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At least 865 records · Page 48Linked to original sources
PubMed1987

Baseline characteristics of 10-day placebo washout responders in antidepressant trials.

In antidepressant drug trials, the randomized treatment phase is usually preceded by a single-blind placebo period or "washout." Ninety-four depressed patients who improved during this 10-day placebo period constitute our study focus. Analysis of baseline and postplacebo measures showed that the 10-day placebo responders in our sample were convincingly depressed at baseline and improved significantly after placebo washout. This group of patients differed from 6-week placebo responders in our randomized trials in being more mildly ill, being more chronic, containing fewer cases of primary depression, and having fewer illness precipitants. They differed from placebo nonresponders largely in manifesting milder illness symptoms across the range of psychopathology. The proportion of placebo washout responders declined in the winter months.

Adolescent↗
PubMed1987

Objective changes in intrauterine pressure during placebo treatment of dysmenorrhea.

The paradoxical improvement of many subjective phenomena during placebo therapy is both well established and notorious for confounding many well designed studies. Consistently high placebo response rates of as much as 44% have been reported in subjective studies of dysmenorrhea. In an effort to evaluate the discordant role of objective uterine activity known to be associated with primary dysmenorrhea and the subjective sensation of discomfort, data from 18 patients undergoing meclofenamate therapy for primary dysmenorrhea were evaluated. In this study both the sum of pain intensity differences (SPID) and the total pain relief scores at each study time (TOTPAR) showed increases during both drug and placebo therapy with statistically significant differences favoring drug therapy. Ten percent of patients eventually reported 'complete relief' during placebo therapy. In contrast to this subjective placebo response, objective measures of intrauterine pressure showed consistent worsening in 13 out of 14 pressure parameters with 25% of patients experiencing a 2-fold or greater increase in the number of contractions while on placebo therapy. The ability to document unchanged or worsening objective parameters associated with the development of 'pain' in the face of reported subjective improvements may provide new insight into the mechanisms by which the 'placebo effect' occurs.

Clinical Trials as Topic↗
PubMed1989

Conditioned response models of placebo phenomena: further support.

Following our earlier research, we further investigated a model that conceptualizes placebo phenomena as the result of conditioning and attempted to extend and replicate the finding that placebo responses can be conditioned in human subjects. Two groups of 10 subjects were told that they were receiving an analgesic which was in fact a placebo. During the conditioning, placebo administration was surreptitiously paired with an increase in the painful stimulus for half of the subjects and with a decrease for the other half. Subjects were tested pre and post conditioning for a placebo response. A second type of experimental pain was also used to determine stimulus generalization. The results confirmed a previous finding that placebo responses can be conditioned in human subjects. The implications for clinical practice of a learning model of placebo behavior are discussed.

Adult↗
PubMed1993

Is TENS purely a placebo effect? A controlled study on chronic low back pain.

Although high-frequency low-intensity transcutaneous electric nerve stimulation (TENS) has been extensively used to relieve low back pain, experimental studies of its effectiveness have yielded contradictory findings mainly due to methodological problems in pain evaluation and placebo control. In the present study, separate visual analog scales (VAS) were used to measure the sensory-discriminative and motivational-affective components of low back pain. Forty-two subjects were randomly assigned to 1 of 3 groups: TENS, placebo-TENS, and no treatment (control). In order to measure the short-term effect of TENS, VAS pain ratings were taken before and after each treatment session. Also, to measure long-term effects, patients rated their pain at home every 2 h throughout a 3-day period before and 1 week, 3 months and 6 months after the treatment sessions. In comparing the pain evaluations made immediately before and after each treatment session, TENS and placebo-TENS significantly reduced both the intensity and unpleasantness of chronic low back pain. TENS was significantly more efficient than placebo-TENS in reducing pain intensity but not pain unpleasantness. TENS also produced a significant additive effect over repetitive treatment sessions for pain intensity and relative pain unpleasantness. This additive effect was not found for placebo-TENS. When evaluated at home, pain intensity was significantly reduced more by TENS than placebo-TENS 1 week after the end of treatment, but not 3 months and 6 months later. At home evaluation of pain unpleasantness in the TENS group was never different from the placebo-TENS group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1995

Limitations of head-up tilt test for evaluating the efficacy of therapeutic interventions in patients with vasovagal syncope: results of a controlled study of etilefrine versus placebo.

OBJECTIVES: This study assessed the efficacy of oral etilefrine (10 mg three times a day) in preventing a positive response to head-up tilt testing. BACKGROUND: Previous reports have suggested that oral etilefrine can be effective either in preventing a positive response to head-up tilt testing or in reducing syncopal recurrences in patients with vasovagal syncope. Up to now most studies assessing drug therapy in these patients have been uncontrolled. METHODS: This was a randomized double-blind crossover study of etilefrine versus placebo in 30 consecutive patients with syncope and a baseline positive head-up tilt test. After the first test, patients had no treatment for 3 days and were randomized to receive etilefrine or placebo for 4 additional days. They underwent tilt testing under treatment and again after 3 days of washout; they then received the alternative treatment for 4 days, and a third test was performed. RESULTS: Head-up tilt test results were negative in 13 (43%) patients with etilefrine and 15 (50%) with placebo (p = NS). Therefore, the statistical power of the study was only 10%. The rate of positive responses decreased with repeated testing irrespective of the assigned treatment: A positive response was obtained during the second head-up tilt test in 20 patients (10 with placebo, 10 with etilefrine) but in only 12 during the third (7 with etilefrine, 5 with placebo) (p < 0.05). CONCLUSIONS: Oral etilefrine (10 mg three times a day) was not superior to placebo in preventing a positive response to head-up tilt testing. Despite a low statistical power, the high rate of negative response with placebo (50%) suggests that controlled trials are needed to assess the real efficacy of any treatment in patients with vasovagal syncope.

Administration, Oral↗
PubMed1996

Vitamin C, the placebo effect, and the common cold: a case study of how preconceptions influence the analysis of results.

A large number of placebo-controlled studies have shown that vitamin C supplementation alleviates the symptoms of the common cold, but widespread skepticism that vitamin C could have any significant effect remains. One of the most influential common cold studies, published in 1975, was carried out by Thomas Karlowski et al, at the National Institutes of Health. Their placebo consisted of lactose, which can easily be distinguished from ascorbic acid by taste. Karlowski et al, found a 17% decrease in the duration of cold episodes in the group administered vitamin C (6 g/day); however, they suggested that the decrease was entirely due to the placebo effect. In this article it will be shown that the placebo effect is not a valid explanation for the results of the Karlowski study, as it is inconsistent with their results. This is an important conclusion for two reasons. First, the placebo explanation becomes even more unreasonable as regards the reported benefits found in several other studies with valid placebo tablets. Second, as the results from the Karlowski study are not due to the placebo effect, their results can be used to assess the quantitative effects of vitamin C supplementation. The most important conclusions from Karlowski's study are that therapeutic vitamin C supplementation during a common cold episode appears to be as effective as regular supplementation, and that there appears to be linear dose dependency at least up to 6 g/day. These findings suggest that large therapeutic vitamin C doses might alleviate the symptoms of the common cold substantially.

Ascorbic Acid↗
PubMedDate not supplied

A double-blind, placebo-controlled pilot study examining the effectiveness of intravenous ondansetron in the prevention of postoperative nausea and emesis.

STUDY OBJECTIVE: To compare the efficacy and safety profiles of ondansetron and a placebo when infused immediately prior to anesthesia induction for the prevention of postoperative nausea and emesis (vomiting or retching). DESIGN: Randomized, double-blind, placebo-controlled, parallel, multicenter pilot study. SETTING: Three U.S. ambulatory surgical facilities. PATIENTS: One hundred eighty ASA physical status I and II women scheduled to undergo ambulatory gynecologic surgical procedures while receiving general endotracheal anesthesia. INTERVENTIONS: Ondansetron 8 mg or a placebo (equivalent volume) was given intravenously (IV) prior to anesthesia induction to prevent postoperative nausea and vomiting. MEASUREMENTS AND MAIN RESULTS: For the first 24 hours following emergency from anesthesia, patients were monitored in the postanesthesia care unit by a research observer and at home via telephone contact and diary cards. More patients in the ondansetron group (62%) than in the placebo group (40%) were emesis-free over the 24-hour study period (p = 0.005). Ondansetron also was more efficacious than the placebo over the 24-hour study period when a surgery duration of more than 45 minutes was considered in the analyses. For all patients, regardless of surgery duration, there was a low degree of nausea during the course of the study. In all instances, the degree of nausea was slightly lower for ondansetron-treated patients than for placebo-treated patients; however, in no instances were the differences statistically significant. Ondansetron and placebo had similar safety profiles as established by laboratory test results, vital sign monitoring, and adverse event reporting. CONCLUSION: Ondansetron, infused IV before anesthesia induction, appears to be safe and effective when used in the prevention of postoperative nausea and emesis.

Adult↗
PubMed2006

Onset of action of fexofenadine hydrochloride 60 mg/pseudoephedrine hydrochloride 120 mg in subjects aged 12 years with moderate to severe seasonal allergic rhinitis: a pooled analysis of two single-dose, randomized, double-blind, placebo-controlled allergen exposure unit studies.

BACKGROUND: The onset of action of antihistamine-decongestant combinations is an important factor in the treatment of subjects with seasonal allergic rhinitis (SAR). OBJECTIVE: This was a pooled analysis of 2 published studies with identical designs investigating the onset of action of the combination of fexofenadine hydrochloride 60 mg/pseudoephedrine hydrochloride 120 mg (FEX60/PSE120) in subjects with moderate to severe SAR. METHODS: Subjects aged 12 years received single doses of FEX60/PSE120 or placebo in 2 randomized, double-blind, placebo-controlled, parallel-group, allergen exposure unit studies and recorded their SAR symptoms on diary cards before dosing, at 15-minute intervals for 2 hours after dosing, and at 30-minute intervals for the next 4 hours. The primary efficacy end point was onset of action, assessed in terms of absolute change in the major symptom complex (MSC) score, which was the sum of scores for the individual symptoms of stuffy nose, itchy nose, runny nose, watery eyes, itchy eyes, itchy ears/throat, and sneezing. Secondary end points included the absolute and percent change in the total symptom complex (TSC) score (the sum of the MSC score plus the scores for nose blowing, sniffles, postnasal drip, and cough) and individual symptom scores. Treatment-emergent adverse events (TEAEs) were recorded. Analyses were performed on the modified intention-to-treat (mITT) population, which included all subjects who were randomized to treatment and took the single dose of study medication according to the protocol. RESULTS: A total of 1693 subjects were screened in the 2 studies, and 786 were randomized (298 in study 1, 488 in study 2). Two subjects withdrew from study 2; therefore, the mITT population consisted of 784 subjects. Subjects' mean age was 33.4 years, and 64.4% were female. The onset of action of FEX60/PSE120 was 45 minutes; the least squares mean (SD) treatment difference in the change from baseline in absolute MSC score was 0.8 (0.31) (95% CI, 0.2-1.4; P = 0.008). All subsequent changes from baseline in MSC scores were statistically significant for FEX60/PSE120 compared with placebo (P < 0.001). The absolute and percent change in TSC score and the percent change in MSC score were significantly decreased at all time points from 45 minutes after dosing for FEX60/PSE120 compared with placebo (all, P < 0.05). Individual symptoms (mean of hours 1 to 5) also were significantly improved with FEX60/PSE120 compared with placebo (all, P < 0.05). TEAEs were reported by 2.3% (9/391) and 4.3% (17/393) of subjects receiving FEX60/PSE120 and placebo, respectively. The most commonly occurring TEAS in the FEX60/PSE120 and placebo groups was somnolence (n = 4 and n = 6, respectively). CONCLUSION: In this pooled analysis of 2 allergen exposure unit studies, FEX60/PSE120 had an onset of action of 45 minutes and a sustained effect throughout the 6-hour study period in subjects with moderate to severe SAR.

Adult↗
PubMed2004

Oxcarbazepine in painful diabetic neuropathy: a randomized, placebo-controlled study.

In this multicentre, placebo-controlled, 16-week trial, the efficacy and safety of oxcarbazepine monotherapy in patients with neuropathic pain of diabetic origin was evaluated. Eligible patients had a 6-month to 5-year history of neuropathic pain symptoms of diabetic origin and a pain rating of > or =50 units on the visual analogue scale (VAS). Oxcarbazepine was initiated at a dose of 300 mg/day and titrated to a maximum dose of 1800 mg/day. In total, 146 patients (oxcarbazepine, n=69; placebo, n=77) were randomized. After 16 weeks, oxcarbazepine-treated patients experienced a significantly larger decrease in the average change in VAS score from baseline compared with placebo (-24.3 vs. -14.7 units, respectively; p=0.01). The reduction from baseline in mean VAS score for oxcarbazepine-treated patients was of a greater magnitude than placebo as early as week 2 (-8.0 vs. -4.7; p<0.05). A significantly greater proportion of oxcarbazepine-treated patients experienced a >50% reduction from baseline in VAS score at the end of treatment compared with placebo (35.2% vs. 18.4%, respectively; p=0.0156; number needed to treat=6.0). Global assessment of therapeutic effect rating was improved in more oxcarbazepine patients than placebo patients (48% vs. 22%, respectively; p=0.0025). Patients on oxcarbazepine were awakened less frequently due to pain than patients on placebo. Most adverse events were mild to moderate in severity, transient, and in line with the known tolerability profile of oxcarbazepine. These observations suggest that oxcarbazepine monotherapy, pending additional trials, may be efficacious and may provide clinically meaningful pain relief in patients with neuropathic pain of diabetic origin.

Adolescent↗
PubMed2006

The placebo effect in the pharmacologic treatment of patients with lower urinary tract symptoms.

OBJECTIVES: We reviewed placebo responses in randomised controlled trials (RCTs) for pharmacologic treatment of lower urinary tract symptoms (LUTS), including urinary incontinence (UI), overactive bladder, and benign prostatic hyperplasia. Review papers on placebo effects in non-urologic disorders were assessed to compare the magnitude of placebo responses in drugs for LUTS with those reported for other diseases. METHODS: Data were retrieved from registration trials for LUTS drugs on the Web sites of the Food and Drugs Administration and the European Medicines Agency. Reviews were retrieved from Medline using the MeSH term "placebo effect" (English language; published between 1990 and 2005). RESULTS: Placebo treatment of LUTS yields reductions in incontinence episodes (IEs) ranging from 32% to 65%, whereas prostate or UI symptom scores are reduced by 9-34%. Genuine drugs decrease IEs by 45-77% and symptom scores by 22-45%. Placebo responses are much lower when objective changes in voided volume or peak flow rate are assessed. CONCLUSIONS: The placebo effect in LUTS has a strong behavioural component as patients become aware of their voiding habits and potential risk factors. Symptom severity, treatment naivety, study duration, and interaction with health care providers may also influence it. Proper patient selection, study duration, and objective and subjective outcome measures may better separate genuine treatment effects from artefacts. Observational studies with patients representative for real-life situations and covering a sufficient period of time could allow for better understanding of RCT results and their applicability in clinical practice.

Adrenergic Antagonists↗
PubMed2006

Efficacy and safety of growth hormone (GH) in the treatment of adult Japanese patients with GH deficiency: a randomised, placebo-controlled study.

OBJECTIVE: The aim of this study was to assess the effect of growth hormone (GH) replacement therapy on lean body mass (LBM) and other variables including body fat mass, serum lipids and quality of life measures in GH-deficient Japanese adults. DESIGN: This was a multicentre, double-blind, placebo-controlled, parallel group study. Following initial screening, patients were randomly assigned to GH treatment (n=37) or placebo (n=36). GH treatment was started at an initial dose 0.003 mg/kg/day s.c. each day for the first 4 weeks after which the dose was increased to 0.006 mg/kg/day for 4 weeks and then to 0.012 mg/kg/day for the last 16 weeks (n=37). Body composition, serum lipids, serum IGF-I and IGFBP-3 levels were measured during the 24-week study. Short Form-36 and Quality of Life Assessment of GH Deficiency in Adults scores were also determined. RESULTS: LBM was significantly increased from baseline at 24 weeks in GH-treated patients, with a mean (+/-SD) increase of 4.7% (+/-5.3%) compared with an increase of 1.0% (+/-4.4%) in the placebo group (p<0.0001 versus baseline, p=0.0003 versus placebo). Percentage body fat decreased significantly from baseline in GH-treated patients (9.3%, p<0.0001), compared with a non-significant 0.2% increase in the placebo group (p<0.0004 for difference between treatment groups). In addition, significantly increased serum IGF-I and IGFBP-3 levels and improvements in the patients' serum lipid profiles were observed in patients who received GH therapy. Changes in quality of life measures did not differ between treatments, probably because of the small number of patients studied. GH therapy was well tolerated, with adverse events of any cause reported in 86.5% of the GH treatment group and 83.3% of the placebo group. CONCLUSION: GH treatment significantly improved body composition and serum lipid profiles in adult Japanese patients with GH deficiency compared with placebo and had no clinically relevant adverse effects.

Adult↗
PubMedDate not supplied

Inhaled zanamivir versus placebo for the prevention of influenza outbreaks in an unvaccinated long-term care population.

BACKGROUND: Antiviral chemoprophylaxis effectiveness for influenza control has not been prospectively established for unvaccinated residents of long-term care facilities. This study evaluated the efficacy and tolerability of zanamivir against the standard of care (no intervention, ie, placebo) for influenza outbreak control in a largely unvaccinated institutionalized population. OBJECTIVE: To evaluate the efficacy and tolerability of zanamivir versus placebo for influenza outbreak control in long-term care facilities. METHODS: This double-blind, randomized, placebo-controlled study prospectively enrolled/followed residents of long-term care facilities (LTCF) at 12 centers for 1 to 3 influenza seasons (1997 to 2000). Following influenza outbreak declaration, asymptomatic subjects were randomized for prophylaxis to inhaled zanamivir 10 mg or inhaled placebo given once daily for 14 days. The proportion of randomized subjects who during prophylaxis developed symptomatic, laboratory-confirmed influenza (SLCI) was the primary end point. RESULTS: Influenza outbreaks were explosive. The attack rates varied from 9.5 to 14.8 per 100 residents. Of 1763 consents given and resulting in 494 randomizations, 49% received zanamivir and 51% placebo; 66% were elderly and 9% were vaccinated. SLCI occurred in 6% of zanamivir and 9% of placebo subjects (P = .355; protective efficacy for zanamivir = 29%, 95% confidence interval 31% to 62%), and symptomatic influenza confirmed by culture in 2% and 6%, respectively (P = .052; protective efficacy = 65%, 95% confidence interval 8.5% to 86%). Zanamivir use was also associated with a 70% (95% confidence interval 13% to 89%) reduction in laboratory-confirmed influenza with fever (2% vs 6%, P = .043). Influenza B was not detected. Zanamivir was well tolerated. No virus isolate demonstrated zanamivir resistance. CONCLUSIONS: The protective efficacy of zanamivir versus placebo for SLCI was marginal, for all laboratory confirmed illnesses, but significant against culture proven and febrile influenza, suggesting zanamivir can be effective for outbreak control and symptom reduction of unvaccinated institutionalized residents. Zanamivir had an acceptable safety profile in elderly, high-risk LTCF residents and was not associated with the emergence of resistant strains.

Administration, Inhalation↗
PubMed2004

Safety and efficacy of intranasal ketamine for the treatment of breakthrough pain in patients with chronic pain: a randomized, double-blind, placebo-controlled, crossover study.

Few placebo-controlled trials have investigated the treatment of breakthrough pain (BTP) in patients with chronic pain. We evaluated the efficacy and safety of intranasal ketamine for BTP in a randomized, double-blind, placebo-controlled, crossover trial. Twenty patients with chronic pain and at least two spontaneous BTP episodes daily self-administered up to five doses of intranasal ketamine or placebo at the onset of a spontaneous BTP episode (pain intensity > or =5 on a 0-10 scale). Two BTP episodes at least 48 h apart were treated with either ketamine or placebo. Patients reported significantly lower BTP intensity following intranasal ketamine than after placebo (P < 0.0001) with pain relief within 10 min of dosing and lasting for up to 60 min. No patient in the ketamine group required his/her usual rescue medication to treat the BTP episode, while seven out of 20 (35%) patients in placebo group did (P = 0.0135). Intranasal ketamine was well tolerated with no serious adverse events. After ketamine administration, four patients reported a transient change in taste, one patient reported rhinorrhea, one patient reported nasal passage irritation, and two patients experienced transient elevation in blood pressure. A side effect questionnaire administered 60 min and 24 h after drug or placebo administration elicited no reports of auditory or visual hallucinations. These data suggest that intranasal administration of ketamine provides rapid, safe and effective relief for BTP.

Administration, Intranasal↗
PubMed2004

[Understand placebo effect to better treat pain].

PURPOSE: The clinical efficiency of every therapeutic, medicinal or other, contains a part of not specific effect, or placebo effect, of which the frequency of appearance and the importance, in the treatment of pain, can be particularly raised. The practitioners use often, deliberately either not, this effect to modulate their therapeutic efficiency, or in a diagnostic purpose to investigate the mechanism of a pain; our objective is to analyze, in the light of a review of the recent medical literature, what the understanding of the placebo effect brings to the treatment of pain. CURRENT KNOWLEDGE AND KEY POINTS: Neurobiologic mechanisms which sub-aim placebo effect begin to be understood by several studies showing the role of endogen opioid mechanisms. Other studies allow better to understand the psychological determiners of the effect placebo: conditioning mechanisms, and/or cognitive variables, as expectations of the patient or the therapist. FUTURE PROSPECTS AND PROJECTS: At term of this review, we will conclude that the use of a placebo has no value of diagnostic test as for the mechanism of the pain; it is neither necessary nor desirable to implement placebo effect in the daily practice because any therapeutics acts by associating specific and not specific effects. The quality of the relation doctor-patient will allow to mobilize not specific factors susceptible to modulate favorably any therapeutic action. For controlled clinical trials, certain methodologies can be envisaged to by-pass the administration of placebo, reducing so ethical constraints bound to their use.

Humans↗
PubMed2003

Hypertensive patients' willingness to participate in placebo-controlled trials: implications for recruitment efficiency.

BACKGROUND: Underenrollment and selective enrollment plague many clinical trials. Little is known about why hypertensive patients agree or refuse to participate in placebo-controlled trials (PCT) of antihypertensive drugs, whether the prospect of receiving placebo influences willingness to participate (WTP), or whether patients who participate differ from those who do not. METHODS: We described a hypothetical PCT of a new antihypertensive drug to 126 patients who would be eligible for ongoing phase III trials. We solicited patient motivations and concerns regarding trial participation by using open-ended questions, assessed the patients' stated WTP, and used logistic regression to determine patient characteristics associated with WTP. We reassessed WTP in 62 patients after revealing, in random order, that 10%, 30%, and 50% of patients would receive placebo. RESULTS: The most commonly cited motivations for participating included personal health benefits (40%), helping other patients (37%), and contributing to scientific knowledge (15%). The most common concerns were having to stop current medications (56%), inconvenience/annoyance (38%), fear of known side effects (35%), and the possibility of receiving placebo (24%). Overall, 47% of patients (95% confidence interval, 38% to 56%) were willing to participate. Younger patients (57% versus 37%; P =.01), nonsmokers (50% versus 24%; P =.04), and patients who had participated in research previously (77% versus 20%; P =.009) were all significantly more willing to participate. Fewer patients were willing to participate as the percentage who would receive placebo increased (P =.02), but randomly assigning fully half of patients to placebo still yielded maximal recruitment efficiency. CONCLUSIONS: Hypertensive patients participate in trials for altruistic and personal health reasons. Differences between patients who do or do not participate may influence trial outcomes. The proportion of patients receiving placebo influences some patients' enrollment decisions but is not a key determinant of recruitment efficiency.

Altruism↗
PubMed2000

Placebo-controlled trials in psychiatric research: an ethical perspective.

The placebo-controlled trial is widely regarded as the gold standard for testing the efficacy of new treatments; however, this research design is subject to ethical controversy, especially when standard treatments of proven efficacy exist. After examining regulatory standards and ethical codes relevant to placebo-controlled trials, I offer a critique of arguments against the use of placebo control groups in psychiatric research. An absolute ethical prohibition of placebo-controlled trials in psychiatric disorders for which standard, effective treatments exist is rejected because it is based on a flawed conception of research ethics, ignores important contextual factors characteristic of psychiatric research, and could lead to the approval and use of new medications that appear equivalent in efficacy to standard treatments but may be no more effective than placebos. Four standards governing the ethical use of placebos in psychiatric clinical trials are explicated: 1) placebo-controlled trials should have scientific and clinical merit; 2) risks should be minimized and justified by the anticipated benefits of generating clinically relevant scientific knowledge and the expected benefits, if any, to individual patient volunteers; 3) patient volunteers should give informed consent; and 4) investigators should offer short-term treatment optimization to patient volunteers after completion of research participation.

Antipsychotic Agents↗
PubMed2001

Placebos and paradoxes in psychiatric research: an ethics perspective.

The use of placebos in clinical trials, particularly in research with mentally ill people, has emerged as a subject of considerable controversy. We first outline ethical aspects of the primary scientific arguments for and against placebo use in research. Three examples of paradoxical aspects of the ethical use of placebos are discussed: involvement of relatively more vulnerable populations, use of apparently "less than standard" therapy, and the omission of information in placebo comparisons. In the current scientific and regulatory context, placebo use in psychiatric research may be necessary for scientific reasons, and when certain conditions are present, it may be justified on ethical grounds. Four key recommendations to facilitate the ethical use of placebos in research trials are presented. We conclude that placebo trials should be undertaken only after careful evaluation of alternative scientific strategies and, as with all human research, with great respect and genuine consideration for the individuals who choose to participate in these protocols.

Clinical Trials as Topic↗
PubMed1997

Double-blind, randomized, placebo controlled study on the effects of the monophasic oral contraceptive containing 30 micrograms ethinyl estradiol and 2.00 mg dienogest on the hemostatic system.

Forty healthy female volunteers aged between 19 and 35 years (27.3 +/- 4.1 years) with normal menstrual cycles were included in a double-blind, randomized, placebo-controlled study to investigate the influence on the hemostatic system of an oral contraceptive containing 30 micrograms ethinyl estradiol in combination with 2.00 mg dienogest, which is a 19-norprogestin without a 17 alpha-ethinyl group. At baseline and during one treatment cycle, 12 hemostatic parameters were measured on cycle days 7, 14, and 21. The hemostatic parameters were categorized as either procoagulatory, anticoagulatory and profibrinolytic, or antifibrinolytic and indicative of fibrin turnover. Differences between placebo and 30 micrograms ethinyl estradiol and 2.00 mg dienogest of plasma levels of hemostatic parameters on cycle days 21 of the precycle and treatment cycle were chosen as target variables. Prothrombin fragment 1 + 2 (F 1 + 2) was chosen as the main target variable. Equivalence of F 1 + 2 between placebo and active treatment was noted. Among the procoagulatory factors, only factor VII activity was found to be increased over placebo in the active treatment group, but decreased in the placebo group. Protein C activity increased during the treatment with 30 micrograms ethinyl estradiol and 2.00 mg dienogest, and was higher than that of the placebo group in which this parameter decreased during the treatment cycle. There was a corresponding increase in fibrinolytic activity being reflected by higher plasminogen levels in the active treatment group in comparison with placebo. An increase was noted for the fibrinolytic parameter D-dimer. Apart from isolated measurements, the parameters remained in their respective normal ranges. The data combine to suggest that 30 micrograms ethinyl estradiol and 2.00 mg dienogest has a balanced effect on the hemostatic system stimulating both procoagulatory and fibrinolytic activity.

Adult↗