Shannon M. Smith

Are you happy for me? How sharing positive events with others provides personal and interpersonal benefits.

Sharing good news with others is one way that people can savor those experiences while building personal and interpersonal resources. Although prior research has established the benefits of this process, called capitalization, there has been little research and no experiments to examine the underlying mechanisms. In this article, we report results from 4 experiments and 1 daily diary study conducted to examine 2 mechanisms relevant to capitalization: that sharing good news with others increases the perceived value of those events, especially when others respond enthusiastically, and that enthusiastic responses to shared good news promote the development of trust and a prosocial orientation toward the other. These studies found consistent support for these effects across both interactions with strangers and in everyday close relationships.

Classification and definition of misuse, abuse, and related events in clinical trials: ACTTION systematic review and recommendations

Abstract Terminology related to prescription drug misuse and abuse is inconsistently defined. An expert panel developed consensus classifications and definitions for use in clinical trials. Abstract As the nontherapeutic use of prescription medications escalates, serious associated consequences have also increased. This makes it essential to estimate misuse, abuse, and related events (MAREs) in the development and postmarketing adverse event surveillance and monitoring of prescription drugs accurately. However, classifications and definitions to describe prescription drug MAREs differ depending on the purpose of the classification system, may apply to single events or ongoing patterns of inappropriate use, and are not standardized or systematically employed, thereby complicating the ability to assess MARE occurrence adequately. In a systematic review of existing prescription drug MARE terminology and definitions from consensus efforts, review articles, and major institutions and agencies, MARE terms were often defined inconsistently or idiosyncratically, or had definitions that overlapped with other MARE terms. The Analgesic, Anesthetic, and Addiction Clinical Trials, Translations, Innovations, Opportunities, and Networks (ACTTION) public–private partnership convened an expert panel to develop mutually exclusive and exhaustive consensus classifications and definitions of MAREs occurring in clinical trials of analgesic medications to increase accuracy and consistency in characterizing their occurrence and prevalence in clinical trials. The proposed ACTTION classifications and definitions are designed as a first step in a system to adjudicate MAREs that occur in analgesic clinical trials and postmarketing adverse event surveillance and monitoring, which can be used in conjunction with other methods of assessing a treatment’s abuse potential.

Patient phenotyping in clinical trials of chronic pain treatments: IMMPACT recommendations.

Abstract There is tremendous interpatient variability in the response to analgesic therapy (even for efficacious treatments), which can be the source of great frustration in clinical practice. This has led to calls for “precision medicine” or personalized pain therapeutics (ie, empirically based algorithms that determine the optimal treatments, or treatment combinations, for individual patients) that would presumably improve both the clinical care of patients with pain and the success rates for putative analgesic drugs in phase 2 and 3 clinical trials. However, before implementing this approach, the characteristics of individual patients or subgroups of patients that increase or decrease the response to a specific treatment need to be identified. The challenge is to identify the measurable phenotypic characteristics of patients that are most predictive of individual variation in analgesic treatment outcomes, and the measurement tools that are best suited to evaluate these characteristics. In this article, we present evidence on the most promising of these phenotypic characteristics for use in future research, including psychosocial factors, symptom characteristics, sleep patterns, responses to noxious stimulation, endogenous pain-modulatory processes, and response to pharmacologic challenge. We provide evidence-based recommendations for core phenotyping domains and recommend measures of each domain.

Abuse liability measures for use in analgesic clinical trials in patients with pain: IMMPACT recommendations

Summary Assessing and mitigating the abuse liability (AL) of analgesics is an urgent clinical and societal problem. Recommendations for improved assessment include: (1) performing trials that include individuals with diverse risks of abuse; (2) improving the assessment of AL in clinical trials (eg, training study personnel in the principles of abuse and addiction behaviors, designing the trial to assess AL outcomes as primary or secondary outcome measures depending on the trial objectives); (3) performing standardized assessment of outcomes, including targeted observations by study personnel and using structured adverse events query forms that ask all subjects specifically for certain symptoms (such as euphoria and craving); and (4) collecting detailed information about events of potential concern (eg, unexpected urine drug testing results, loss of study medication, and dropping out the trial). Abstract Assessing and mitigating the abuse liability (AL) of analgesics is an urgent clinical and societal problem. Analgesics have traditionally been assessed in randomized clinical trials (RCTs) designed to demonstrate analgesic efficacy relative to placebo or an active comparator. In these trials, rigorous, prospectively designed assessment for AL is generally not performed. The Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) convened a consensus meeting to review the available evidence and discuss methods for improving the assessment of the AL of analgesics in clinical trials in patients with pain. Recommendations for improved assessment include: (1) performing trials that include individuals with diverse risks of abuse; (2) improving the assessment of AL in clinical trials (eg, training study personnel in the principles of abuse and addiction behaviors, designing the trial to assess AL outcomes as primary or secondary outcome measures depending on the trial objectives); (3) performing standardized assessment of outcomes, including targeted observations by study personnel and using structured adverse events query forms that ask all subjects specifically for certain symptoms (such as euphoria and craving); and (4) collecting detailed information about events of potential concern (eg, unexpected urine drug testing results, loss of study medication, and dropping out of the trial). The authors also propose a research agenda for improving the assessment of AL in future trials.

Adherence to CONSORT harms-reporting recommendations in publications of recent analgesic clinical trials: an ACTTION systematic review.

Summary Harms reporting in analgesic trials of pharmacologic treatments has improved modestly since the 2004 CONSORT extension, although improvement may be related to other study factors. ABSTRACT Recommendations for harms (ie, adverse events) reporting in randomized clinical trial publications were presented in a 2004 extension of the Consolidated Standards of Reporting Trials (CONSORT) statement. Our objectives were to assess harms reporting in 3 major pain journals (European Journal of Pain, Journal of Pain, and PAIN®) to determine whether harms reporting improved following publication of the 2004 CONSORT recommendations, and to examine study factors associated with adequacy of harms reporting. A total of 101 randomized, double‐blind, noninvasive pharmacologic trials were identified in the 2000–2003 (epoch 1) and 2008–2011 (epoch 2) issues of these journals. Out of 10 reporting recommendations, the mean number fulfilled was 6.08 (SD 2.65). Although more harms recommendations were fulfilled in epoch 2 (m2 = 6.49, SD 2.66) than in epoch 1 (m1 = 5.39, SD 2.52; P = 0.04), only the recommendation to report harms per arm was satisfied by >90% of trials in epoch 2, whereas <60% reported withdrawals due to harms. Several trial characteristics (study design, participant type, pain type, frequency of treatment administration, treatment administration method, sponsor, and number of randomized participants) were significantly associated with harms reporting. However, when trial characteristics and epoch were entered into a multiple regression analysis, only trials studying pain patients, those using oral treatments, and industry‐sponsored trials were associated with better harms reporting. Despite some improvement in harms reporting, greater improvement is needed to provide informative, consistent reporting of adverse events and safety in analgesic clinical trials.

Adverse event assessment, analysis, and reporting in recent published analgesic clinical trials: ACTTION systematic review and recommendations

&NA; Adverse events in randomized controlled trials of noninvasive, pharmacologic analgesics are frequently incompletely or inconsistently reported. A comprehensive reporting checklist is proposed to improve disclosure of adverse effects. &NA; The development of valid and informative treatment risk–benefit profiles requires consistent and thorough information about adverse event (AE) assessment and participants’ AEs during randomized controlled trials (RCTs). Despite a 2004 extension of the Consolidated Standards of Reporting Trials (CONSORT) statement recommending the specific AE information that investigators should report, there is little evidence that analgesic RCTs adequately adhere to these recommendations. This systematic review builds on prior recommendations by describing a comprehensive checklist for AE reporting developed to capture clinically important AE information. Using this checklist, we coded AE assessment methods and reporting in all 80 double‐blind RCTs of noninvasive pharmacologic treatments published in the European Journal of Pain, Journal of Pain, and PAIN® from 2006 to 2011. Across all trials, reports of AEs were frequently incomplete, inconsistent across trials, and, in some cases, missing. For example, >40% of trials failed to report any information on serious adverse events. Trials of participants with acute or chronic pain conditions and industry‐sponsored trials typically provided more and better‐quality AE data than trials involving pain‐free volunteers or trials that were not industry sponsored. The results of this review suggest that improved AE reporting is needed in analgesic RCTs. We developed an ACTTION (Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks) AE reporting checklist that is intended to assist investigators in thoroughly and consistently capturing and reporting these critically important data in publications.

Reporting of missing data and methods used to accommodate them in recent analgesic clinical trials: ACTTION systematic review and recommendations

Summary This article reports deficiencies in reporting of missing data and methods to accommodate them, reviews methods to accommodate missing data that were recommended by statisticians and regulators, and provides recommendations for authors, reviewers, and editors pertaining to reporting of these important statistical details. ABSTRACT Missing data in clinical trials can bias estimates of treatment effects. Statisticians and government agencies recommend making every effort to minimize missing data. Although statistical methods are available to accommodate missing data, their validity depends on often untestable assumptions about why the data are missing. The objective of this study was to assess the frequency with which randomized clinical trials published in 3 major pain journals (ie, European Journal of Pain, Journal of Pain, and Pain) reported strategies to prevent missing data, the number of participants who completed the study (ie, completers), and statistical methods to accommodate missing data. A total of 161 randomized clinical trials investigating treatments for pain, published between 2006 and 2012, were included. Approximately two‐thirds of the trials reported at least 1 method that could potentially minimize missing data, the most common being allowance of concomitant medications. Only 61% of the articles explicitly reported the number of patients who were randomized and completed the trial. Although only 14 articles reported that all randomized participants completed the study, fewer than 50% of the articles reported a statistical method to accommodate missing data. Last observation carried forward imputation was used most commonly (42%). Thirteen articles reported more than 1 method to accommodate missing data; however, the majority of methods, including last observation carried forward, were not methods currently recommended by statisticians. Authors, reviewers, and editors should prioritize proper reporting of missing data and appropriate use of methods to accommodate them so as to improve the deficiencies identified in this systematic review.

Assessment of physical function and participation in chronic pain clinical trials: IMMPACT/OMERACT recommendations.

Abstract Although pain reduction is commonly the primary outcome in chronic pain clinical trials, physical functioning is also important. A challenge in designing chronic pain trials to determine efficacy and effectiveness of therapies is obtaining appropriate information about the impact of an intervention on physical function. The Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) and Outcome Measures in Rheumatology (OMERACT) convened a meeting to consider assessment of physical functioning and participation in research on chronic pain. The primary purpose of this article is to synthesize evidence on the scope of physical functioning to inform work on refining physical function outcome measurement. We address issues in assessing this broad construct and provide examples of frequently used measures of relevant concepts. Investigators can assess physical functioning using patient-reported outcome (PRO), performance-based, and objective measures of activity. This article aims to provide support for the use of these measures, covering broad aspects of functioning, including work participation, social participation, and caregiver burden, which researchers should consider when designing chronic pain clinical trials. Investigators should consider the inclusion of both PROs and performance-based measures as they provide different but also important complementary information. The development and use of reliable and valid PROs and performance-based measures of physical functioning may expedite development of treatments, and standardization of these measures has the potential to facilitate comparison across studies. We provide recommendations regarding important domains to stimulate research to develop tools that are more robust, address consistency and standardization, and engage patients early in tool development.

Discrepancies between registered and published primary outcome specifications in analgesic trials: ACTTION systematic review and recommendations.

Summary Widespread discrepancies between registered vs published primary outcomes raise questions about whether published primary outcomes are prespecified. Recommendations are proposed to ensure the veracity of published primary outcome specifications. Abstract The National Institutes of Health released the trial registry ClinicalTrials.gov in 2000 to increase public reporting and clinical trial transparency. This systematic review examined whether registered primary outcome specifications (POS; ie, definitions, timing, and analytic plans) in analgesic treatment trials correspond with published POS. Trials with accompanying publications (n = 87) were selected from the Repository of Registered Analgesic Clinical Trials (RReACT) database of all postherpetic neuralgia, diabetic peripheral neuropathy, and fibromyalgia clinical trials registered at ClinicalTrials.gov as of December 1, 2011. POS never matched precisely; discrepancies occurred in 79% of the registry–publication pairs (21% failed to register or publish primary outcomes [PO]). These percentages did not differ significantly between industry and non‐industry‐sponsored trials. Thirty percent of the trials contained unambiguous POS discrepancies (eg, omitting a registered PO from the publication, “demoting” a registered PO to a published secondary outcome), with a statistically significantly higher percentage of non‐industry‐sponsored than industry‐sponsored trials containing unambiguous POS discrepancies. POS discrepancies due to ambiguous reporting included vaguely worded PO registration; or failing to report the timing of PO assessment, statistical analysis used for the PO, or method to address missing PO data. At best, POS discrepancies may be attributable to insufficient registry requirements, carelessness (eg, failing to report PO assessment timing), or difficulty uploading registry information. At worst, discrepancies could indicate investigator impropriety (eg, registering imprecise PO [“pain”], then publishing whichever pain assessment produced statistically significant results). Improvements in PO registration, as well as journal policies requiring consistency between registered and published PO descriptions, are needed.

Reporting of primary analyses and multiplicity adjustment in recent analgesic clinical trials: ACTTION systematic review and recommendations

Summary Deficiencies in reporting of primary analyses and multiplicity adjustment methods are summarized, and recommendations are provided for authors, reviewers, and editors pertaining to reporting of these important statistical details. ABSTRACT Performing multiple analyses in clinical trials can inflate the probability of a type I error, or the chance of falsely concluding a significant effect of the treatment. Strategies to minimize type I error probability include prespecification of primary analyses and statistical adjustment for multiple comparisons, when applicable. The objective of this study was to assess the quality of primary analysis reporting and frequency of multiplicity adjustment in 3 major pain journals (ie, European Journal of Pain, Journal of Pain, and PAIN®). A total of 161 randomized controlled trials investigating noninvasive pharmacological treatments or interventional treatments for pain, published between 2006 and 2012, were included. Only 52% of trials identified a primary analysis, and only 10% of trials reported prespecification of that analysis. Among the 33 articles that identified a primary analysis with multiple testing, 15 (45%) adjusted for multiplicity; of those 15, only 2 (13%) reported prespecification of the adjustment methodology. Trials in clinical pain conditions and industry‐sponsored trials identified a primary analysis more often than trials in experimental pain models and non‐industry‐sponsored trials, respectively. The results of this systematic review demonstrate deficiencies in the reporting and possibly the execution of primary analyses in published analgesic trials. These deficiencies can be rectified by changes in, or better enforcement of, journal policies pertaining to requirements for the reporting of analyses of clinical trial data.