The number of Americans age 65 or older currently exceeds 40 million, or about 13% of the US population. Over the next 20 years, this number is expected to reach approximately 70 million, or 20% of the population. The oldest old, those individuals age 85 or older, are the fastest growing segment of the US population, and the proportion of these individuals is expected to more than triple by 2050.
As the age of the population increases, so too will the diseases and conditions that accompany advancing age. Chronic pain is highly prevalent among older adults. Primary causes of chronic pain in this population include musculoskeletal diseases (e.g., osteoarthritis and degenerative disk disease), cancer, and neuropathic conditions (e.g., diabetic neuropathy, post-herpetic neuralgia, and chemotherapy-induced neuralgia). Chronic pain is also associated with a variety of adverse health outcomes such as disability, cognitive deficits, mood disturbance, and impaired sleep.
Current management of chronic pain involves a stepwise approach that frequently includes non-steroidal anti-inflammatory drugs (NSAIDs) and/or opioids for moderate-to-severe pain. A variety of adjuvant drugs, devices, and non-pharmacologic therapies may also be used, often in combination with NSAIDs and/or opioids. Despite this panoply of therapeutic options, however, older adults continue to be undertreated disproportionately, due in large part to lack of evidence, under-recognition of pain, and safety concerns among prescribers, patients, and caregivers.
In 2009, an American Geriatrics Society (AGS) special panel published updated guidelines for pharmacologic management of chronic pain in older adults . Specifically, these guidelines recommended that "[n]onselective NSAIDs and COX-2 selective inhibitors may be considered rarely, and with extreme caution, in highly selected individuals." At the same time, the AGS guidelines also recommended that "[a]ll patients with moderate to severe pain, pain-related functional impairment, or diminished quality of life due to pain should be considered for opioid therapy." While there is a fair amount of evidence supporting contraindications to treatment, there is a much smaller evidentiary base to identify those older adults with chronic pain who may safely benefit from NSAIDs or opioids over months or years of treatment. The evidence base for other classes of drugs, such as adjuvant analgesics, also requires further development.
Consequently, there is a need to generate evidence guiding safe and effective treatment for chronic pain in older persons. In 2010, an "Expert Panel Discussion on Pharmacological Management of Chronic Pain in Older Adults" was convened under the aegis of the NIH Pain Consortium to identify research gaps and suggest approaches to address them. A summary of the research gaps and methods to address them are in press at Pain Medicine with publication expected in the September, 2011 issue. Among many recommendations, panelists noted that a variety of factors may influence the selection and outcomes of treatment, including patient-, medication-, provider-, and system-level factors. A cost-effective approach to investigating these myriad factors may be to examine available datasets or add new measures to existing studies to identify variables associated with successful or adverse outcomes of treatment.
The purpose of this FOA is to support small, self-contained research projects that aim to leverage existing data or longitudinal studies in order to evaluate the safety and/or effectiveness of pharmacological management for chronic pain in older adults. Applicants are invited to submit innovative proposals using administrative databases, health care records, clinical trial datasets, patient registries, cohort studies, or other resources to further our understanding of treatment outcomes from pharmacologic or combination pharmacologic/non-pharmacologic interventions, particularly involving NSAIDs or opioids, in older individuals with chronic pain. Proposed approaches may include, but are not limited to 1) secondary analyses of existing datasets; 2) adding new measures to existing observational or interventional studies; or 3) developing methodologies to facilitate the preceding two approaches.
Examples of aging-related studies that this FOA may support include, but are not restricted to:
- Identification of patient-level factors (e.g., cormorbidities, pharmacogenomic profiles, renal function, cognitive function, vulnerabilities), medication-level factors (e.g., initiating dose, titration method, specific pattern of analgesic use, mode of delivery, interactions with alcohol, benzodiazepines, anti-depressants, or other sedatives), provider-level factors (e.g., communication patterns with patients, attitudes and beliefs), and/or system-level factors (e.g., guideline recommendations, care models) associated with outcomes from specific treatment strategies (e.g., pharmacotherapy or combination pharmacotherapy/ non-pharmacologic therapy) in older adults with chronic pain.
- Comparative safety and/or effectiveness studies of different treatment approaches in older adults or in specific sub-populations (e.g., individuals with dementia), such as comparisons between primary treatments to reduce pain, co-administered treatments to reduce side effects, or additive treatments to enhance therapeutic effects.
- Development of a methodology to link datasets with complementary data elements in order to enable valid evaluations of pain treatment outcomes that would not be possible using datasets individually.
- Evaluation of the utility of pain-related measures or indices in guiding treatment initiation, titration, or discontinuation in specific older populations (e.g., individuals with dementia).
Investigators hypothesizing mediatory roles for specific characteristics on treatment outcomes are encouraged to provide an empirical or theoretical rationale for selecting such characteristics. In addition, investigators are encouraged to provide adequate analytic plans to address potential methodological pitfalls of analyzing observational data, especially those collected in non-randomized studies or during clinical care.
Applicants are encouraged to study older subjects with a range of ages. Studies in older subjects with multiple morbidities, vulnerabilities, and those from ethnically diverse backgrounds are particularly encouraged, as these populations are among the most commonly undertreated and understudied patients with chronic pain.
The NIA Database of Longitudinal Studies contains an extensive listing of NIH-supported cohort studies involving older subjects and/or aging research questions. The database can be found at http://nihlibrary.ors.nih.gov/niapopdb/.
The National Institute on Drug Abuse (NIDA) is also interested in applications responsive to this FOA that fall within its scientific mission. NIDA may support such meritorious applications contingent on availability of funds.
1. American Geriatrics Society Panel on the Pharmacological Management of Persistent Pain in Older Persons. Pharmacological management of persistent pain in older persons: American Geriatrics Society. Journal of the American Geriatrics Society. 2009; 57:1331-1346.