The importance of patient-reported outcomes: a call for their comprehensive integration in cardiovascular clinical trials.

Patient-reported outcomes (PROs), such as symptoms, health-related quality of life (HRQOL), or patient perceived health status, are reported directly by the patient and are powerful tools to inform patients, clinicians, and policy-makers about morbidity and 'patient suffering', especially in chronic diseases. Patient-reported outcomes provide information on the patient experience and can be the target of therapeutic intervention. Patient-reported outcomes can improve the quality of patient care by creating a holistic approach to clinical decision-making; however, PROs are not routinely used as key outcome measures in major cardiovascular clinical trials. Thus, limited information is available on the impact of cardiovascular therapeutics on PROs to guide patient-level clinical decision-making or policy-level decision-making. Cardiovascular clinical research should shift its focus to include PROs when evaluating the efficacy of therapeutic interventions, and PRO assessments should be scientifically rigorous. The European Society of Cardiology and other professional societies can take action to influence the uptake of PRO data in the research and clinical communities. This process of integrating PRO data into comprehensive efficacy evaluations will ultimately improve the quality of care for patients across the spectrum of cardiovascular disease.

Development and validation of a new clinically-meaningful rating scale for measuring lateral canthal line severity.

BACKGROUND: Several scales have been employed for evaluating the effects of cosmetic treatments in the periorbital area. The Food and Drug Administration (FDA) has recently issued new recommendations specifying a rigorous process to validate new aesthetic scales. OBJECTIVES: The authors describe and validate a new clinical rating scale: the Investigator's Global Assessment of Lateral Canthal Line (IGA-LCL) severity scale. METHODS: The new FDA recommendations were utilized to validate the new scale. The first step was concept elicitation (based on direct input from clinicians, patients, and literature) and evaluation of content validity (appropriateness of concepts). The resulting five-point scale provided detailed descriptions of the lateral canthal lines (LCL), including quantitative assessment of LCL length and depth. Performance parameters, including intra- and interrater reproducibility and construct validity, were then evaluated in clinical studies. Finally, the scale's threshold for clinically-meaningful benefit and the ability of the scale to detect change were confirmed in two Phase 2b clinical studies involving a total of 270 subjects. RESULTS: Content validity was established and the IGA-LCL scale showed excellent interrater reliability (weighted Kappa = 0.89) and interrater reliability (weighted Kappa = 0.77; Kendall's coefficient of concordance = 0.89). In clinical trials, the scale was sensitive enough to detect clinically-meaningful one- and two-point changes in LCL severity following treatment with topical botulinum toxin type A (BoNT-A). The authors observed statistically-significant correlations between the physician-rated IGA-LCL results and patient-reported outcomes. CONCLUSIONS: The IGA-LCL scale was shown to be reliable, appropriate, and clinically meaningful for measuring LCL severity.

Moderators of naltrexone's effects on drinking, urge, and alcohol effects in non-treatment-seeking heavy drinkers in the natural environment.

BACKGROUND: Naltrexone (NTX) has proven to be effective with alcoholics in treatment, with most controlled clinical trials showing beneficial effects on heavy drinking rates. However, little is known about the behavioral mechanisms underlying the effects of NTX on drinking, or about patient characteristics that may moderate NTX's effects on drinking. In this study, ecological momentary assessment (EMA) techniques were used to investigate some of the putative mechanisms of naltrexone's effects on drinking in heavy drinkers who were not seeking treatment for alcohol problems. Polymorphisms in the D4 dopamine receptor (DRD4) gene and the mu-opiate receptor (OPRM1) gene, family history of alcohol problems, age of onset of alcoholism and gender were explored as potential moderators of NTX's effects. METHODS: After a 1-week placebo lead-in period, heavy drinkers (n = 180), 63% of whom were alcohol-dependent, were randomized to 3 weeks of daily naltrexone (50 mg) or placebo. Throughout the study, participants used EMA on palm-pilot computers to enter, in real time, drink data, urge levels, and subjective effects of alcohol consumption. RESULTS: Naltrexone reduced percentage drinking days in all participants and reduced percent heavy drinking days in DRD4-L individuals; NTX decreased urge levels in participants with younger age of alcoholism onset; NTX increased time between drinks in participants who had more relatives with alcohol problems; and NTX reduced the stimulating effects of alcohol in women. OPRM1 status did not moderate any of NTX's effects. CONCLUSIONS: These results confirm earlier findings of NTX's effects on drinking and related subjective effects, and extend them by describing individual difference variables that moderate these effects in the natural environment, using data collected in real time.

Prediction of lapse from associations between smoking and situational antecedents assessed by ecological momentary assessment.

Smoking is associated with particular moods and activities, but it is not known whether there are individual differences in these associations and whether these differences are associated with success in smoking cessation. We assessed such associations using ecological momentary assessment: real-world, real-time data, collected by palm-top computer. Two hundred and fourteen smokers participating in a smoking cessation study provided data during ad lib smoking at baseline. Participants recorded moods and activities each time they smoked and, for comparison, at randomly selected non-smoking occasions. Situational associations with smoking were captured by examining the associations between smoking and antecedents considered relevant to lapse risk: negative affect (NA), arousal, socializing with others, the presence of others smoking, and consumption of coffee and alcohol. The associations varied across participants, confirming individual differences in situational smoking associations. Survival analyses revealed that only the NA pattern predicted first lapse. The effect was only seen in EMA assessments of NA smoking, and was not captured by questionnaire measures of negative affect smoking, which did not predict lapse risk. Moreover, the effect was not mediated by nicotine dependence.

Dynamic self-efficacy and outcome expectancies: prediction of smoking lapse and relapse.

According to social learning models of drug relapse, decreases in abstinence self-efficacy (ASE) and increases in positive smoking outcome expectancies (POEs) should foreshadow lapses and relapse. In this study, the authors examined this hypothesis by using ecological momentary assessment data from 305 smokers who achieved initial abstinence from smoking and monitored their smoking and their ASE and POEs by using palmtop computers. Daily ASE and POEs predicted the occurrence of a 1st lapse on the following day. Following a lapse, variations in daily ASE predicted the onset of relapse, even after controlling for concurrent smoking. ASE and POEs generally neither mediated nor moderated each other's effects. These data emphasize the role of dynamic factors in the relapse process.

The morning after: limit violations and the self-regulation of alcohol consumption.

The authors examined whether the reciprocal relationship between alcohol consumption and distress unfolded over time in 2 samples of social drinkers. Participants monitored their alcohol intake and their cognitive and emotional responses to that drinking on hand-held computers. On mornings after drinking, those who had violated their self-imposed limits the day before reported more guilt, even after controlling for acute negative symptoms of drinking and amount consumed. Reciprocally, guilt led to poorer self-regulation of alcohol intake: Greater distress over alcohol consumption was linked to more intake, intoxication, and more limit violations. Individual differences moderated the relationships among limit violations, distress, and drinking. Consistent with the limit violation effect, violating a limit produced distress over consumption among social drinkers, and they responded to that distress by drinking more.

Daily fluctuations in self-control demands and alcohol intake.

Predictions made by the self-control strength model were tested in a sample of underage social drinkers using ecological momentary assessment methodology. On days that participants experienced more self-control demands than average, they were more likely to violate their self-imposed drinking limit after controlling for mood and urge to drink. There was no relationship between self-control demands and urge or intention to drink, nor were self-control demands related to plans to limit drinking. When individuals planned to limit their alcohol intake, they were more affected by self-control demands than when they did not plan to limit their alcohol intake. Trait self-control moderated these relationships. Consistent with the self-control strength model, it appears that exerting self-control in nondrinking areas undermines individuals' capacity to exert self-control of drinking in daily life.

One too many: predicting future alcohol consumption following heavy drinking.

Adult social drinkers used handheld computers to monitor alcohol intake as well as the precursors and consequences of drinking over a 2-week period. The within-person relationship between mood and amount of alcohol consumed was examined, as well as the role of individual differences. When individuals made internal attributions for their greater than average consumption, they were in a more negative mood after drinking. Individuals who experienced a negative mood after drinking consumed more subsequently. This dysregulatory process may help explain the progression from social drinking to more problematic drinking; indeed, the relationship between mood and alcohol intake was stronger for heavier drinkers. Likewise, gender and trait temptation and restriction moderated this process. The results are consistent with the Limit Violation Effect model (R. L. Collins, 1993) of mood and regulation of alcohol intake.

Cue-provoked craving and nicotine replacement therapy in smoking cessation.

Cue exposure paradigms have been used to examine reactivity to smoking cues. However, it is not known whether cue-provoked craving is associated with smoking cessation outcomes or whether cue reactivity can be attenuated by nicotine replacement therapy (NRT) in clinical samples. Cue-provoked craving ratings and reaction time responses were measured on the 1st day of abstinence among 158 smokers who had been randomized to high-dose nicotine (35 mg) or placebo patch. The nicotine patch reduced overall levels of craving but did not attenuate cue-provoked craving increases or reaction time responses. Cue-provoked craving predicted relapse among participants on the nicotine patch but not among those on placebo. In summary, NRT users could benefit from treatment that attenuates cue-provoked craving.

Immediate antecedents of cigarette smoking: an analysis of unrestricted smoking patterns.

Theory suggests that cigarette smoking is under stimulus control and that affect is a key trigger for smoking. A previous study (S. Shiftman et al., 2002) showed little relationship between affect and smoking, but this relationship could have been suppressed by the impact of smoking restrictions. The study evaluated these associations in a 1988 sample that was subject to few smoking restrictions. Smokers (N = 28) not seeking treatment used palmtop computers to record context and affect prior to smoking (n = 2217 observations) and also at random times when not smoking (n = 2,380). Comparisons showed little relationship between smoking and affect. Smoking was associated with particular activities and locations. Urge to smoke was the strongest predictor of smoking. The results replicated the findings of S. Shiffman et al. (2002).

Attentional bias predicts outcome in smoking cessation.

Most attempts to quit smoking end in failure, with many quitters relapsing in the first few days. Responses to smoking-related cues may precipitate relapse. A modified emotional Stroop task-which measures the extent to which smoking-related words disrupt performance on a reaction time (RT) task-was used to index the distracting effects of smoking-related cues. Smokers (N = 158) randomized to a high-dose nicotine patch (35 mg) or placebo patch completed the Stroop task on the 1st day of a quit attempt. Smokers using an active patch exhibited less attentional bias, making fewer errors on smoking-related words. Smokers who showed greater attentional bias (slowed RT on the first block of smoking words) were significantly more likely to lapse in the short-term, even when controlling for self-reported urges at the test session. Attentional bias measures may tap an important component of dependence.

Immediate antecedents of cigarette smoking: an analysis from ecological momentary assessment.

The authors assessed the association between smoking and situational cues, including affect, in real-world contexts. Using ecological momentary assessment, 304 smokers monitored ad-lib smoking for 1 week, recording each cigarette on palm-top computers. Generalized estimating equations contrasted 10,084 smoking and 11,155 nonsmoking situations. After controlling for smoking restrictions, smoking was strongly related to smoking urges and modestly related to consumption of coffee and food, the presence of other smokers, and several activities. Smoking was unrelated to negative or positive affect or to arousal, although it was associated with restlessness. Thus, in daily life, affect appears to exert little influence over ad-lib smoking in heavy smoking adults.

Using self-efficacy judgments to predict characteristics of lapses to smoking.

According to relapse prevention theory, abstinence self-efficacy judgments (ASE; confidence in ability to abstain from smoking) about particular affective and environmental contexts should predict behavior in those contexts. Low-ASE contexts should present challenges to abstinence. In this study, the authors used profile correlations to quantify the relationship between context-specific ASE ratings and the characteristics of lapse episodes. To assess the distinctiveness of this relationship, they also correlated the situations surrounding temptation and randomly selected (nontemptation) episodes with context-specific ASE. The ASE-first lapse profile correlation was significantly greater than zero and significantly greater than ASE-temptation and ASE-nontemptation correlations. This pattern of results remained when multiple lapse episodes were considered. Thus, low-ASE contexts tend to be associated with lapses to smoking.