SEARCH · Search PubMed

Results for “Trials”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

SourceResearch connectionFrom yearThrough year

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 631 records · Page 35Linked to original sources

PubMed2006

Surgical vs nonoperative treatment for lumbar disk herniation: the Spine Patient Outcomes Research Trial (SPORT): a randomized trial.

CONTEXT: Lumbar diskectomy is the most common surgical procedure performed for back and leg symptoms in US patients, but the efficacy of the procedure relative to nonoperative care remains controversial. OBJECTIVE: To assess the efficacy of surgery for lumbar intervertebral disk herniation. DESIGN, SETTING, AND PATIENTS: The Spine Patient Outcomes Research Trial, a randomized clinical trial enrolling patients between March 2000 and November 2004 from 13 multidisciplinary spine clinics in 11 US states. Patients were 501 surgical candidates (mean age, 42 years; 42% women) with imaging-confirmed lumbar intervertebral disk herniation and persistent signs and symptoms of radiculopathy for at least 6 weeks. INTERVENTIONS: Standard open diskectomy vs nonoperative treatment individualized to the patient. MAIN OUTCOME MEASURES: Primary outcomes were changes from baseline for the Medical Outcomes Study 36-item Short-Form Health Survey bodily pain and physical function scales and the modified Oswestry Disability Index (American Academy of Orthopaedic Surgeons MODEMS version) at 6 weeks, 3 months, 6 months, and 1 and 2 years from enrollment. Secondary outcomes included sciatica severity as measured by the Sciatica Bothersomeness Index, satisfaction with symptoms, self-reported improvement, and employment status. RESULTS: Adherence to assigned treatment was limited: 50% of patients assigned to surgery received surgery within 3 months of enrollment, while 30% of those assigned to nonoperative treatment received surgery in the same period. Intent-to-treat analyses demonstrated substantial improvements for all primary and secondary outcomes in both treatment groups. Between-group differences in improvements were consistently in favor of surgery for all periods but were small and not statistically significant for the primary outcomes. CONCLUSIONS: Patients in both the surgery and the nonoperative treatment groups improved substantially over a 2-year period. Because of the large numbers of patients who crossed over in both directions, conclusions about the superiority or equivalence of the treatments are not warranted based on the intent-to-treat analysis. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00000410.

Adult↗

PubMed2006

Effects of continuing or stopping alendronate after 5 years of treatment: the Fracture Intervention Trial Long-term Extension (FLEX): a randomized trial.

CONTEXT: The optimal duration of treatment of women with postmenopausal osteoporosis is uncertain. OBJECTIVE: To compare the effects of discontinuing alendronate treatment after 5 years vs continuing for 10 years. DESIGN AND SETTING: Randomized, double-blind trial conducted at 10 US clinical centers that participated in the Fracture Intervention Trial (FIT). PARTICIPANTS: One thousand ninety-nine postmenopausal women who had been randomized to alendronate in FIT, with a mean of 5 years of prior alendronate treatment. INTERVENTION: Randomization to alendronate, 5 mg/d (n = 329) or 10 mg/d (n = 333), or placebo (n = 437) for 5 years (1998-2003). MAIN OUTCOME MEASURES: The primary outcome measure was total hip bone mineral density (BMD); secondary measures were BMD at other sites and biochemical markers of bone remodeling. An exploratory outcome measure was fracture incidence. RESULTS: Compared with continuing alendronate, switching to placebo for 5 years resulted in declines in BMD at the total hip (-2.4%; 95% confidence interval [CI], -2.9% to -1.8%; P<.001) and spine (-3.7%; 95% CI, -4.5% to -3.0%; P<.001), but mean levels remained at or above pretreatment levels 10 years earlier. Similarly, those discontinuing alendronate had increased serum markers of bone turnover compared with continuing alendronate: 55.6% (P<.001) for C-telopeptide of type 1 collagen, 59.5% (P < .001) for serum n = propeptide of type 1 collagen, and 28.1% (P<.001) for bone-specific alkaline phosphatase, but after 5 years without therapy, bone marker levels remained somewhat below pretreatment levels 10 years earlier. After 5 years, the cumulative risk of nonvertebral fractures (RR, 1.00; 95% CI, 0.76-1.32) was not significantly different between those continuing (19%) and discontinuing (18.9%) alendronate. Among those who continued, there was a significantly lower risk of clinically recognized vertebral fractures (5.3% for placebo and 2.4% for alendronate; RR, 0.45; 95% CI, 0.24-0.85) but no significant reduction in morphometric vertebral fractures (11.3% for placebo and 9.8% for alendronate; RR, 0.86; 95% CI, 0.60-1.22). A small sample of 18 transilial bone biopsies did not show any qualitative abnormalities, with bone turnover (double labeling) seen in all specimens. CONCLUSIONS: Women who discontinued alendronate after 5 years showed a moderate decline in BMD and a gradual rise in biochemical markers but no higher fracture risk other than for clinical vertebral fractures compared with those who continued alendronate. These results suggest that for many women, discontinuation of alendronate for up to 5 years does not appear to significantly increase fracture risk. However, women at very high risk of clinical vertebral fractures may benefit by continuing beyond 5 years. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT 00398931.

Aged↗

PubMedDate not supplied

Timing the collaborative analysis of three trials comparing 5-FU plus folinic acid (FUFA) to surgery alone in the management of resected colorectal cancer: a National Cancer Institute of Canada Clinical Trials Group (NCIC-CTG) perspective.

Three cancer trials groups have decided to combine data from their separate trials examining the role of chemotherapy with 5-FU and folinic acid in the adjuvant treatment of resected colorectal carcinoma. Decisions regarding the timing of the analyses of these data have had to consider the same issues that surround early termination of ongoing trials. This paper reviews this experience from the perspective of one of the groups. It emphasizes the significant impact on decision-making of international differences of opinion concerning treatment standards.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2004

[German Database of Gene Transfer Clinical Trials. Implementation of a central registry of gene transfer clinical trials in Germany].

Continuous biotechnical development and rapid increase in knowledge in the field of research on human gene transfer raise scientific, medical, and ethical considerations in the scientific community and general public. Dissemination of new scientific findings is needed. Gene transfer studies today not only focus on monogenic diseases or life-threatening conditions such as cancer, but also comprise trials for diagnosis and prophylaxis and common medical conditions such as cardiovascular disease. This raises special attention and public discussion and requires even more the systematic monitoring and assessment of clinical trails being conducted. Whereas the number of gene transfer trials in the USA can be clearly specified, this had not been possible in Germany prior to the establishment of the DeReG database. The aim is implementation of a permanent registry comprehending all clinical gene transfer trials being conducted in Germany. Only a complete and updated database serves as a common foundation of knowledge for various groups and facilitates addressing scientific projects.

Clinical Trials as Topic↗

PubMed2006

[Non-commercial clinical trials--who will be the legal sponsor? Sponsorship of investigator-initiated clinical trials according to the German Drug Law].

Non-commercial clinical trials may be of great benefit to the patients concerned. The 12th amendment to the German Drug Law (AMG) changed legal liability of the initiators of investigator-initiated clinical trials with extensive consequences for traditional project leaders. The central point under discussion is the sponsor's responsibility according to the AMG. Presently leading management divisions of university hospitals and universities are developing proceedings to assume sponsor responsibility by institutions (institutional sponsorship), which should enable investigator-initiated clinical trials to be conducted according to legal requirements in the future. Detailed problems and special questions can only be resolved in a single-minded fashion, and if necessary political processes should be catalyzed.

Clinical Trials as Topic↗

PubMed2006

Randomized trial of tamoxifen alone or combined with fluoxymesterone as adjuvant therapy in postmenopausal women with resected estrogen receptor positive breast cancer. North Central Cancer Treatment Group Trial 89-30-52.

PURPOSE: This clinical trial evaluated the addition of fluoxymesterone (Flu) to tamoxifen (Tam) in women with resected early stage breast cancer and attempted to corroborate the findings of superiority for the combination over Tam alone seen in a previous randomized trial in metastatic disease. PATIENTS AND METHODS: Postmenopausal women with early stage breast cancer that was known to be estrogen receptor (ER) positive were randomized to treatment with Tam (20 mg per day orally for 5 years) alone or combined with Flu (10 mg orally twice per day for 1 year). The primary endpoint was relapse-free survival (RFS) defined as local-regional or distant recurrence including ductal carcinoma in situ of the ipsilateral, but not contralateral breast, and death from any cause. RESULTS: There were 541 eligible patients entered between 1991 and 1995 and the treatment arms were balanced with respect to patient characteristics. The median follow up of patients still alive was 11.4 years. No significant difference was found between Tam plus Flu and Tam alone in terms of RFS or overall survival. The adjusted hazard ratio (Tam+Flu/Tam) for relapse or death without relapse was estimated to be 0.84 (95% CI: 0.64-1.10) and that for death was 0.89 (95% CI: 0.67-1.18). As expected there was more virilization in women who received Flu. CONCLUSIONS: This clinical trial did not demonstrate superiority of Tam plus Flu over Tam alone as adjuvant therapy for postmenopausal women with resected early breast cancer known to be ER positive.

Adult↗

PubMed2005

The early glycoprotein IIb/IIIa inhibition in non-ST-segment elevation acute coronary syndrome (EARLY ACS) trial: a randomized placebo-controlled trial evaluating the clinical benefits of early front-loaded eptifibatide in the treatment of patients with non-ST-segment elevation acute coronary syndrome--study design and rationale.

BACKGROUND: The recent North American and European practice guidelines in patients with non-ST-segment elevation acute coronary syndrome (nSTE ACS) recommend glycoprotein IIb/IIIa (GpIIb-IIIa) inhibition in patients undergoing an early invasive treatment strategy. However, the guidelines are not explicit regarding the timing of initiation of GpIIb-IIIa antagonists, and there is marked variation in clinical practice regarding their use. STUDY DESIGN: The EARLY ACS trial will enroll 10,500 patients in a prospective, randomized, double blind, international, multicenter investigation of early eptifibatide compared with placebo (with provisional eptifibatide in the catheterization laboratory) in patients with high-risk nSTE ACS in whom an invasive strategy is planned no sooner than the next calendar day. The primary efficacy end point is the 96-hour composite of all-cause mortality, nonfatal myocardial infarction, recurrent ischemia requiring urgent revascularization, or need for thrombotic bailout with GpIIb-IIIa inhibitor during percutaneous coronary intervention. The key secondary end point is the composite of death or nonfatal myocardial infarction within 30 days of enrollment. IMPLICATIONS: The EARLY ACS trial will be the largest study to date to evaluate the utility of early GpIIb-IIIa inhibition in patients with nSTE ACS in whom an invasive approach is planned. This trial will provide important evidence regarding the benefit of initiating eptifibatide early after presentation with high-risk ACS versus delayed provisional use after coronary angiography. Furthermore, it will explore the ability of biomarkers to identify high-risk patients who may benefit from such an early aggressive approach.

Acute Disease↗

PubMed2006

Five years to the term breech trial: the rise and fall of a randomized controlled trial.

OBJECTIVE: On the basis of the end points of neonatal morbidity and death, the authors of the term breech trial concluded unequivocally that cesarean delivery was safer for breech babies. STUDY DESIGN: Analysis of the original and new data gives rise to serious concerns as far as study design, methods, and conclusions are concerned. In a substantial number of cases, there was a lack of adherence to the inclusion criteria. There was a large interinstitutional variation of standard of care; inadequate methods of antepartum and intrapartum fetal assessment were used, and a large proportion of women were recruited during active labor. In many instances of planned vaginal delivery, there was no attendance of a clinician with adequate expertise. RESULTS: Most cases of neonatal death and morbidity in the term breech trial cannot be attributed to the mode of delivery. Moreover, analysis of outcome after 2 years has shown no difference between vaginal and abdominal deliveries of breech babies. CONCLUSION: The original term breech trial recommendations should be withdrawn.

Breech Presentation↗

PubMed2005

The African American Heart Failure Trial: a clinical trial update.

Progressive vascular and myocardial remodeling in heart failure is effectively slowed by therapy with neurohormonal antagonists, including angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, aldosterone antagonists, and adrenergic-receptor blockers. These therapies, along with the correction of hemodynamic abnormalities, have dramatically reduced morbidity and mortality in patients with heart failure. Endothelial dysfunction, increased oxidative stress, and decreased bioavailability of nitric oxide (NO) also occur in heart failure. Data suggest that endothelial dysfunction and reduced NO bioavailability may be more prevalent in populations who self-identify as African Americans. Thus, differences observed in the African American population with respect to prevalence of heart failure, etiology, outcomes, and response to medication may in part be explained by differences in the relative contributions of neurohormonal activation and diminished NO bioavailability to the progression of heart failure. The African American Heart Failure Trial (A-HeFT) was designed to assess the benefit of fixed-dose combination isosorbide dinitrate-hydralazine (ISDN-HYD) in an African American population with advanced heart failure. The A-HeFT enrolled 1,050 African American patients with New York Heart Association (NYHA) class III-IV heart failure with dilated ventricles and low ejection fractions. Patients were randomized to receive either a fixed-dose combination of ISDN-HYD or placebo added to standard neurohormonal blockade. The primary end point was a composite score in which mortality, hospitalization, and quality of life were weighted. On July 19, 2004, the independent Data Safety Monitoring Committee recommended early termination of the trial because of a significant mortality benefit in the cohort receiving fixed-dose ISDN-HYD. The A-HeFT confirms the benefit of fixed-dose ISDN-HYD, which may enhance NO bioavailability in African American patients with NYHA class III-IV heart failure and suggests that NO-enhancing therapy is an effective new treatment strategy for heart failure. In addition, the A-HeFT affirms the critical importance of the inclusion of population subgroups in clinical trials both as a way to probe for pathophysiologic mechanisms of disease and to devise optimal treatment strategies. The rich and unique A-HeFT database will provide new opportunities to understand the pathophysiology and management of heart failure.

Adult↗

PubMed2005

Economic implications of extended-release metoprolol succinate for heart failure in the MERIT-HF trial: a US perspective of the MERIT-HF trial.

BACKGROUND: The MERIT-HF trial demonstrated improved survival and fewer hospitalizations for worsening heart failure with extended-release (ER) metoprolol succinate in patients with heart failure. This study sought to estimate the economic implications of this trial from a US perspective. METHODS AND RESULTS: A discrete event simulation was developed to examine the course of patients with heart failure. Characteristics of the population modeled, probabilities of hospitalization and death with standard therapy, and risk reductions with ER metoprolol succinate were obtained from Metoprolol CR/XL Randomized Intervention Trial in Chronic Heart Failure (MERIT-HF) and evaluated in weekly cycles. Direct medical costs were estimated from US databases in 2001 US dollars. Uncertainty in inputs was incorporated and analyses were carried out to estimate events prevented total and net costs. The model predicts that ER metoprolol succinate will prevent approximately 7 deaths and 15 hospitalizations from heart failure per 100 patients over 2 years. Compared with standard therapy alone, this translates to a cost reduction between $395 and $1112 per patient, depending on whether the costs of hospitalizations for other causes are included. Savings were maintained in 90% of the simulations. CONCLUSION: This analysis predicts that the positive effect of ER metoprolol succinate on mortality and morbidity demonstrated in MERIT-HF leads to substantial savings.

Adrenergic beta-Antagonists↗

PubMed2026

Prevention of postpartum methamphetamine use with micronized progesterone trial (PROMPT): A pilot randomized controlled trial.

OBJECTIVES: Methamphetamine use disorder (MUD) contributes to postpartum morbidity and mortality. Postpartum progesterone decline may destabilize γ-aminobutyric acid pathways, increasing craving and return to use. We assessed the feasibility and safety of micronized progesterone, generating efficacy estimates for preventing postpartum methamphetamine use. METHODS: We conducted a double-blind, randomized, placebo-controlled feasibility trial (November 2021-January 2024) at an academic center with a perinatal addiction clinic. Participants ≤ 12 weeks postpartum with ≥ 4 weeks of abstinence were randomized 1:1, stratified by opioid use disorder (OUD), to micronized progesterone 400mg (200mg twice daily) or identical placebo for 12 weeks. The primary outcome was feasibility, defined as achieving ≥ 80% of planned enrollment. Safety outcomes included adverse events (AEs) and serious adverse events (SAEs). Efficacy outcomes were return to methamphetamine use (weekly self-report and every two weeks urine toxicology) and methamphetamine craving. Analyses included intent-to-treat and per-protocol approaches, with loss to follow-up imputed as return to use. Craving trajectories were modeled using adjusted regression with interaction terms for medication for OUD (MOUD). RESULTS: Of 253 screened individuals, 43 were eligible and 34 were enrolled (91.8%; 18 progesterone, 16 placebo). Retention at 12 weeks was 88%. AE frequency was similar between groups (78% vs 81%; p > 0.05), and no maternal SAEs occurred. Four infant SAEs were deemed unrelated to treatment. Return to methamphetamine use did not differ between groups. Craving trajectories differed by MOUD type. CONCLUSIONS: Micronized progesterone was feasible and safe for postpartum individuals with MUD. MOUD-specific craving effects support evaluation in larger, multicenter efficacy trials. GOV REGISTRATION NUMBER: NCT05128071 NCT REGISTRATION: Prevention of postpartum methamphetamine use with micronized progesterone trial https://clinicaltrials.gov/study/NCT05128071.

Humans↗

PubMed2026

Foot exercise plus education versus brief advice for the treatment of plantar heel pain (FEET Trial): a feasibility randomised controlled trial.

BACKGROUND: Despite foot muscle strengthening being a target of exercise interventions for plantar heel pain (PHP) no study has measured foot muscle outcomes, and existing research is limited by a lack of control (no treatment) comparisons. OBJECTIVES: To determine the feasibility of conducting a randomised controlled trial and investigate the acceptability and credibility of comprehensive progressive foot exercise and education compared to brief advice for PHP. DESIGN: Randomised parallel group feasibility trial. METHOD: People with PHP were randomised (1:1 concealed allocation) to receive either foot exercise plus education or brief advice for twelve weeks. Primary outcomes included willingness to enrol, recruitment rate, adherence, logbook completion, dropout rate, early withdrawal reasons, adverse events, additional treatments sought, and credibility/expectancy. RESULTS: Twenty people with PHP (16 women; age 50 ± 9 years; body mass index = 30.7 ± 4.6 kg/m2) were recruited over 15 weeks (1.3 participants per week). Primary outcomes were willingness to enrol (80%), adherence (physiotherapy sessions attended: foot exercise plus education 85%, brief advice 100%; home exercise program: 62% daily sessions completed, 72% thrice weekly sessions completed), logbook completion (foot exercise plus education 75%, brief advice 90%), dropout rate (15%), and additional treatments sought (69%). There were no intervention-related adverse events, and credibility scores were higher for foot exercise plus education. CONCLUSIONS: This study confirms feasibility and acceptability of a protocol comparing foot exercise plus education with brief advice in individuals with PHP, generating key insights to inform future trial design.

Humans↗

PubMed1997

Clinical studies on beta blockers and heart failure preceding the MERIT-HF Trial. Metoprolol CR/XL Randomized Intervention Trial in Heart Failure.

With greater understanding of the impact of neuroendocrine stimulation on the adverse outcomes of heart failure, especially lethal arrhythmias and sudden cardiac death, focus has returned to the potential benefits of beta-adrenergic blockade. In patients with myocardial infarction and left ventricular (LV) dysfunction, particularly those prone to life-threatening arrhythmias, beta-blocker therapy has been associated with a lower incidence of arrhythmias and improved survival. Even in the absence of angiotensin-converting enzyme (ACE) inhibition, beta blockade has improved cardiac function and LV contractility in nonischemic heart failure, leading to a decrease in LV end-diastolic pressure and improved clinical status. Both the Metoprolol in Dilated Cardiomyopathy (MDC) trial and the Cardiac Insufficiency Bisoprolol Study (CIBIS) found beta blockade to be associated with decreased mortality rates in patients with nonischemic heart failure. Of the 3 large randomized mortality trials now under way, the Metoprolol CR/XL Randomized Intervention Trial in Heart Failure (MERIT-HF) is specifically designed to investigate the effects of beta blockade on total mortality when used as an adjunct to ACE inhibition in patients with ischemic or nonischemic heart failure. Unresolved issues to be addressed include whether: (1) beta-blocker therapy in heart failure can improve survival and/or reduce the incidence of sudden cardiac death; (2) beta blockade is equally effective in ischemic and nonischemic heart failure; (3) any specific beta blocker may be better tolerated initially and cause fewer adverse effects; and (4) all beta blockers result in improved exercise tolerance and quality of life.

Adrenergic beta-Antagonists↗

PubMedDate not supplied

External validity of randomised controlled trials: "to whom do the results of this trial apply?".

In making treatment decisions, doctors and patients must take into account relevant randomised controlled trials (RCTs) and systematic reviews. Relevance depends on external validity (or generalisability)--ie, whether the results can be reasonably applied to a definable group of patients in a particular clinical setting in routine practice. There is concern among clinicians that external validity is often poor, particularly for some pharmaceutical industry trials, a perception that has led to underuse of treatments that are effective. Yet researchers, funding agencies, ethics committees, the pharmaceutical industry, medical journals, and governmental regulators alike all neglect external validity, leaving clinicians to make judgments. However, reporting of the determinants of external validity in trial publications and systematic reviews is usually inadequate. This review discusses those determinants, presents a checklist for clinicians, and makes recommendations for greater consideration of external validity in the design and reporting of RCTs.

Data Interpretation, Statistical↗

PubMed2002

Up-front centralized data review and individualized treatment proposals in a multicenter pediatric Hodgkin's disease trial with 71 participating hospitals: the experience of the German-Austrian pediatric multicenter trial DAL-HD-90.

BACKGROUND AND PURPOSE: A systematic procedure for up-front centralized data review and the set-up of individualized treatment proposals was integrated prospectively into the German-Austrian multicenter trial DAL-HD-90 for pediatric Hodgkin's disease (HD) in order to introduce local radiotherapy according to the individual patient's spread of disease within a combined-modality treatment. This paper investigates the feasibility of such a procedure and its impact on the final definition of the extent and stage of disease as well as on the choice of treatment. PATIENTS AND METHODS: Between October 1990 and July 1995, 578 children and adolescents <18 years (259 girls, 319 boys, median age 12.9 years) with HD were enrolled into the HD-90 trial. After clinical and pathological staging (66.4/33.6%), patients were allocated to treatment groups (TG) 1 'early stage', TG2 'intermediate stage', or TG3 'advanced stage'. All groups underwent two cycles of OPPA (vincristine, prednisone, procarbazine, doxorubicin) (girls) or OEPA (E, etoposide) (boys) for induction chemotherapy. TG2 and TG3 continued on as two or four cycles, respectively, of COPP (C, cyclophosphamide). Low-dose local radiotherapy was given to the initially involved sites, with radiation doses of 25 Gy in TG1/TG2, and 20 Gy in TG3. All documentation forms, radiographs, and chest and abdominal computed tomography (CT) scans were centrally reviewed, addressing in particular the individual patient's extent and stage of disease. This review and the set-up of individualized treatment proposals were in the hands of the study coordinator, one additional pediatrician and two radiation oncologists and radiologists at the study center. During a time slot of at least 8 weeks (two cycles of standard chemotherapy in all three TGs) the individualized treatment proposals were to be sent to the participating hospital. RESULTS: Complete sets of documentation from 564/578 patients (97.6%) were submitted sufficiently early to the study center. A total of 285 out of 574 chest radiographs, 468 out of 553 chest CT scans and 421 out of 548 abdominal CT scans were available from 71 hospitals. A total of 564 individualized treatment proposals were worked out by the review group and sent to the hospitals before radiotherapy began. Re-analysis of images and documentation forms, including laboratory and clinical data, resulted in a revision of stage in 115/571 patients (20.1%) and of TG in 76/571 patients (13.3%). A total of 67/76 patients were shifted into a higher TG, 60 patients on account of additionally detected extralymphatic involvement, five patients because of additionally detected lymph node involvement and two patients due to clinical data which had to be classified as B-symptoms. A total of 9/76 patients were shifted into a lower TG; in three patients extranodal disease and in six patents local lymph node involvement could not be confirmed. CONCLUSIONS: The up-front centralized review of patient data and consecutive set-up and delivery of individualized treatment proposals for almost every patient are feasible within a large multicenter trial. Sufficient time and manpower at the study center are needed for the review process and the set-up of individualized treatment proposals. Such a procedure has a significant impact on the homogeneity of stage definition, allocation to TG, and individualized treatment proposals.

Adolescent↗

PubMed2001

Trials within trials: confirmatory subgroup analyses in controlled clinical experiments.

Subgroup analyses remain a popular and necessary component of controlled clinical trials. However, lack of prospective specification, inadequate sample size, inability to maintain power, and the cumulative effect of sampling error can complicate their interpretation. This article demonstrates that clinical trial design tools that would allow the medical community to draw confirmatory and not just exploratory conclusions from specific subgroup evaluations are available to methodologists. Distinct from the use of a treatment by subgroup interaction term, this methodology provides an evaluation of the effect of an intervention within a particular subgroup stratum prospectively declared to be of interest to the investigators. The necessary prespecification of stratum-specific type I error rates, when combined with (1) a stratum-specific event rate in the subgroup, (2) a stratum-specific primary endpoint, (3) a stratum-specific endpoint precision, and/or (4) a stratum-specific efficacy, satisfies the requirements for a subgroup stratum's "stand-alone" interpretation at the trial's conclusion.

Clinical Trials as Topic↗

PubMed1993

Economic evaluation and quality of life assessments in cancer clinical trials: the CHART Trial.

Arguments are being made more frequently to incorporate economic evaluations and quality of life assessments into clinical trials. Using a randomised, multicentre, phase 3 cancer clinical trial as an example, this paper outlines the importance of including such assessments; the practical considerations associated with the design of such trials; the methods for collecting such data; and, how such data can be used. Finally, it is emphasised that the anticipated benefits of collecting data relating to resource use and quality of life should outweigh the associated costs to research funding organisations.

Clinical Trials, Phase III as Topic↗

PubMed1999

Rationale for randomised trials of prostate cancer screening. The International Prostate Screening Trial Evaluation Group.

Screening for prostate cancer has been advocated by a number of organisations largely because there is good evidence that administration of the test for prostate specific antigen (PSA) results in the detection of cancers at an early stage. However, the mere fact that a cancer can be detected earlier in its natural history by screening is no guarantee that benefit will follow. Further, screening for prostate cancer can substantially impair the quality of life of those with detected and treated cancer, that would not otherwise have reduced life expectancy. The only established mechanism to evaluate the efficacy of screening is the randomised controlled trial. In this paper we review the trials contributing to our collaboration, the advantages that will flow from them, and the reasons why decisions on the introduction of population-based screening for prostate cancer cannot be made before these trials have come to fruition.

Aged↗