1. L.S. Remy1, G. Woody2, K. Lynch2, K. M. Kampman2
A reduction in cocaine use during a topiramate clinical trial among cocaine and alcohol dependent participants predicted better scores on the SF-36 for quality of life after treatment.
L.S. Remy1, G. Woody2, K. Lynch2, K. M. Kampman2
Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil1, Perelman School of Medicine at the University of Pennsylvania2
Abstract
Short Form 36 Health Survey
Vitality and General Health vs. Abstinent Weeks
Background: Determining a successful outcome in cocaine pharmacotherapy trials is a topic of great interest. While abstinence is clearly preferred, it is often difficult to achieve. However, a significant reduction in cocaine use may be clinically meaningful, as seen in alcohol studies where a reduction in alcohol use has been associated with significant improvements in health and quality of life (1). This secondary analysis addresses this issue by examining improvement in health-related quality of life associated with reductions in cocaine use in a 12-week clinical trial of topiramate for treatment of cocaine dependence using results from the Short Form-36 Health Status Questionnaire (SF-36).
Methods: These data were drawn from a 12–week double blind placebo controlled trial of topiramate for comorbid cocaine and alcohol dependence involving 170 subjects. All subjects were abstinent from cocaine prior to randomization long enough to submit a benzoylecgonine–negative urine sample on the day of randomization. Subjects were titrated to a dose of 300 mg of topiramate daily over 6 weeks. Urine drug screens were obtained three times weekly. Subjects completed the SF 36 at baseline and at 12 weeks. The clinical measures used in these analyses included the number of cocaine-abstinent weeks based on self-report and UDS tests, and the SF-36. To test association between changes in SF-36 scales and these measures, separate regression models predicting end-of-treatment SF-36 scales from the baseline version of the Sf-36 scale and the clinical measures were used. A binary factor for topiramate was included as a main effect, and topiramate interactions with the clinical measures were also examined.
Results: There were no significant interactions between treatment group and changes in sf 36 scale scores from baseline to end of medication phase. Higher cocaine-abstinent weeks in both treatment groups were associated with greater improvements in the SF 36 scales at the end of the medication phase of the trial compared to baseline. However, results were only statistically significant for the General Health Scale, Vitality Scale, Social Functioning Scale, and Mental Health Scale. Subgroup analysis of the results suggested that much of the benefit of cocaine-abstinent weeks was drawn from subjects who were abstinent for almost the entire medication phase of the trial.
Conclusion: In this trial, reductions in cocaine use were associated with significant improvement in health related quality of life. However most of the improvement was found in subjects who were abstinent for almost the entire duration of the trial. This outcome does not support a reduction in cocaine use short of complete abstinence as a clinically meaningful outcome for cocaine pharmacotherapy trials.
This trial was funded by Grant support was provided from the National Institute on Drug Abuse P60-DA , P50 DA012756, U54DA and T32 MH
36-item, patient-reported survey of patient health
Good reliability and validity (2)
The SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability (4)
The eight scales include:
vitality
physical functioning
bodily pain
general health perceptions
physical role functioning
emotional role functioning
social role functioning
mental health
The instruments asks about feelings and functioning over the past week.
Regression Adjusted End of Study Scale Scores vs. Abstinent Weeks
Vitality
General Health
Regression adjusted end of study scale scores for the Vitality Scale and the General Health Scale vs. number of abstinent weeks. Scores tended to increase with the number of abstinent weeks with the highest scores generally associated with subjects who maintained abstinence for most of the 12 weeks of the trial .
Background
Abstinent Weeks and SF-36 Scale Scores
S R Functioning and Mental Health vs. Abstinent weeks
Determining a successful outcome in cocaine pharmacotherapy trials is a topic of significant interest. The FDA’s Center for Drug Evaluation and Research (CDER) provides specific guidance to the research and pharmaceutical communities regarding the selection of endpoints for use in clinical trials. Assessment tools used in clinical trials should have strong psychometric properties. In addition, patient reported measures of symptoms and level of functioning are considered useful as they may provide meaningful evidence of benefit from treatment for stimulant use. However, there is a lack of consensus regarding the validity of patient-reported drug use, drug-related symptoms and problems. At this time, sustained abstinence is considered the only outcome accepted by the US Food and Drug Administration (FDA) as a valid endpoint for clinical trials evaluating pharmacotherapies for drug use disorders (2). This outcome is difficult to achieve and it is possible that reductions in cocaine use, short of complete abstinence, may result in clinically meaningful improvements in patient symptoms and level of functioning. In trials evaluating medications for the treatment of alcohol use disorder reductions in drinking, particularly reductions in heavy drinking days were associated with fewer alcohol-related consequences and lower levels of drinking during a 1-year follow-up period (1). So far, no cocaine pharmacotherapy trials have shown that reductions in cocaine use have been associated with similar measurable improvements in cocaine related problems. This trial was intended to evaluate whether reductions in cocaine use (but not complete abstinence from cocaine) resulted in clinically meaningful improvement in patient reported symptoms and level of functioning using a valid and reliable measure of health related quality of life, the Short Form 36 Health Survey (3).
Regression Adjusted End of Study Scale Scores vs. Abstinent Weeks
Scale
Chi Square p
Physical Functioning
1.2
.28
Bodily Pain
2.8
.09
Physical Role Functioning
3.4
.07
Emotional Role Functioning
6.7
.01
Vitality
10.4
.001
Mental Health
11.1
.0008
Social Role Functioning
12.6
.0004
General Health
23.2
<.0001
Social Role Functioning
Mental Health
Separate regression models predicting end of medication phase SF36 Scale scores for each scale including baseline scale score and number of abstinent weeks. Significant associations between abstinent weeks and scale scores were noted for Vitality, Mental Health, Social Role Functioning and General Health.
Regression adjusted end of study scale scores for the Social Role Functioning Scale and the Mental Health Scales vs. number of abstinent weeks. Scores tended to increase with the number of abstinent weeks with the highest scores generally associated with subjects who maintained abstinence for most of the 12 weeks of the trial
Subgroup analysis
Methods
Conclusions .
Reductions in cocaine use were associated with significant improvement in health related quality of life as measured by the SF 36
SF 36 scales that declined significantly included the Vitality Scale, the Mental Health Scale, the Social Role Functioning Scale, and the General Health Scale
Subgroup analysis suggested that most of the improvement in SF 36 Scale scores occurred in subjects abstinent from cocaine for most of the trial
These results suggest that reductions in cocaine use short of complete abstinence did not show significant improvements in patient symptoms and level of functioning as measured by the SF 36 during this 12 week trial.
Subjects
170 psychiatrically and medically stable, DSM-IV cocaine and alcohol dependent men and women ages 18-70
In the past 30 days, used no less than $200-worth of cocaine.
Drank within 30 days of intake day, reported a minimum of 48 standard alcoholic drinks (avg. 12 drinks/wk) for women and 60 standard drinks(15 drinks per week) for men in a consecutive 30-day period over the 90-day period prior to starting intake, and had 2 or more days of heavy drinking (defined as 5 or more drinks per day in males and 4 or more drinks per day in females) in this same pre-treatment period.
Procedures
Subjects were required to submit a benzoylecgonine (BE) negative urine on the day of randomization
300 mg of topiramate (titrated over 6 weeks) or matching placebo,
12 weeks of medication
Weekly medication management sessions plus an hour-long cognitive behavioral therapy sessions
Three urine drug screens collected weekly
Self-reported cocaine use measured by timeline follow back
Outcome Measures
Each study week was coded as cocaine-abstinent or not abstinent based on the following definition: a study week was coded as an abstinent week if the participant reported no cocaine use during the study week, and provided at least two negative and no BE-positive urine drug screen samples during the study week.
The SF 36 was administered at baseline and at the end of the medication phase of the trial
12 weeks
11 weeks
10 weeks
8 weeks
Scale Χ2 p
Vitality
14.9
.0001
19.1
<.0001
13.3
.0003
5.7
.02
Mental Health
10.5
.0012
5.6
.018
4.3
.0374
2.2
.13
Social Role
Functioning
9.4
.0021
11.9
.0006
8.3
.004
.04
General Health
14.3
.0002
9.8
6.0
.014
3.1
.07
Disclosures
None of the authors reported a conflict of interest.
References
Rerunning the original regressions excluding subjects with progressively fewer abstinent weeks suggest that the majority of the change in SF 36 scores occurred in subjects who were abstinent for all or most of the trial. .
1. Falk, D., Wang, X.Q., Liu, L., et al., Percentage of subjects with no heavy drinking days: evaluation as an efficacy endpoint for alcohol clinical trials. Alcohol. Clin. Exp.Res. 34, 2022–2034.
2. Kulik, BD, Carroll, KM, Duhig, A, et al. Measures of outcome for stimulant trials: ACTTION recommendations and research agenda. Drug Alcohol Depend Jan 1;158:1-7.
3. McHorney CA, Ware JE Jr, Lu JF, et al. The MOS 36-item Short-Form Health Survey (SF-36): III. Tests of data quality, scaling assumptions, and reliability across diverse patient groups. Med Care Jan;32(1):40-66.
4. SF 36 detailed scoring