Introduction

Chronic pain is a major cause of suffering, disability, lost productivity, and diminished quality of life across the entire life course. Cross-sectional studies have revealed that upward of 55% of adults experience chronic pain. Likewise, up to 45% of children experience at least one episode of chronic pain, with an attendant similar adverse effect on their daily activities and quality of life. Many pediatric patients with chronic pain eventually experience similar recurrent pain as adults.

In its 2011 report Relieving Pain in America: A Blueprint for Transforming Prevention, Care, Education, and Research , the Institute of Medicine (IOM) estimated that more than 116 million Americans struggle with chronic pain—greater than the combined prevalence of heart disease, cancer, and diabetes—which results in associated medical cost and lost productivity of US $635 billion annually. Even in a country such as Canada, with its more constrained, universal health insurance, the recently estimated (and escalating) yearly expenditure of Can $3500 per chronic pain sufferer translates into annual direct system costs of greater than Can $400 million. Acute pain also has major adverse effects on individual health and well-being, as well as a major impact on the health care delivery system. Furthermore, inadequate treatment of acute postoperative and traumatic pain in adults and children can lead to particularly severe and unremitting chronic pain.

Based on focus groups of key stakeholders, six major themes have been identified by the Pain Action Initiative: A National Strategy (PAINS) regarding chronic pain, all of which speak to its interconnected ethical, economic, and health care policy elements ( Box 5.1 ). Pain management thus has a myriad of implications on major health care policy, several of which are discussed here. Health care policy per se is a very broad and continually evolving topic for which more comprehensive resources are available.

The Role of Economic Evaluation in Formulating Chronic Pain Management Policy

The individual and societal costs of pain are multifaceted and extensive, and it is essential that informed policy makers and practitioners be fully aware of them ( Box 5.2 ). Of note, the acute and chronic pain-related cost borne by the individual, such as uninsured treatments, informal care, and intangibles related to loss of quality of life, is unquestionably substantial but difficult to estimate, and consequently it is often underappreciated.

As discussed in the current accompanying chapter on clinical trial design ( Chapter 80 ), appraisal of a new or existing treatment involves three aspects: efficacy , effectiveness , and efficiency . Even though randomized controlled trials can rigorously assess the efficacy of a pain treatment, their findings often lack external validity (generalizability to other settings). This weakness underscores the need for more naturalistic observational studies of treatment effectiveness in real-world practice (e.g., as part of multidrug, multimodal pain therapy, in more demographically and clinically diverse patients, and for much longer periods).

There are simply not enough financial resources in the health care systems around the world—even in the most developed countries—to fund all technically feasible and potentially beneficial health care interventions. Given such inevitably constrained health care resources, difficult choices have to be made, and a formal economic evaluation offers a systematic and transparent process for informing such choices. Specifically, the comparative efficiency (incremental cost per clinical outcome) of a pain intervention can be determined. However, there is a great need for more robust, longitudinal cost-effectiveness studies on assessment and treatment of chronic pain.

Health care economic evaluation methods have matured considerably in the last 25 years, with a plethora of published resources. Nonetheless, despite widespread promotion to this audience, many physicians, health services researchers, and policy makers remain reluctant to apply economic evaluation methods in their clinical decision making and clinical trials. Much of this gap has been attributed to physicians and their inherent tendency to think more in terms of clinical effectiveness and advocacy at the individual patient level rather than about cost-effectiveness (efficiency) at the population or health policy level. This resistance to collecting, analyzing, and incorporating health economic data in the presently well-established era of both evidence-based medicine and demand for value in health care is particularly notable.

The Role of Economic Evaluation in Formulating Chronic Pain Management Policy

The individual and societal costs of pain are multifaceted and extensive, and it is essential that informed policy makers and practitioners be fully aware of them ( Box 5.2 ). Of note, the acute and chronic pain-related cost borne by the individual, such as uninsured treatments, informal care, and intangibles related to loss of quality of life, is unquestionably substantial but difficult to estimate, and consequently it is often underappreciated.

As discussed in the current accompanying chapter on clinical trial design ( Chapter 80 ), appraisal of a new or existing treatment involves three aspects: efficacy , effectiveness , and efficiency . Even though randomized controlled trials can rigorously assess the efficacy of a pain treatment, their findings often lack external validity (generalizability to other settings). This weakness underscores the need for more naturalistic observational studies of treatment effectiveness in real-world practice (e.g., as part of multidrug, multimodal pain therapy, in more demographically and clinically diverse patients, and for much longer periods).

There are simply not enough financial resources in the health care systems around the world—even in the most developed countries—to fund all technically feasible and potentially beneficial health care interventions. Given such inevitably constrained health care resources, difficult choices have to be made, and a formal economic evaluation offers a systematic and transparent process for informing such choices. Specifically, the comparative efficiency (incremental cost per clinical outcome) of a pain intervention can be determined. However, there is a great need for more robust, longitudinal cost-effectiveness studies on assessment and treatment of chronic pain.

Health care economic evaluation methods have matured considerably in the last 25 years, with a plethora of published resources. Nonetheless, despite widespread promotion to this audience, many physicians, health services researchers, and policy makers remain reluctant to apply economic evaluation methods in their clinical decision making and clinical trials. Much of this gap has been attributed to physicians and their inherent tendency to think more in terms of clinical effectiveness and advocacy at the individual patient level rather than about cost-effectiveness (efficiency) at the population or health policy level. This resistance to collecting, analyzing, and incorporating health economic data in the presently well-established era of both evidence-based medicine and demand for value in health care is particularly notable.

The Equity of Chronic Pain: How Can Science Guide Health Policy?

In addition to assessing the efficacy, effectiveness, and efficiency of a new or existing pain assessment or treatment modality, a fourth key health policy element is equity of patient access to comparable health care—including pain management. Pioneered by John Bonica and Wilbert Fordyce more than 50 years ago, a multidisciplinary pain treatment program has been advocated as the optimal way to manage chronic pain. This long-standing recognition of the merit of multidisciplinary pain treatment clinics, combined with an increasing prevalence of chronic pain, has led to a growth in demand, clinic waiting list size and time, and international concerns over limited pain treatment resources—all prompting the question of how can science guide health policy regarding chronic pain.

Given its national health insurance program (“universal coverage” framed by the Canada Health Act of 1984), Canada presents a unique opportunity to examine the health policy and economics of pain management in a developed country. An initial survey of Canadian multidisciplinary pain treatment facilities (MPTFs) conducted by the STOP-PAIN Research Group found the median wait time for a first appointment in public MPTFs to be 6 months, approximately 12 times longer than the wait time for nonpublic MPTFs. The existing capacity of MPTFs in all of Canada could meet only 20% of the demand. The authors and others concluded that current Canadian MPTFs are unable to meet the clinical needs of adult patients with chronic pain in terms of both regional accessibility and reasonable wait time for patients’ first appointment. The STOP-PAIN Research Group reported similarly inadequate access, with variable and prolonged wait times for pediatric patients suffering from chronic pain.

Two subsequent STOP-PAIN studies focused on the biopsychosocial and economic burden of adult patients on Canadian MPTF wait lists. In STOP-PAIN-1, patients on MPTF wait lists experienced severe pain (61%), marked limitations in activity (66%), significant depression (50%), and frequent suicide ideation (35%). These biopsychosocial findings from STOP-PAIN-1 are similar to those from large concurrent samples of pain treatment clinic patients in Australia and Germany. In STOP-PAIN-2, the median monthly cost was Can $1462 per study participant on an MPTF wait list, 95% of which was due to lost productivity (wages) and personal out-of-pocket expenses.

An extensive systematic review of the literature and a survey of International Association for the Study of Pain (IASP) chapter presidents and other key stakeholders identified no established benchmarks or guidelines for acceptable wait times for the treatment of chronic pain. However, another systematic literature review indicated that patients with chronic pain experience a significant deterioration in health-related quality of life and psychological well-being from the time of referral to treatment. This consistent pattern of evidence underscores the need to improve access to appropriate care for patients with chronic pain—an escalating public health problem with major human and economic cost.

Pain Management as a Global Public Health Priority and Human Right

The World Health Organization (WHO) has estimated that more than 80% of the world’s population is inadequately treated for moderate to severe pain and that 5 billion people live in countries with minimal to no appropriate access to controlled analgesics. Given this enormous worldwide burden, pain should ostensibly represent a major global public health concern. Yet pain management has been relatively neglected by national governmental agencies and international nongovernmental organizations. Acute, chronic, and cancer pain collectively represents the often unreported and hence silent dimension of many of the worldwide causes of both adult and pediatric morbidity and mortality. Although acute pain may reasonably be considered a symptom of disease, illness, or injury, chronic and recurrent pain is a specific health care problem—a disease in its own right. It has been persuasively posited that this pervasive view of chronic pain as a symptom of disease rather than a disease state in itself has contributed to the paucity of public health and health policy attention (and funding) that chronic pain has received.

Consequently, the WHO, IASP, and European Federation of the IASP chapters jointly declared in 2004 that such widespread, inadequately treated chronic pain must not be tolerated and, furthermore, that relief of pain should be a universal human right. In 2010 the IASP issued the Declaration of Montreal: Declaration That Access to Pain Management Is a Fundamental Human Right ( Box 5.3 ), which, in addition to emphasizing that chronic pain is a disease entity, reaffirmed the basic human right to access effective pain management and the obligation of governments and health care institutions to establish laws, policies, and systems that help promote—not inhibit—access to pain management.

The two ultimate aims of this ongoing global pain initiative are to inform policy makers about the personal burden and economic cost of chronic pain and to educate physicians and allied health care professionals about assessment and management of pain to promote higher standards of care worldwide. Similar attention has focused on effective palliative care being a universal, international human right. Finally, denial of adequate pain treatment, when used as a form of punishment or torture, is a grossly egregious human rights violation.

Increasing Worldwide Access to Analgesics

Even though simple, cost-effective treatments exist, a major gap exists between our increasingly sophisticated understanding of the pathophysiology of pain and its continued widespread inadequate management. Despite international human rights laws, calls for the reform of laws and policies inhibiting access to pain treatment worldwide, and the attendant obligation of sovereign states to provide their citizens access to pain relief medicine, obstacles still commonly exist in providing pain treatment and palliative care ( Box 5.4 ). Of the 42 million grams of morphine consumed legally worldwide in 2010, 78% went to six countries—Australia, Canada, France, Germany, the United Kingdom, and the United States ( Fig. 5.1 A ). As a result, access to even basic treatment, such as oral analgesics, including opioids (e.g., morphine), for cancer pain and antiepileptic and antidepressant drugs for neuropathic pain, is widely variable and commonly deficient ( Fig. 5.1 A and B ).

A, Global per capita consumption of morphine. B, Maldistribution of regional legal opioid consumption versus population and morphine distribution of consumption, 2010. Note : Percentages in parentheses refer to share of the world population (i.e., total population of all reporting countries).

(From International Narcotics Control Board. Available at http://www.incb.org/ .)

Pain is a universal, multicultural experience that affects all people regardless of demographics or geography; however, inadequate treatment and the adverse effects of pain are not equally distributed worldwide. This gap is most apparent and problematic in the poorest and most socially dysfunctional developing nations in Africa and Asia, which are contending with widespread poverty, oppression and violence, and sometimes war and its aftermath ( Fig. 5.2 ). However, a similar disparity in pain treatment exists in Europe between the European Union member countries and the former Iron Curtain Eastern European and Balkan countries. Many cancer patients in Eastern Europe do not receive adequate relief of pain because of excessive regulatory restrictions on the availability and accessibility of opioids. According to a Human Rights Watch report, the Ukraine is one of several Eastern European and Central Asian countries that consume only enough opioids in total to treat less than 30% of their citizens with terminal cancer and human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS). Pain medicine and palliative care practitioners thus need to advocate for reform of governmental policy to overcome impediments to patient access to opioids. For example, a 4-year project in which health care professionals collaborated with governmental officials culminated in the Romanian Parliament passing new, more progressive legislation on the medical use of opioids and psychotropic substances, with an ensuing nationwide practitioner educational program.

Regional access to pain treatment.

(From Human Rights Watch. Global State of Pain Treatment . New York: Human Rights Watch; 2011:1-23. Reprinted with permission.)

The Need for a More Comprehensive and Organized Approach to Prescribing Opioids Chronically

Although many in the world suffer needlessly, prescribing of opioids for chronic non–cancer-related pain has paradoxically escalated in the United States recently; yet such use has outpaced the growth of scientific evidence on the benefits and harm of these medications. Critical research gaps exist on use of opioids for chronic non–cancer-related pain, and the need for a stronger evidence base is hence urgent. Nevertheless, a recent multidisciplinary expert panel commissioned by the American Pain Society and the American Academy of Pain Medicine concluded that based on a systematic review of the available, albeit limited evidence, chronic opioid therapy can be an effective treatment in carefully selected and monitored patients with chronic non–cancer-related pain.

Even in countries such as the United States with its ample, if not perhaps overabundant supply of opioids, there are inconsistent prescribing patterns and thus frequently unequal and inadequate access to opioids. As with many other elements of the U.S. health care system, there are racial, socioeconomic, and age disparities in pain assessment and opioid prescribing patterns, with minorities, the poor, and the elderly less likely to have access to needed controlled substances. In many large U.S. medical centers, such marginalized patients with a legitimate need for opioids are customarily passed around from clinic to clinic. These patients thus out of necessity frequently visit emergency departments, where assessment and treatment of pain are widely variable and inadequate and where racial disparities in opioid prescribing also exist. An innovative pharmacy- and primary care–based chronic opioid management program (an “Opioid Renewal Clinic”) for such high-risk patients has been implemented successfully at the Philadelphia Veterans Affairs Medical Center. To be more widely applied, this comprehensive practice model requires close collaboration between primary care physicians and pain medicine specialists. However, there appears to be little support for such a labor-intensive, comparatively low-margin program among nongovernmental health care administrators and interventional pain practitioners.

Addressing Pain in the Especially Vulnerable Pediatric and Geriatric Populations

Given their respective potential and historically major societal contributions, it can be cogently argued that equitable and compassionate health care of children and the elderly is a hallmark of a just, higher-order society. It is thus quite problematic that the especially vulnerable pediatric and geriatric populations remain quite prone to inadequate pain management—even in developed countries.

There is abundant published guidance on the assessment and treatment of pediatric pain, as well as robust data on its widespread prevalence and adverse effects. Thus, inadequate pediatric management can no longer be attributed to a lack of evidence-based medicine but rather to an inability to apply what is known in everyday practices. Clinicians, educators, administrators, and policy makers have an individual and collective responsibility to decrease pain and suffering in children and adolescents by narrowing the gap between current clinical practice and the existing research evidence and ethics supporting optimal patient care. In developed countries, including the United States, Canada, and the United Kingdom, there is a need for increased training, resources, and reimbursement for primary care physicians and pain clinicians who seek to manage pediatric chronic pain via an often indicated biopsychosocial approach. This need is especially great in smaller communities and rural settings, which are typically quite distant from formal pediatric pain medicine programs. However, the situation is even more dire throughout the developing world (in low- and middle-income countries), where access to even basic pain treatment services is largely unavailable to the vast majority of children and adolescents who suffer pain from diseases (e.g., HIV/AIDS, cancer, sickle cell disease) and trauma (e.g., injury, burns, war, terrorism, land mines). The scope of this collective pediatric suffering and a global plan of action have been detailed by the WHO and a group of invested clinicians.

At the other end of the age spectrum, assessment and treatment of geriatric pain have also been well described. Nevertheless, chronic pain affects an estimated 25% to 50% of elderly people living in the community. Geriatric chronic pain management remains similarly suboptimal, with improvement needed in screening, clinical evaluation, follow-up, and attention to potential toxicities of therapy. In 2009 the American Geriatric Society recommend low-dose, low-potency opioids (e.g., hydrocodone) over a nonsteroidal anti-inflammatory drug (NSAID; [e.g., ibuprofen]) as the first-line drug of choice for all elderly patients with moderate to severe pain, pain-related functional impairment, or diminished quality of life because of pain. Two subsequently published, large-scale, retrospective analyses of Medicare claims data have questioned these recommendations. In a cohort of arthritis patients (mean age of 80 years, 85% female), the use of opioids was associated with a greater risk for cardiovascular events, safety events requiring hospitalization, and all-cause mortality than was the use of NSAIDs. In the same database of patients, the risk for fractures of the hip, pelvis, wrist, or humerus was lower with propoxyphene and tramadol than with codeine, hydrocodone, and oxycodone. Despite the use of propensity score matching to balance the potentially confounding covariates identified, these authors did not consider the potential dose-response gradient or account for key confounders, such as over-the-counter analgesic use and gastrointestinal bleeding, functional status and falls, and tobacco exposure and cardiovascular events. The National Institutes of Health Pain Consortium recently sponsored an “Expert Panel Discussion on the Pharmacological Management of Chronic Pain in Older Adults” to identify research gaps and strategies to address them. This 2010 panel focused specifically on the use of opioids and NSAIDs because of these continued uncertainties regarding their risks versus benefits.

Nursing home residents are a particularly vulnerable group of elders. The Centers for Disease Control and Prevention estimated that there are currently 1.5 million nursing home residents in the United States and that 43% of Americans older than 65 years will enter a nursing home at some point in their lives, with an average 835-day length of time since initial admission. Pain is a common symptom in older residents of nursing homes and can lead to adverse effects such as a decrease in activities of daily living and quality of life. Over the last 20 years the reported multinational prevalence of pain in nursing home residents has varied from 3.7% to 79.5%. Moreover, a very large-scale U.S. cross-sectional study of nursing home residents 65 years and older revealed 17% to have substantial daily pain, but this prevalence of daily pain ranged from 0% to 54.7% by individual facility. Thus not surprisingly, regulatory agencies, health care policy makers and administrators, health services researchers, and clinicians have identified improving pain assessment and treatment in nursing homes as a high priority. However, there has been little consensus about the best strategies to optimize pain management in nursing homes. Given the unique population and care environment, clinical leadership in nursing homes needs not only proficient pain assessment and treatment skills but also working knowledge of organizational change, including quality improvement, team building, collaborative decision making, and system-level problem solving. Of note, failure to provide adequate pain control in the nursing home setting has been legally interpreted as elder abuse.

The Regulatory Process for Drugs and Medical Devices

It is worthwhile to compare, contrast, and critique the regulatory processes by which new drugs and medical devices are reviewed and approved for marketing and clinical use. In the United States, the Center for Drug Evaluation and Research (CDER) of the Food and Drug Administration (FDA) is primarily responsible for assessing the safety and efficacy of a new drug. As a new drug makes its way through this federal regulatory and approval process, a series of four phases are defined by the FDA CDER ( Table 5.1 ). Medical devices are regulated in the United States by the FDA Center for Devices and Radiological Health (CDRH). The FDA CDRH classifies a new medical device according to its perceived risk by using a three-tiered system (class I, II, or III), with escalating supporting evidence required for efficacy and safety and for postmarket surveillance ( Table 5.2 ).

In a similar manner, the Australian Drug Evaluation Committee makes recommendations to the national Therapeutic Goods Administration. As in the United States, after a drug is initially approved, marketed, and distributed in Australia, it is considered eligible for phase IV trials in which new or expanded uses or populations (or both) can be approved and long-term risk versus benefits explored. In the European Union, either a state (i.e., country) level or a more centralized process is followed for drug approval. In the more centralized process, the Committee for Human Medicinal Products evaluates and makes recommendations to the European Medicines Agency (EMA), which grants community marketing authorization. In the United Kingdom, after a drug is approved and licensed by the EMA, it undergoes further review for clinical indications and cost-effectiveness by the National Institute for Health and Clinical Excellence (NICE) in England and Wales or the Scottish Medicines Consortium in Scotland, which must approve its use by the respective branch of the National Health Service.

In China, under the auspices of the State Food and Drug Administration, the Center for Drug Evaluation oversees approval of new drugs for marketing, with the new drug approval and registration process predicated on suitable clinical study data. In India, the Central Drugs Standard Control Organization undertakes the data review process and makes recommendations to the Drugs Controller General. Drugs previously approved in the United States, Great Britain, Switzerland, Australia, Canada, Germany, South Africa, Japan, or the European Union (category A) are eligible for fast tracking in India, whereas in the absence of such a previous national approval, a similar multiphase process (category B) is followed.

Given this very similar drug regulatory structure and process, one might expect a similar level of evidence required (i.e., threshold) and time line for approval; however, such is not the case. In the United States the threshold for regulatory approval of a pharmaceutical is much lower than in Canada, the United Kingdom, and the European Union. Under the current Code of Federal Regulations, new drug approval by the U.S. FDA is typically based on demonstration of efficacy in only two or more randomized clinical trials, often in comparison to placebo—not the currently approved competing generic drug. Given the perceived continued progress of medical science, governmental marketing approval of a new drug implies to clinicians and the general public that the new product represents an advance over older treatments. However, these current FDA standards for approval fail to assess whether newly approved drugs are less efficacious or less well tolerated than existing, often lower-cost alternatives. This raises the possibility that patients may be harmed by receiving a newly approved, typically more expensive, yet less efficacious treatment instead of a less costly alternative with well-established effectiveness and safety. Aggressive pharmaceutical industry marketing to clinicians, as well as directly to consumers in the United States, increases the likelihood of this scenario.

In contrast, health care systems in several developed countries (e.g., Australia, Canada, and Britain) are applying comparative effectiveness research methods to allow decision makers (patients, clinicians, purchasers, politicians, and policy makers) to make informed decisions on specific health practices. Such countries are now specifically using cost-effectiveness analysis—a form of comparative effectiveness research—to make drug approval decisions and to determine what medications will be reimbursed from the finitely available collective funding. Such a cost-effectiveness analysis involves a head-to-head comparison of the cost and outcomes of the proposed proprietary drug versus an existing (if available, generic) drug. A similar approach is used for so-called “me too” drugs. NICE makes such decisions in the British National Health Service. The cost-effectiveness–based approval process used by NICE has not been without controversy—with some clinicians and patients deriding it as being tantamount to overt rationing of health care and restricting access to potentially vital therapies. Supporters of the NICE system argue that markedly higher patient co-payments for such drugs in the United States amount to barriers to access and covert rationing.

Some have contended that the introduction of a new medical device into clinical practice is typically and unnecessarily delayed between 1 and 3 years in the United States when compared with the European Union. This is especially so with class III high-risk devices, which to receive approval for marketing in the United States, the manufacturer must demonstrate the device to be reasonably safe and effective, typically with a prospective, randomized controlled clinical trial. To receive approval to market the same device in the European Union, the manufacturer must demonstrate only that it is safe and that it performs in a manner consistent with the manufacturer’s intended use. Nevertheless, in recent years, well-publicized device recalls and lawsuits in the United States have led to concern that the FDA does not require sufficiently well-designed and valid supporting studies and does not keep unsafe devices off the market. A recent study observed that of 78 class III (“high risk”) cardiovascular devices that were approved through the FDA full premarket approval (PMA) process between 2000 and 2007, only 27% of the devices had been subjected to a single randomized trial and only 5% had undergone two or more blinded randomized studies. The failure of certain medical devices such as implantable defibrillators—despite full PMA by the FDA—could pose deadly risks. Of the 113 medical devices recalled from 2005 through 2009 by the FDA for life-threatening or very serious hazards, 78% were originally approved for marketing under the less stringent Section 510(k) FDA process or were considered so low risk that they were exempt from review.