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PubMed1996

Ambulatory monitoring uncorrected for placebo overestimates long-term antihypertensive action. Systolic Hypertension in Europe (SYST-EUR) Trial Investigators.

This study compares blood pressure (BP) changes during active antihypertensive treatment and placebo as assessed by conventional and ambulatory BP measurement. Older patients (> or = 60 years, n=337) with isolated systolic hypertension by conventional sphygmomanometry at the clinic were randomized to placebo or active treatment consisting of nitrendipine (10 to 40 mg/d), with the possible addition of enalapril (5 to 20 mg/d) and/or hydrochlorothiazide (12.5 to 25 mg/d). At baseline, clinic systolic/diastolic BP averaged 175/86 mm Hg and 24-hour and daytime ambulatory BPs averaged 148/80 and 154/85 mm Hg, respectively. After 13 months (median) of active treatment, clinic BP had dropped by 22.7/7.0 mm Hg and 24-hour and daytime BPs by 10.5/4.5 and 9.7/4.3 mm Hg, respectively (P<.001 for all). However, clinic (9.8/1.6 mm Hg), 24-hour (2.1/1.1 mm Hg), and daytime (2.9/1.0 mm Hg) BPs decreased also during placebo (P<.05, except for daytime diastolic BP); these decreases represented 43%/23%, 20%/24%, and 30%/23% of the corresponding BP fall during active treatment. After subtraction of placebo effects, the net BP reductions during active treatment averaged only 12.9/5.4, 8.3/3.4, and 6.8/3.2 mm Hg for clinic, 24-hour, and daytime BPs, respectively. The effect of active treatment was also subject to diurnal variation (P<.05). Changes during placebo in hourly systolic and diastolic BP means amounted to (median) 21% (range, -1% to 42%) and 25% (-3% to 72%), respectively, of the corresponding changes during active treatment. In conclusion, expressed in millimeters of mercury, the effect of antihypertensive treatment on BP is larger with conventional than with ambulatory measurement. Regardless of whether BP is measured by conventional sphygmomanometry or ambulatory monitoring, a substantial proportion of the long-term BP changes observed during active treatment may be attributed to placebo effects. Thus, ambulatory monitoring uncorrected for placebo or control observations, like conventional sphygmomanometry, overestimates BP responses in clinical trials of long duration.

Aged↗
PubMed1991

Different types of placebo response in patients receiving antidepressants.

OBJECTIVE: The authors studied the responses of drug-treated patients in an attempt to validate observations about abrupt and gradual improvements in patients receiving placebo. Since previous data suggested that in the first 2 weeks of antidepressant treatment specific drug effects are unlikely, the authors hypothesized that this improvement is a placebo effect. Therefore, in the first 2 weeks of antidepressant treatment abrupt and gradual improvements should have the characteristics of their placebo counterparts. METHOD: The subjects were 263 patients in controlled antidepressant trials lasting 6 weeks. RESULTS: The percentage of abrupt improvements that occurred in the first 2 weeks was higher than that for gradual improvements. Abrupt improvements during the first 2 weeks of drug treatment were also less persistent than gradual improvements with drug and no more persistent than improvements with placebo during the same period. However, in weeks 3, 4, and 5, abrupt and gradual improvements with drug were equally persistent and both were more persistent than abrupt improvements with placebo. CONCLUSIONS: These data support the authors' findings about placebo. Abrupt improvements during treatment with both drug and placebo are more likely during the first 2 weeks of treatment and are less likely to persist than gradual improvements. The fact that persistence of abrupt improvements with drug in weeks 1 and 2 appears different from that of gradual improvements but appears no different after week 3 suggests that the mechanism of action of abrupt improvement with drug changes after week 2.

Adolescent↗
PubMed1992

Melancholic/endogenous depression and response to somatic treatment and placebo.

OBJECTIVE: The authors' goals were to examine the effects of somatic treatment and placebo in patients with and without endogenous/melancholic depression. METHOD: Before entry into one of four trials of antidepressant drugs versus placebo, 231 patients were assessed as to whether they met Research Diagnostic Criteria for definite endogenous depression and/or DSM-III criteria for major depressive episode with melancholia. These patients were prospectively assessed for subsequent response to antidepressant treatment or placebo. Previous studies of the effect of endogenous/melancholic depression on treatment response were also reviewed. RESULTS: Of the 76 patients with DSM-III melancholia given active medication, 41 (54%) had a complete or partial response, but only 10 (23%) of the 44 patients with melancholia given placebo had a complete or partial response. Of the 76 depressed patients without melancholia given active medication, 46 (61%) had a complete or partial response, and 15 (43%) of the 35 depressed patients without melancholia given placebo had a complete or partial response. Moderately depressed patients with DSM-III melancholia had a significantly better response to active medication than did severely depressed patients with melancholia and showed the greatest difference between response to active medication and response to placebo. The results of the review of previous studies of the effect of endogenous/melancholic depression on treatment response were mixed. CONCLUSIONS: Depressed patients with melancholia were not particularly different from depressed patients without melancholia in their responses to antidepressant medication but did differ from patients without melancholia in their responses to active medication versus placebo, particularly if their depression was moderate and not severe. This suggests that patients with DSM-III melancholia may be unresponsive to nonsomatic treatments.

Antidepressive Agents↗
PubMed1998

A randomized, placebo-controlled dose-comparison trial of haloperidol for psychosis and disruptive behaviors in Alzheimer's disease.

OBJECTIVE: The goal of this study was to compare the efficacy and side effects of two doses of haloperidol and placebo in the treatment of psychosis and disruptive behaviors in patients with Alzheimer's disease. METHOD: In a 6-week random-assignment, double-blind, placebo-controlled trial (phase A), haloperidol, 2-3 mg/day (standard dose), and haloperidol, 0.50-0.75 mg/day (low dose), were compared in 71 outpatients with Alzheimer's disease. For the subsequent 6-week double-blind crossover phase (phase B), patients taking standard- or low-dose haloperidol were switched to placebo, and patients taking placebo were randomly assigned to standard- or low-dose haloperidol. RESULTS: For the 60 patients who completed phase A, standard-dose haloperidol was efficacious and superior to both low-dose haloperidol and placebo for scores on the Brief Psychiatric Rating Scale psychosis factor and on psychomotor agitation. Response rates according to three sets of criteria were greater with the standard dose (55%-60%) than the low dose (25%-35%) and placebo (25%-30%). The advantage of standard dose over low dose was replicated in phase B. In phase A, extrapyramidal signs tended to be greater with the standard dose than in the other two conditions, primarily because of a subgroup (20%) who developed moderate to severe signs. Low-dose haloperidol did not differ from placebo on any measure of efficacy or side effects. CONCLUSIONS: The results indicated a favorable therapeutic profile for haloperidol in doses of 2-3 mg/day, although a subgroup developed moderate to severe extrapyramidal signs. A starting dose of 1 mg/day with gradual, upward dose titration is recommended. The narrow therapeutic window observed with haloperidol may also apply to other neuroleptics used in Alzheimer's disease patients with psychosis and disruptive behaviors.

Aged↗
PubMed1999

Fluoxetine treatment for depression in patients with HIV and AIDS: a randomized, placebo-controlled trial.

OBJECTIVE: The goals of this study were to determine whether fluoxetine is superior to placebo in treating HIV-seropositive patients with major depression or dysthymia or both, whether severity of immunosuppression is associated with treatment response, and whether fluoxetine treatment is associated with change in immune status as measured by CD4 cell count. METHOD: A double-blind, randomized, placebo-controlled 8-week trial of fluoxetine was conducted in a university-affiliated research outpatient clinic. The fluoxetine-placebo randomization was 2:1. All patients were offered 4 months of additional open treatment. Main outcome measures included the Clinical Global Impression, Hamilton Depression Rating Scale, and CD4 cell count. RESULTS: Of 120 patients randomly assigned to fluoxetine or placebo, 87 completed 8 weeks of treatment. In the total group, 51% had AIDS. All but three were men, 35% were nonwhite, and 6% had intravenous drug use as a risk factor. In an intention-to-treat analysis, 57% of fluoxetine patients and 41% of placebo patients were responders. Among patients who completed the study, 74% responded to fluoxetine and 47% to placebo; this difference was statistically significant. Severity of immunosuppression was not related to antidepressant response, attrition, or side effects, and fluoxetine treatment was not associated with change in CD4 cell count. CONCLUSIONS: Fluoxetine is an effective antidepressant in the context of HIV illness. However, both placebo response and attrition were substantial, suggesting both that nonspecific factors may be more salient and that yet another medication (i.e., an antidepressant) may be less acceptable among patients with serious medical illness already requiring multiple concomitant medications.

Acquired Immunodeficiency Syndrome↗
PubMed2006

A double-blind, randomized, placebo-controlled trial of oxcarbazepine in the treatment of bipolar disorder in children and adolescents.

OBJECTIVE: This multicenter trial examined the efficacy and safety of oxcarbazepine in the treatment of bipolar disorder in children and adolescents. METHOD: A total of 116 outpatients 7 to 18 years of age with bipolar I disorder, manic or mixed, were recruited at 20 centers in the United States and randomly assigned to receive 7 weeks of double-blinded, flexibly dosed treatment with oxcarbazepine (maximum dose 900-2400 mg/day) or placebo. The primary efficacy measure was the mean change from baseline to endpoint in the Young Mania Rating Scale (YMRS), using the last-observation-carried-forward method. RESULTS: Oxcarbazepine (mean dose=1515 mg/day) did not significantly improve YMRS scores at endpoint compared with placebo [adjusted mean change: oxcarbazepine, -10.90 (N=55); placebo, -9.79 (N=55)]. Dizziness, nausea, somnolence, diplopia, fatigue, and rash were each reported in at least 5% of the patients in the oxcarbazepine group with an incidence at least twice that of the placebo group. The majority of adverse events were mild to moderate and occurred during the titration period. Eleven patients (19%) in the oxcarbazepine group discontinued the study because of adverse events, compared with two (4%) in the placebo group. CONCLUSIONS: Oxcarbazepine is not significantly superior to placebo in the treatment of bipolar disorder in youths. While the overall adverse event profile was similar to that reported for patients with epilepsy, the incidence of psychiatric adverse events for both the oxcarbazepine and placebo groups was higher than that reported for the epilepsy population.

Adolescent↗
PubMed2002

Placebo controls in randomized trials of acupuncture.

Considerable intellectual and practical effort has been expended on designing and evaluating placebo controls in acupuncture studies. Somewhat less attention has been paid to the question: Why use a placebo in a randomized trial of acupuncture? This is partly because placebo controls have generally been seen as an inherent part of randomized trial methodology. As a result, most acupuncture trials have included a placebo-control group. A large number of different placebo techniques have been used in these trials. The design and choice of placebo techniques has typically depended on purely theoretical considerations, without empirical validation of physiological inactivity and psychological credibility. Principles can be developed for deciding whether to use placebo or another form of control in a randomized trial. These include issues of ethics, practicality and methodology. Such principles apply regardless of the intervention; they can and should be applied to acupuncture research.

Acupuncture Therapy↗
PubMed2002

Evaluating how placebos produce change. Logical and causal traps and understanding cognitive explanatory mechanisms.

The renewed interest in placebo effects from psychological and methodological angles is manifested in two complementary facets: the causal relationship between placebo effects inside and outside of clinical trials and the continual effort to understand how the underlying mechanisms relate to notions of efficacy and effectiveness. The article challenges the premise that placebo effects can be measured precisely enough that variance attributed to "nonspecific" placebo effects can be hierarchically partitioned from variance attributed to other "more specific" elements of therapy and discusses some of the most important recent developments in the understanding of how placebos produce change through cognitive explanatory mechanisms, including efficacy, outcome, and response expectancies; reverse placebo effects; schemas; and biased-information processing. Although much is already known about the complexity of explanatory mechanisms in placebo and expectancy effects, there is still much to do before establishing causal relationships and developing valid treatments based on this knowledge.

Causality↗
PubMed1980

Effects of placebo versus guanabenz on hypertensive out-patients.

The objectives of this study were two-fold: (1) 1 4-week multicentre, randomized, double-blind efficacy comparison of placebo and guanabenz acetate, a new centrally acting antihypertensive drug, in 168 hypertensive out-patients and (2) a more accurate determination of the incidence of drug-related, non-specific side-effects. Both treatment groups were comparable: 68% female, 63% black, mean age 53 years; 57% mild, 32% moderate, 11% moderately severe hypertensives. Seventy-six placebo patients completed 4 weeks and had a mean supine diastolic blood pressure (SDBP) decrease from 105 to 101 mm Hg (p < 0.01). Seventy-nine guanabenz patients completing 4 weeks had a mean SDBP decrease from 104 to 92 mm Hg (p < 0.01). All of the placebo responses and 10/12 mm Hg of the guanabenz response occurred during Week 1. Clinically significant individual SDBP decreases occurred in thirty-one (41%) placebo and fifty-five (70%) guanabenz-treated patients (p < 0.01). Mean daily guanabenz dose was 24 mg. Drug-related biochemical or electrocardiographic abnormalities were absent. Side-effects of sedation and dry mouth were recorded two and three times more frequently, respectively, in guanabenz as compared to placebo patients. Side-effects usually occurred within Week 1 and diminished in incidence thereafter. Consequently, in these patients it appeared that: (1) guanabenz was an effective, well-tolerated drug, (2) placebo effects on efficacy were significant, occurred early and remained stable, and (3) placebo and guanabenz side-effects were mainly sedation and dry mouth.

Adult↗
PubMed1992

A double-blind, comparative study of zolpidem and placebo in the treatment of insomnia in elderly psychiatric in-patients.

The efficacy and tolerability of the imidazopyridine hypnotic, zolpidem, were investigated in 119 elderly psychiatric in-patients complaining of insomnia in a double-blind, parallel-group, placebo-controlled trial. After a 7-day placebo washout period, patients were randomized to receive 10 or 20 mg/day zolpidem, or placebo for 21 days; thereafter, all patients received placebo for 7 days. Sleep was assessed by patient observation on days 0, 1, 7, 14, 21, 22 and 28. Compared with placebo, 20 mg/day zolpidem significantly improved total duration of sleep between day 0 and day 21, and this was maintained at day 28. After 10 or 20 mg/day zolpidem, there was also a trend towards improvement in all other sleep parameters, which remained above baseline at day 28. Zolpidem was well tolerated with no withdrawal symptoms during the second 7-day placebo treatment period. Daytime drowsiness was reported in three patients receiving 20 mg/day zolpidem and in one receiving 10 mg/day zolpidem, but there was no significant increase in daytime drowsiness between days 0 and 21. Ataxia occurred in two, one and one patient, respectively, treated with 20 mg/day zolpidem, 10 mg/day zolpidem and placebo. The incidences of other adverse events or effects on clinical and laboratory parameters were minimal and similar in all three treatment groups. It is concluded that, in elderly psychiatric patients, 10 mg/day zolpidem can be used to treat insomnia and can be safely added to concomitant psychotropic treatment without inducing daytime drowsiness.

Aged↗
PubMed2003

Correlates of therapeutic response in panic disorder presenting with palpitations: heart rate variability, sleep, and placebo effect.

OBJECTIVE: To examine the correlates of therapeutic response of patients with panic disorder presenting with palpitations, we hypothesized that therapeutic response would correlate with heart rate variability (HRV) and sleep measures. METHODS: After a 1-week placebo washout, 27 patients free of structural heart disease and not on cardioactive drugs were randomized in a double-blinded fashion to 4 weeks of treatment with clonazepam (a known antipanic agent) or placebo. We performed standard sleep measures and recorded HRV from 24-hour Holter acquisitions at baseline and end of study. We defined response to therapy as a 50% improvement in the Hamilton Anxiety Rating Scale (HARS) score, confirmed by questionnaires and reaction to sodium lactate infusion. RESULTS: There were 12 responders and 15 nonresponders. Normalization of sleep pattern (including less stage 1 and rapid eye movement [REM] sleep) was observed in both drug and placebo responders (P = 0.011 and P = 0.05, respectively) and in placebo responders alone, compared with nonresponders (P = 0.006 and P = 0.013, respectively). Placebo responders were more likely to show less depression, but even after we controlled for depression, main sleep effects remained. None of the HRV measures correlated with response, but compared with placebo, clonazepam led to a decrease in all the time and frequency domain measures of HRV (all P < 0.05). CONCLUSIONS: Central mechanisms are related to the therapeutic response of patients with panic disorder presenting with palpitations, but this does not directly correlate with HRV. Larger and longer studies may allow objective explanations of placebo response in panic disorder.

Adolescent↗
PubMed2002

HR (Paroven, Venoruton; 0-(beta-hydroxyethyl)-rutosides) in venous hypertensive microangiopathy: a prospective, placebo-controlled, randomized trial.

UNLABELLED: The aim of this study was to demonstrate whether HR (Paroven-Venoruton; 0-(beta-hydroxyethyl)-rutosides), was effective in improving the microcirculation in venous hypertension and microangiopathy. Sixty patients with severe venous hypertension due to chronic venous insufficiency, ankle swelling, and lipodermatosclerosis were included. After informed consent, patients were randomized into a treatment group and a placebo group. Patients in the treatment group received oral HR (2 g/day for 8 weeks); those in the placebo group received a comparable placebo. RESULTS: The two groups were comparable for age and sex distribution. The mean age was 45 years (SD 9) in the treatment group (31 patients) and 45.5 (SD 10) in the placebo group (29 patients). There were no differences between the placebo and treatment groups at inclusion. There was no change between inclusion and measurements at 8 weeks in the placebo group. A significant decrease (P < 0.05) in flux at rest and rate of ankle swelling was observed in the treatment group. The decrease in capillary filtration was associated with improvement in signs and symptoms (P < 0.05). The difference in flux, sign and symptoms, and filtration was clinically important at 8 weeks in the treatment group when compared with the placebo group. No adverse effects were observed. CONCLUSION: Venous microangiopathy was improved by HR treatment.

Adult↗
PubMed2005

The efficacy of tadalafil in improving sexual satisfaction and overall satisfaction in men with mild, moderate, and severe erectile dysfunction: a retrospective pooled analysis of data from randomized, placebo-controlled clinical trials.

BACKGROUND: Satisfaction with the sexual experience is considered important when evaluating the impact of treatments for erectile dysfunction (ED), yet satisfaction has been infrequently assessed in clinical trials. OBJECTIVE: To evaluate satisfaction with, and enjoyment of, the sexual experience in men with ED enrolled in 11 placebo-controlled clinical trials of tadalafil. STUDY DESIGN AND METHODS: Retrospective pooled analysis of data from 11 randomized, double blind, placebo-controlled clinical trials of tadalafil. Men with mild (N = 838), moderate (N = 558), or severe (N = 703) ED who were randomized to tadalafil 10 mg or 20 mg or placebo taken as needed for 12 weeks were included in this analysis. Efficacy measures included the International Index of Erectile Function (IIEF). Reported herein are the scores on the IIEF overall satisfaction domain and individual IIEF questions (IIEF-Q7, satisfaction with intercourse; and IIEF-Q8, enjoyment of intercourse). RESULTS: At least moderate satisfaction (IIEF overall satisfaction domain) was reported by 55% and 72% of patients with mild ED taking tadalafil 10 mg and 20 mg, respectively, compared with 33% taking placebo (p < 0.002); 60% and 65% vs. 19% of patients with moderate ED (p < 0.001); and 32% and 49% vs. 9% with severe ED (p < 0.001). Satisfactory intercourse during most attempts or almost always/always (IIEF-Q7) was reported by 59% and 79% of patients with mild ED taking tadalafil 10 mg and 20 mg vs. 32% taking placebo (p < 0.001); 52% and 65% vs. 18% with moderate ED (p < 0.001); and 28% and 49% vs. 5% with severe ED (p < 0.001). Highly or very highly enjoyable intercourse (IIEF-Q8) was reported by 45% and 63% of patients with mild ED taking tadalafil 10 mg and 20 mg vs. 21% taking placebo (p < 0.001); 43% and 56% vs. 16% with moderate ED (p < 0.001); and 19% and 44% vs. 5% with severe ED (p < 0.001). CONCLUSIONS: Compared with placebo, tadalafil 10 mg and 20 mg improved overall satisfaction with the sexual experience, intercourse satisfaction, and intercourse enjoyment in men with mild, moderate, and severe ED.

Adult↗
PubMed2006

The impact of migraine on daily activities: effect of topiramate compared with placebo.

OBJECTIVE: Assess the impact of migraine preventive therapy on patient-reported routine daily activities using the Migraine Specific Questionnaire (MSQ) and the Medical Outcomes Study Short Form-36 (SF-36) in patients with migraine who participated in a 26-week, randomized, double-blind, placebo-controlled trial of topiramate for migraine prevention. METHODS: Patients were required to have 3-12 migraines and < or = 15 headache days/month during the baseline phase. Patients who failed > 2 adequate regimens of migraine preventive therapy were excluded. MSQ and SF-36 data were collected at baseline, weeks 8, 16, and 26 from 469 patients receiving either topiramate 50, 100, or 200 mg/day or placebo. Patients entered a double-blind, 8-week titration period followed by an 18-week maintenance period. Two activity-related MSQ domains (Role Restrictive [RR] and Role Prevention [RP]) and two activity-related SF-36 domains (Role Physical [SF-36-RP] and Vitality [SF-36-VT]) were prospectively designated as the outcome measures. Changes in MSQ and SF-36 scores during the double-blind phase relative to prospective baseline scores were compared between topiramate- and placebo-treated groups. Specifically, a mixed-effect piecewise linear regression model was used to estimate average domain score over time, and areas under the domain-over-time curve (AUC) were compared using a 2-sided t-test, with multiplicity adjustment. RESULTS: In the intent-to-treat population (N = 469), topiramate (all doses) significantly improved mean MSQ-RR domain scores versus placebo (topiramate 50 mg/day, p = 0.035; topiramate 100 mg/day; p < 0.001; topiramate 200 mg/day, p = 0.001). Topiramate-associated improvements in mean MSQ-RP domain scores were significant versus placebo only for topiramate 100 mg/day (p = 0.045). SF-36-RP and SF-36-VT domain scores improved (not significant versus placebo) for topiramate 100 and 200 mg/day. Changes in these MSQ and SF-36 domain scores significantly correlated with changes in mean monthly migraine frequency. CONCLUSION: Improvements in patient-reported outcomes specific for migraine (measured by the MSQ) were significantly better for patients receiving topiramate than for those receiving placebo. Improvements in the prospectively selected MSQ and SF-36 domains were significantly correlated with the decrease in mean monthly migraine frequency observed with topiramate treatment.

Activities of Daily Living↗
PubMed1986

Comparison of controlled-release diazepam capsules and placebo in patients in general practice.

A multi-centre, randomized double-blind parallel study was carried out to compare the efficacy and tolerance of a single daily dose of controlled-release (CR) capsules of diazepam (10 mg and 15 mg) with placebo under conditions close to those of general practice. All patients between 16 and 60 years of age, presenting an anxiety syndrome as a result of neurotic disturbance, for whom benzodiazepine treatment was indicated for at least 3 weeks, were accepted for the study. The results from 231 patients (119 on placebo, 55 on 10 mg and 57 on 15 mg diazepam) were analyzed after 1 and 3 weeks of treatment. Complaints were found to have improved after 1 week and 3 weeks in the controlled-release diazepam groups whereas the corresponding results with placebo were clearly less favourable. After 1 week, and even more strikingly after 3 weeks, evaluation of the general effects of treatment showed better results with diazepam than with placebo. The obviously higher rate of drop-outs on placebo confirmed its less reliable effect. The controlled-release capsules were well tolerated and notably better than placebo. The most frequent side-effect reported on diazepam was fatigue, and this was probably due to a relative overdosage from use of a standardized dose throughout treatment. Other reported side-effects could not definitely be ascribed to the drug. At the end of a week, successful results were achieved in 48.2% of the patients on controlled-release diazepam compared with only 14.3% of those on placebo. After 3 weeks, these figures were 73.2% and 30.3%, respectively.

Adolescent↗
PubMed2005

Trick or treat: the effect of placebo on the power of pharmacogenetic association studies.

The genetic mapping of drug-response traits is often characterised by a poor signal-to-noise ratio that is placebo related and which distinguishes pharmacogenetic association studies from classical case-control studies for disease susceptibility. The goal of this study was to evaluate the statistical power of candidate gene association studies under different pharmacogenetic scenarios, with special emphasis on the placebo effect. Genotype/phenotype data were simulated, mimicking samples from clinical trials, and response to the drug was modelled as a binary trait. Association was evaluated by a logistic regression model. Statistical power was estimated as a function of the number of single nucleotide polymorphisms (SNPs) genotyped, the frequency of the placebo 'response', the genotype relative risk (GRR) of the response polymorphism, the strategy for selecting SNPs for genotyping, the number of individuals in the trial and the ratio of placebo-treated to drug-treated patients. We show that: (i) the placebo 'response' strongly affects the statistical power of association studies--even a highly penetrant drug-response allele requires at least a 500-patient trial in order to reach 80 per cent power, several-fold more than the value estimated by standard tools that are not calibrated to pharmacogenetics; (ii) the power of a pharmacogenetic association study depends primarily on the penetrance of the response genotype and, when this penetrance is fixed, power decreases for larger placebo effects; (iii) power is dramatically increased when adding markers; (iv) an optimal study design includes a similar number of placebo- and drug-treated patients; and (v) in this setting, straightforward haplotype analysis does not seem to have an advantage over single marker analysis.

Clinical Trials as Topic↗
PubMed2005

Efficacy and safety analysis of epoetin alfa in patients with small-cell lung cancer: a randomized, double-blind, placebo-controlled trial.

PURPOSE: This randomized, double-blind, placebo-controlled trial (N93-004) evaluated the effects of epoetin alfa on tumor response to chemotherapy and survival in patients with small-cell lung cancer (SCLC). PATIENTS AND METHODS: Adult patients with hemoglobin < or = 14.5 g/dL starting chemotherapy received epoetin alfa 150 U/kg or placebo subcutaneously 3 times weekly until 3 weeks after completion of chemotherapy. Survival was assessed for 3 years. The primary end point was the proportion of patients with complete or partial response after three chemotherapy cycles. RESULTS: The trial was terminated prematurely after 224 of a projected 400 patients were accrued. Baseline characteristics were similar between groups. Epoetin alfa and placebo patients (n = 109 and n = 115, respectively) had mean baseline hemoglobin of 12.8 g/dL and 13.0 g/dL, respectively. Overall tumor response was similar between the epoetin alfa and placebo groups after three chemotherapy cycles (72% and 67%, respectively; 95% CI of difference, -6% to 18%) and after completion of chemotherapy (60% and 56%, respectively; 95% CI of difference, -9% to 17%). Epoetin alfa and placebo groups had similar median overall survival (10.5 and 10.4 months, respectively) and overall mortality (91.7% and 87.8%, respectively; hazard ratio, 1.172; 95% CI, 0.887 to 1.549; P = .264). Hemoglobin was maintained in the prechemotherapy range in epoetin alfa patients, but decreased substantially in placebo patients. Fewer epoetin alfa patients than placebo patients required transfusion. CONCLUSION: These results suggest that in newly diagnosed patients with SCLC epoetin alfa does not affect tumor response to chemotherapy or survival. However, the early trial closure makes these conclusions preliminary.

Adult↗
PubMed2005

A randomized, placebo-controlled GH trial in very preterm infants who were at risk for bronchopulmonary dysplasia and were treated with dexamethasone.

Very preterm infants who develop bronchopulmonary dysplasia are often treated with dexamethasone (DEXA) to wean them from the ventilator. As DEXA has growth-suppressive and catabolic effects, which might have long-term consequences on growth and organ development, we investigated whether high-dose GH treatment could overcome these effects. In a randomized, double-blind, placebo-controlled trial, 30 ventilated very low birth weight infants were assigned to receive either GH or placebo treatment after start of DEXA. DEXA was given for 24 d (starting dose 0.5 mg . kg(-1) . d(-1), tapering off every third day). Simultaneously, high-dose GH (0.3 mg . kg(-1) . d(-1)) or placebo was administered during 6 wk. During high-dose DEXA treatment (dose 0.5-0.3 mg . kg(-1) . d(-1)), no gain in head circumference, weight, crown-heel length, and knee-heel length occurred in the GH and placebo groups. Growth during the 6-wk study period was not different between the GH and the placebo groups. Two patients in the placebo group died, but the number and the severity of adverse effects was not statistically different between the GH and placebo groups. In conclusion, high-dose GH treatment did not improve growth in DEXA-treated very preterm infants and thus cannot be recommended to prevent growth failure in these infants. During high-dose DEXA, a complete growth arrest occurred, including stunting of head growth. Growth in head circumference and weight with lower dose DEXA was comparable to growth after discontinuation of DEXA.

Anti-Inflammatory Agents↗