine months of follow-up, rofecoxib was found to be associated with 2.1 confirmed GI events per 100 patient-years compared with 4.5 events per 100 patient-years with naproxen (P < 0.001).
Celecoxib was associated with an annualized incidence rate of upper GI ulcer complications of 0.76% compared with a rate of 1.45% for ibuprofen or diclofenac (P = 0.09).
Gastrointestinal toxicity with celecoxib vs nonsteroidal anti-inflammatory drugs for osteoarthritis and rheumatoid arthritis—the CLASS study A randomized controlled trial.
Rather than depend on surrogate markers, however, future research should compare coxibs and nonselective NSAIDs with regard to effect on quality of life, focusing on symptom distress measurements. It is critical to examine whether overall quality of life is improved with coxibs compared with nonselective NSAIDs, based on improved tolerability. Similar comparisons of various opioids or modes of opioid administration should focus on quality of life.
Conclusion
Uncontrolled pain has a universal and profoundly negative effect on quality of life; no age group is spared, and no type of pain is excepted. There is ample evidence, however, that effective analgesia improves quality of life—a finding that makes inadequate efforts at pain control unacceptable. Opioid analgesics have been shown to improve quality of life for patients with chronic pain, as have nonnarcotic agents, including nonselective NSAIDs and coxibs. In addition to providing a realistic indicator of how a given treatment will affect patients' lives, quality-of-life indicators can also be used to differentiate two agents of the same pharmacologic class. Future research in the area of analgesic pharmacotherapy should include quality of life as a key variable. Analgesic agents should be compared both within and between classes, incorporating the use of symptom distress scales, which may be the most sensitive way of discriminating among analgesics in effects on quality of life. The meaningfulness of these differences can be addressed directly by methods that calibrate symptom distress to stressful real-life events or by using utility-based methods.
MayoClinic.com. Managing pain: attitude, medication and therapy are keys to control. Mayo Clinic Web Site. June 21, 2001. Available at: http://www. mayoclinic.com/invoke.cfm?id=HQ01055. Accessed September 19, 2001.
Joint Commission on Accreditation of Healthcare Organizations
Assessment of persons with pain. Pain Assessment and Management An Organizational Approach. Joint Commission on Accreditation of Healthcare Organizations;,
Oakbrook Terrace, IL2000: 13-25
Katz N, Davis MW, Dworkin R. Topical lidocaine patch produces a significant improvement in mean pain scores in treated PHN patients: results of a multicenter open-label trial. In: Posters of the 20th Annual Scientific Meeting of the American Pain Society; Phoenix, AZ; April 19–22, 2001; Poster 741.
Allan L, Milligan K. Randomized, crossover and open-label trials demonstrate the efficacy of transdermal fentanyl (Duragesic®) for the treatment of chronic non-cancer pain. European League Against Rheumatism; Prague, Czech Republic; June 13–16, 2001. Abstract SAT0127.
00411-6&id=gr1.gif){kind=link}
00411-6&id=gr2.gif){kind=link}
00411-6&id=gr3.jpg){kind=link}
00411-6&id=gr4.gif){kind=link}