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Trial Design (trial + design)
Kinds of Trial Design Selected AbstractsNovel Clinical Trial Designs for Treatment of Ductal Carcinoma In Situ of the Breast with Trastuzumab (Herceptin)THE BREAST JOURNAL, Issue 1 2007Ricardo J. Gonzalez MD Abstract:, Because ductal carcinoma in situ (DCIS) avidly expresses Her2/neu, the target of the monoclonal antibody trastuzumab, and because trastuzumab has been shown to be effective against invasive breast cancer, trastuzumab may be effective for reducing the tumor burden and abrogating or reversing the hypothesized transition from in situ to invasive disease in patients with DCIS. To test this hypothesis, a trial of neoadjuvant trastuzumab for DCIS has been opened at our institution. Because trastuzumab has been shown to act as a radiosensitizing agent for Her2/neu-overexpressing cancer and because there are currently no systemic treatments for estrogen-receptor-negative DCIS, it makes sense to investigate whether use of trastuzumab concurrently with postoperative radiation therapy improves local control of DCIS. The National Surgical Adjuvant Breast and Bowel Project (NSABP) is planning a trial to test this hypothesis. The risk of cardiac toxicity associated with the doses of trastuzumab planned for these trials (cumulative doses of 8 mg/kg for our trial and 14 mg/kg in the NSABP trial) is believed to be minimal, but the safety profile of these approaches will need to be closely monitored. [source] Mania associated with antidepressant treatment: comprehensive meta-analytic reviewACTA PSYCHIATRICA SCANDINAVICA, Issue 6 2010L. Tondo Tondo L, Vázquez G, Baldessarini RJ. Mania associated with antidepressant treatment: comprehensive meta-analytic review. Objective:, To review available data pertaining to risk of mania,hypomania among bipolar (BPD) and major depressive disorder (MDD) patients with vs. without exposure to antidepressant drugs (ADs) and consider effects of mood stabilizers. Method:, Computerized searching yielded 73 reports (109 trials, 114 521 adult patients); 35 were suitable for random effects meta-analysis, and multivariate-regression modeling included all available trials to test for effects of trial design, AD type, and mood-stabilizer use. Results:, The overall risk of mania with/without ADs averaged 12.5%/7.5%. The AD-associated mania was more frequent in BPD than MDD patients, but increased more in MDD cases. Tricyclic antidepressants were riskier than serotonin-reuptake inhibitors (SRIs); data for other types of ADs were inconclusive. Mood stabilizers had minor effects probably confounded by their preferential use in mania-prone patients. Conclusion:, Use of ADs in adults with BPD or MDD was highly prevalent and moderately increased the risk of mania overall, with little protection by mood stabilizers. [source] Patient-centred and professional-directed implementation strategies for diabetes guidelines: a cluster-randomized trial-based cost-effectiveness analysisDIABETIC MEDICINE, Issue 2 2006R. F. Dijkstra Abstract Aims Economic evaluations of diabetes interventions do not usually include analyses on effects and cost of implementation strategies. This leads to optimistic cost-effectiveness estimates. This study reports empirical findings on the cost-effectiveness of two implementation strategies compared with usual hospital outpatient care. It includes both patient-related and intervention-related cost. Patients and methods In a clustered-randomized controlled trial design, 13 Dutch general hospitals were randomly assigned to a control group, a professional-directed or a patient-centred implementation programme. Professionals received feedback on baseline data, education and reminders. Patients in the patient-centred group received education and diabetes passports. A validated probabilistic Dutch diabetes model and the UKPDS risk engine are used to compute lifetime disease outcomes and cost in the three groups, including uncertainties. Results Glycated haemoglobin (HbA1c) at 1 year (the measure used to predict diabetes outcome changes over a lifetime) decreased by 0.2% in the professional-change group and by 0.3% in the patient-centred group, while it increased by 0.2% in the control group. Costs of primary implementation were < 5 Euro per head in both groups, but average lifetime costs of improved care and longer life expectancy rose by 9389 Euro and 9620 Euro, respectively. Life expectancy improved by 0.34 and 0.63 years, and quality-adjusted life years (QALY) by 0.29 and 0.59. Accordingly, the incremental cost per QALY was 32 218 Euro for professional-change care and 16 353 for patient-centred care compared with control, and 881 Euro for patient-centred vs. professional-change care. Uncertainties are presented in acceptability curves: above 65 Euro per annum the patient-directed strategy is most likely the optimum choice. Conclusion Both guideline implementation strategies in secondary care are cost-effective compared with current care, by Dutch standards, for these patients. Additional annual costs per patient using patient passports are low. This analysis supports patient involvement in diabetes in the Netherlands, and probably also in other Western European settings. [source] Diabetes control and complications: the role of glycated haemoglobin, 25 years onDIABETIC MEDICINE, Issue 7 2004S. L. Jeffcoate Abstract The long-term complications of diabetes have major consequences for individual subjects and growing healthcare delivery and cost implications for society. Evidence for the benefits of good glycaemic control, as monitored by glycated haemoglobin measurements, has been developed in the 25 years since they were introduced to the point where HbA1c assays play central roles in patient management, clinical guidance and audit, and clinical trial design. In this review this evidence is examined and three classes of uncertainty identified that diminish confidence in the effectiveness of these roles for HbA1c. 1Analytical variability between different methods for HbA1c has restricted the application of clinical targets and this problem has recently been addressed by reference method standardization. There are two approaches to this which result in different HbA1c values and this discrepancy needs to be resolved. 2Biological variability in HbA1c values between individuals also restricts its predictive role when applied to populations. The correlations between HbA1c measurements and various components of glycaemia (overall, fasting, postprandial) are still uncertain and differences in protein glycation and de-glycation are greater between subjects than often thought. The influence of variability in erythrocyte life span is an area where research is needed, especially in diabetic subjects. 3Clinical variability is the most important and complex area of uncertainty. A predictive link between HbA1c and clinical outcomes is not as clear-cut as often stated. The correlation with the development of microvascular disease is well established in Type 1 diabetes, but in Type 2 subjects (90% of those with diabetes) the evidence that HbA1c monitoring is of value in predicting or preventing macrovascular disease is not strong, although it is the major cause of morbidity and early death in this group. It is recommended that, as a matter of urgency, these issues be examined, particularly within the context of self-care in diabetes. Diabet. Med. **, ***,*** (2003) [source] Clinical trial design in status epilepticus: problems and solutionsEPILEPSIA, Issue 2007Brian G. R. Neville No abstract is available for this article. [source] Cocaine Rapid Efficacy Screening Trial (CREST): a paradigm for the controlled evaluation of candidate medications for cocaine dependenceADDICTION, Issue 2005Deborah B. Leiderman ABSTRACT Aim Development of effective medications for the treatment of cocaine dependence remains a major priority for the National Institute on Drug Abuse (NIDA) at the National Institutes of Health. The Cocaine Rapid Efficacy Screening Trial (CREST) paradigm was developed by the Division of Treatment Research and Development (DT R&D) at NIDA with the goal of enhancing pilot clinical trial validity when systematically assessing a range of medications and drug classes for potential utility in treatment of cocaine dependence. Design CREST utilizes a randomized, controlled, parallel group, blinded methodology for comparing one or more marketed medications against a standard, pharmaceutical grade placebo. The trial design is comprised of a flexible 2,4-week screening/baseline period followed by randomization to an 8-week treatment period. Measures Standard measures of outcomes for the CREST included urinary benzoylecgonine (primary metabolite of cocaine), retention, cocaine craving, depression, clinical global impression and HIV-risk behaviors. In order to facilitate comparisons of data from the CREST studies across sites, drug classes and time, standardized procedures, measures and psychosocial counseling were used. Results A total of 19 medications were evaluated in out-patient treatment research clinics in Boston, Cincinnati, Los Angeles, New York and Philadelphia. Conclusions Findings supported decisions to move forward three medications (cabergoline, reserpine, tiagabine) using full-scale, adequately powered, randomized placebo-controlled trial designs. Lessons learned from the CREST experience continue to shape cocaine pharmacotherapy trial design and execution. [source] Optimal clinical trial design using value of information methods with imperfect implementationHEALTH ECONOMICS, Issue 5 2010Andrew R. Willan Abstract Traditional sample size calculations for randomized clinical trials are based on the tests of hypotheses and depend on somewhat arbitrarily chosen factors, such as type I and II errors rates and the smallest clinically important difference. In response to this, many authors have proposed the use of methods based on the value of information as an alternative. Previous attempts have assumed perfect implementation, i.e. if current evidence favors the new intervention and no new information is sought or expected, all future patients will receive it. A framework is proposed to allow for this assumption to be relaxed. The profound effect that this can have on the optimal sample size and expected net gain is illustrated on two recent examples. In addition, a model for assessing the value of implementation strategies is proposed and illustrated. Copyright © 2009 John Wiley & Sons, Ltd. [source] Patient and clinician collaboration in the design of a national randomized breast cancer trialHEALTH EXPECTATIONS, Issue 1 2004Jo Marsden MD FRCS (Gen Surgery) Abstract Objective, To show breast cancer patient involvement in the design of a national randomized trial of hormone replacement therapy (HRT) in symptomatic patients will increase accrual. Setting and participants, Three stakeholder groups [(1) researchers from the Lynda Jackson Macmillan Centre, (2) the Consumers' Advisory Group for Clinical Trials (CAG-CT), (3) clinicians responsible for a pilot randomized HRT study in breast cancer patients] developed this collaborative study. Methods, (1) Nine focus group discussions were conducted to identify issues relevant to breast cancer patients about HRT and a national trial: six involved women from breast cancer support groups nationwide and three patients who had previously participated in the pilot randomized HRT study. (2) Recommendations from the focus groups (analysed by Grounded Theory) were debated by the research stakeholders and focus group representatives at a 1-day meeting and consensus reached (using a voting system) on mutual priorities for incorporation into the design of a national HRT trial. (3) Representatives from the CAG-CT and focus groups participated in subsequent national HRT steering committee meetings to ensure that these priorities were accounted for and the resulting trial design summary was circulated to the CAG-CT and all focus group representatives for comment. Results, Focus groups demonstrated that the complexity of factors relating to trial participation was not just restricted to the research topic in question. Patient,clinician interaction provided a platform for negotiating potential conflicts over trial design and outcomes. Patient feedback suggested that mutually agreed priorities were accounted for in the trial design. Interpretation, Clinical research planning should involve all research stakeholders at the outset. Quantifying the impact of patient involvement in terms of trial accrual may be too simple given the complexity of their motivations for participating in trials. [source] Mirtazapine naturalistic depression study (in Sweden),MINDS(S): clinical efficacy and safetyHUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 3 2006Jan Wålinder Abstract Objective To study how implementation of a naturalistic trial design for mirtazapine treatment in major depressive disorder for six (up to 12) months could be used and evaluated by means of clinical efficacy and safety. Method An open-labelled, prospective, multicenter, non-comparative trial was conducted during a 2-year period in patients with major depression according to DSM-IV treated in psychiatric departments and primary care in Sweden. Minimal inclusion and exclusion criteria were used in order to diminish the potential patient selection bias. Maximum flexibility of the dosage of mirtazapine was allowed, and clinical assessments included MADRS, CGI, vital signs and spontaneous reporting of adverse events. Results 192 patients were found eligible and enrolled in the study. A significant improvement in depressive symptoms according to MADRS and CGI was observed including particularly marked sleep improvement early in the treatment. Slight increases in body weight and BMI were observed. The investigational drug was well tolerated overall. Conclusion The clinical efficacy and safety of mirtazapine found in this naturalistic setting is in line with previously reported data on mirtazapine in traditional controlled clinical trials. The results confirm that the naturalistic study design facilitated conduct of the trial. The authors suggest that this type of study design should also be applied to other antidepressant drugs that are frequently prescribed in the general population. Copyright © 2006 John Wiley & Sons, Ltd. [source] Phenotype classification in IBD: Is there an impact on therapy?INFLAMMATORY BOWEL DISEASES, Issue 12 2007Aaron Walfish MD Abstract This review summarizes the current phenotypic classifications of inflammatory bowel disease (IBD) and outlines their implications for diagnosis, therapy, prognosis, clinical trial design, and genotype-phenotype correlations. (Inflamm Bowel Dis 2007) [source] Cutting through the statistical fog: understanding and evaluating non-inferiority trialsINTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 10 2010W. S. Weintraub Summary Every year, results from many important randomised, controlled trials are published. Knowing the elements of trial design and having the skills to critically read and incorporate results are important to medical practitioners. The goal of this article is to help physicians determine the validity of trial conclusions to improve patient care through more informed medical decision making. This article includes a review of 162 randomised, controlled non-inferiority (n = 116) and equivalence (n = 46) hypothesis studies as well as the larger Stroke Prevention using Oral Thrombin Inhibitor in atrial Fibrillation V study and the Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial. Evaluation of data from small and large trials uncovers significant flaws in design and models employed and uncertainty about calculations of statistical measures. As one example of questionable study design, discussion includes a large (n = 3922), double-blind, randomised, multicentre trial comparing the efficacy of ximelagatran with warfarin for prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation and additional stroke risk factors. Investigators concluded that ximelagatran was effective compared with well-controlled warfarin for prevention of thromboembolism. However, deficiencies in design, as well as concerns about liver toxicity, resulted in the rejection of the drug by the US Food and Drug Administration. Many trials fail to follow good design principles, resulting in conclusions of questionable validity. Well-designed non-inferiority trials can provide valuable data and demonstrate efficacy for beneficial new therapies. Objectives and primary end-points must be clearly stated and rigorous standards met for sample size, establishing the margin, patient characteristics and adherence to protocol. [source] The Virtual International Stroke Trials Archive (VISTA): results and impact on future stroke trials and management of stroke patientsINTERNATIONAL JOURNAL OF STROKE, Issue 2 2010C. Weimar Background The Virtual International Stroke Trials Archive was established to improve stroke care and trial design through the collation, categorization and potential access to data sets from clinical trials for the treatment of stroke. Methods Virtual International Stroke Trials Archive currently provides access to a combined data set of 29 anonymised acute stroke trials and one acute stroke registry with data on >27 500 patients aged between 18 and 103 (mean 71) years. Results Virtual International Stroke Trials Archive has facilitated research across a broad canvas. The prognosis was poor in patients with very high blood pressure at the time of admission or with a wide variability of systolic blood pressure during the acute phase. The late occurrence of hyperthermia following an ischaemic stroke worsens the prognosis. Stroke lateralisation is not an important predictor of cardiac adverse events or 90-day mortality. Haemorrhagic transformation is seen frequently in patients with cardio-embolic strokes and is associated with a poor prognosis when occurring after the acute phase. Virtual International Stroke Trials Archive has allowed various prognostic models for patients with ischaemic or haemorrhagic stroke to be established and validated. More direct outcomes such as lesion volume can be useful in phase II clinical trials for determining whether a phase III trial should be undertaken. New outcome measures such as ,home time' may also strengthen future trials. On a worldwide level, the prognosis of stroke patients differs considerably between various countries. Conclusion Virtual International Stroke Trials Archive provides an excellent opportunity for analysis of natural history data and prognosis. It has the potential to influence clinical trial design and implementation through exploratory data analyses. [source] The STRokE DOC trial technique: ,video clip, drip, and/or ship'INTERNATIONAL JOURNAL OF STROKE, Issue 4 2007B. C. Meyer Rationale To describe the clinical trial methods of a site-independent telemedicine system used in stroke. Aims A lack of readily available stroke expertise may partly explain the low rate of rt-PA use in acute stroke. Although telemedicine systems can reliably augment expertise available to rural settings, and may increase rt-PA use, point-to-point systems do require fixed base stations. Site-independent systems may minimize delay. The STRokE DOC trial assesses whether site-independent telemedicine effectively and efficiently brings rt-PA to a remote population. Design STRokE DOC is a 5-year, 400-participant, noninvasive trial, comparing two consultative techniques at four remote sites. Participants are randomized to acute ,STRokE DOC telemedicine' or ,telephone' consultations. Treatment decision accuracy is adjudicated at two time points, using three levels of data availability and an independent auditor. Study outcomes The primary outcome measure is whether there was a ,correct decision to treat or not to treat using rt-PA' at each of three adjudication levels (primarily at Level #2). Secondary outcomes include the number of thrombolytic recommendations, intracerebral hemorrhage, and 90-day outcomes. Using the STRokE DOC system (or telephone evaluation), medical history, neurologic scales, CT interpretations, and recommendations have been completed on over 200 participants to date. Of the initial 11, nonrandomized, ,run-in' patients, six (65%) were evaluated wirelessly, and five (45%) were evaluated with a site-independent LAN or cable modem. Three (27%) received rt-PA. The adjudication methodology was able to show both agreements and disagreements in these 11 cases. It is feasible to perform site-independent stroke consultations, and adjudicate those cases, using the STRokE DOC system and trial design. Telemedicine efficacy remains to be proven. [source] Review of nursing care for patients undergoing percutaneous coronary intervention: a patient journey approachJOURNAL OF CLINICAL NURSING, Issue 17 2009John X Rolley Aim., To evaluate the existing literature to inform nursing management of people undergoing percutaneous coronary intervention. Background., Percutaneous coronary intervention is an increasingly important revascularisation strategy in coronary heart disease management and can be an emergent, planned or rescue procedure. Nurses play a critical role in delivering care in both the independent and collaborative contexts of percutaneous coronary intervention management. Design., Systematic review. Method., The method of an integrative literature review, using the conceptual framework of the patient journey, was used to describe existing evidence and to determine important areas for future research. The electronic data bases CINAHL, Medline, Cochrane and the Joanna Briggs data bases were searched using terms including: (angioplasty, transulminal, percutaneous coronary), nursing care, postprocedure complications (haemorrhage, ecchymosis, haematoma), rehabilitation, emergency medical services (transportation of patients, triage). Results., Despite the frequency of the procedure, there are limited data to inform nursing care for people undergoing percutaneous coronary intervention. Currently, there are no widely accessible nursing practice guidelines focusing on the nursing management in percutaneous coronary intervention. Findings of the review were summarised under the headings: Symptom recognition; Treatment decision; Peri-percutaneous coronary intervention care, describing the acute management and Postpercutaneous coronary intervention management identifying the discharge planning and secondary prevention phase. Conclusions., Cardiovascular nurses need to engage in developing evidence to support guideline development. Developing consensus on nurse sensitive patient outcome indicators may enable benchmarking strategies and inform clinical trial design. Relevance to clinical practice., To improve the care given to individuals undergoing percutaneous coronary intervention, it is important to base practice on high-level evidence. Where this is lacking, clinicians need to arrive at a consensus as to appropriate standards of practice while also engaging in developing evidence. This must be considered, however, from the central perspective of the patient and their family. [source] A systematic review of the efficacy of non-pharmacological treatments for depression on glycaemic control in type 2 diabeticsJOURNAL OF CLINICAL NURSING, Issue 19 2008Mei-Yeh Wang Aims and objectives., This paper reported a systematic review of three randomised controlled clinical trials evaluating the efficacy of non-pharmacological treatment of depression on glycaemic control in individuals with type 2 diabetes. Background., Depression is associated with poor adherence to self-care regimen in individuals with diabetes. A significant relationship between depression and poor glycaemic control has also been suggested. Hence, the management of depression becomes an important aspect of diabetes care. Design., Systematic review. Methods., Cochrane library, Pubmed, MEDLINE, EBM review, ProQuest Medical Bundle and SCOPUS databases were searched using the following medical subject headings or key words , depression, mood disorder, depressive symptoms, diabetes mellitus, glycaemic control, glycated haemoglobin, glucose, psychological therapy, psychotherapy, non-pharmacological therapy and cognitive behaviour therapy. The publication date was limited from 1996,2007. Studies were selected if they used a randomised controlled trial design, were written in English, used non-pharmacological treatments for treating depression, included individuals with type 2 diabetes mellitus as participants and included depressive symptoms and glycaemic control (determined by haemoglobin A1C) as outcomes. Results., Non-pharmacological treatments of depression reduce depressive symptoms in diabetic patients. However, cognitive behaviour therapy did not improve glycaemic control. The treatment effect sizes for glycaemic control in the two collaborative-care programmes were also small. Conclusions., The available evidence indicated that non-pharmacological treatment of depression had limited effect on glycaemic control in individuals with type 2 diabetes. Relevance to clinical practice., The depression-focused interventions might not achieve optimal diabetes-related outcomes. The beneficial effect of psychological treatment for glycaemic control may be strengthened by employing treatments tailored to each individual's diabetes self-care needs in addition to depression management. [source] A systematic review of nursing contributions to mobility rehabilitation: examining the quality and content of the evidenceJOURNAL OF CLINICAL NURSING, Issue 11c 2007Rosie Kneafsey BSc Aims., This paper summarizes the results of a systematic literature review to examine the quality and content of the evidence relating to nursing approaches to improving the mobility and movement of older people. Background., Older people experiencing health breakdown often develop problems with movement and mobility and nurses play a role in helping patients to either adapt to or overcome these difficulties. Methods., Electronic searches were undertaken of Medline, CINAHL, Amed and Cochrane Database of systematic reviews. Papers about nursing approaches to promoting mobility and movement were critically appraised using quality assessment checklists. Papers addressing safe moving and handling, falls prevention, health promotion, rehabilitation or teamworking in general were excluded. Results., Sixteen research and 33 informational papers were included and comprise the review. Many research papers used weak designs and small sample sizes, limiting their ability to control for important confounding variables. Although numerous studies examined effectiveness, only one used a randomised controlled trial design. Papers were grouped into four interlinked sets. These were promoting mobility and preventing immobility; walking and exercise; neuro-developmental principles; and rehabilitation patient handling. Conclusions., Specific foci for nursing assessment and interventions to promote patients' mobility have been identified. However, the fragmented nature of the evidence makes it difficult to make recommendations for nursing practice. Future research should be conducted by multi-professional research teams to identify the most effective approaches to promoting patients' mobility and to explore overlaps between different members of the rehabilitation team. Relevance to clinical practice., Regaining the ability to move and walk is often a key concern for patients who have suffered health breakdown. Although nurses provide patients with assistance the evidence available does little to direct nurses as to the best approach towards mobility rehabilitation. It is important that nurses play a role in measuring the efficacy of different interventions to promote rehabilitation. [source] Analytical epidemiology of periodontitisJOURNAL OF CLINICAL PERIODONTOLOGY, Issue 2005Luisa N. Borrell Abstract Aims: To review the literature related to the analytical epidemiology of periodontitis generated over the past decade. This review does not deal with descriptive epidemiologic studies of the prevalence, extent and severity of periodontitis with respect to global geography, but focuses exclusively on analytical epidemiology issues, including the challenges posed by the use of different case definitions across studies, current theories and models of disease progression, and risk factors associated with the onset and progression of periodontitis. Methods: Relevant publications in the English language were identified after Medline and PubMed database searches. Findings and conclusions: There is a conspicuous lack of uniformity in the definition of periodontitis used in epidemiologic studies, and findings from different research groups are not readily interpretable. There is a lack of studies that specifically address the distinction between factors responsible for the onset of periodontitis versus those affecting its progression. Colonization by specific bacteria at high levels, smoking, and poorly controlled diabetes have been established as risk factors for periodontitis, while a number of putative factors, including specific gene polymorphisms, have been identified in association studies. There is a clear need for longitudinal prospective studies that address hypotheses emerging from the cross-sectional data and include established risk factors as covariates along with new exposures of interest. Intervention studies, fulfilling the "targeting" step of the risk assessment process, are particularly warranted. Obvious candidates in this context are studies of the efficacy of elimination of specific bacterial species and of smoking cessation interventions as an alternative to the traditional broad anti-plaque approach in the prevention and control of periodontitis. Ideally, such studies should have a randomized-controlled trial design. [source] Conducting suicide research in naturalistic clinical settings,JOURNAL OF CLINICAL PSYCHOLOGY, Issue 4 2009David A. Jobes Abstract Unique challenges arise for clinical researchers designing studies focused on suicidal behaviors due to the inherently high-risk nature of such research. Traditional approaches to clinical trial design are briefly discussed, highlighting the limitations and obstacles of these approaches when working with suicidal individuals. Using their own personal experiences and setbacks from an ongoing clinical suicidology research program, the authors argue for greater emphasis on effectiveness and translational research designs conducted in naturalistic clinical settings to test the practical utility of empirically-supported treatments for suicidal behaviors, to gain new perspectives on suicidal individuals, and to better understand the nature of suicidal risk. © 2009 Wiley Periodicals, Inc. J Clin Psychol 65:1,14, 2009. [source] Prospective Registration of Clinical Trials in India: Strategies, Achievements & ChallengesJOURNAL OF EVIDENCE BASED MEDICINE, Issue 1 2009Prathap Tharyan Abstract Objective This paper traces the development of the Clinical Trial Registry-India (CTRI) against the backdrop of the inequities in healthcare and the limitations in the design, conduct, regulation, oversight and reporting of clinical trials in India. It describes the scope and goals of the CTRI, the data elements it seeks and the process of registering clinical trials. It reports progress in trial registration in India and discusses the challenges in ensuring that healthcare decisions are informed by all the evidence. Methods A descriptive survey of developments in clinical trial registration in India from publications in the Indian medical literature supplemented by firsthand knowledge of these developments and an evaluation of how well clinical trials registered in the CTRI up to 10 January, 2009 comply with the requirements of the CTRI and the World Health Organization's International Clinical Trial Registry (WHO ICTRP). Results Considerable inequities exist within the Indian health system. Deficiencies in healthcare provision and uneven regulation of, and access to, affordable healthcare co-exists with a large private health system of uneven quality. India is now a preferred destination for outsourced clinical trials but is plagued by poor ethical oversight of the many trial sites and scant information of their existence. The CTRI's vision of conforming to international requirements for transparency and accountability but also using trial registration as a means of improving trial design, conduct and reporting led to the selection of registry-specific dataset items in addition to those endorsed by the WHO ICTRP. Compliance with these requirements is good for the trials currently registered but these trials represent only a fraction of the trials in progress in India. Conclusion Prospective trial registration is a reality in India. The challenges facing the CTRI include better engagement with key stakeholders to ensure increased prospective registration of clinical trials and utilization of existing legislative opportunities to complement these efforts. [source] Community-based programmes to prevent falls in children: A systematic reviewJOURNAL OF PAEDIATRICS AND CHILD HEALTH, Issue 9-10 2005Rod McClure Objective: We systematically reviewed the literature to examine the evidence for the effectiveness of community-based interventions to reduce fall-related injury in children aged 0,16 years. Methods: We performed a comprehensive search of the literature using the following study selection criteria: community-based intervention study; target population was children aged 0,16 years; outcome measure was fall-related injury rates; and either a community control or historical control was used in the study design. Quality assessment and data abstraction were guided by a standardized procedure and performed independently by two authors. Results: Only six studies fitting the inclusion criteria were identified in our search and only two of these used a trial design with a contemporary community control. Neither of the high quality evaluation studies showed an effect from the intervention and while authors of the remaining studies reported effective falls prevention programmes, the pre- and post-intervention design, uncontrolled for background secular trends, makes causal inferences from these studies difficult. Conclusion: There is a paucity of research studies from which evidence regarding the effectiveness of community-based intervention programmes for the prevention of fall-related injury in children could be based. [source] Design and Implementation of a Multicenter Trial of Vitamin E in Aging Individuals with Down SyndromeJOURNAL OF POLICY AND PRACTICE IN INTELLECTUAL DISABILITIES, Issue 2 2005Paul S. Aisen Abstract, Older individuals with Down syndrome have an extremely high risk of Alzheimer's disease (AD). Advances in understanding the pathophysiology of AD, and the development of effective therapies for individuals with sporadic AD, have raised the possibility that aging Down syndrome individuals may benefit from therapy directed against AD. As no prior large clinical trials had been conducted with this population, the authors launched "A Multicenter Trial of Vitamin E in Aging Individuals with Down Syndrome." The authors describe how they assembled an international group of investigators to develop the infrastructure and methodology for studying the efficacy of therapeutic interventions aimed at slowing the process of AD in Down syndrome. The process of designing and implementing the trial drew together clinical scientists and clinicians from two distinct but overlapping areas: researchers in the areas of Down syndrome and AD therapeutics. The authors review the issues considered and decisions made regarding various aspects of the trial design. [source] Issues in designing and interpreting clinical trials of treatments for chronic hepatitis CJOURNAL OF VIRAL HEPATITIS, Issue 2006C. O'Brien Summary., Many of the major advances in treating patients for chronic hepatitis C have been made based on the results of randomized, double-blind, controlled clinical trials. However, given the large number of hepatitis C medications in development, physicians need to understand the unique elements and types of clinical trials in order to make accurate comparisons of differing drug efficacy claims. Clinicians also need to be aware of the various factors that can influence the outcomes and interpretations of these trials, irrespective of the intervention under study. For example, similar trials conducted in the United States and Europe may have different outcomes simply because the study populations differ. Thus, both trial design and patient population are important considerations in the design and analysis of clinical trials for patients with chronic hepatitis C. [source] Defining disease-modifying therapies for PD,A road map for moving forward,MOVEMENT DISORDERS, Issue 12 2010C. Warren Olanow MD Abstract A disease-modifying therapy that slows or stops disease progression is one of the major unmet needs in the management of Parkinson's disease. To date, no therapy has been approved for disease modification despite promising laboratory data and positive results in clinical trials. This is because confounding symptomatic or pharmacologic effects cannot be excluded. The delayed start study provides an opportunity to define therapies that provide benefit that cannot be explained by an early symptomatic effect alone. However, this trial design does not necessarily provide a meaningful measure of the effect of the intervention on cumulative disability. In contrast, the long-term simple study provides a measure of the effect of the drug on cumulative disability but does not address mechanism of action. Together these two trials provide a road map for defining a disease modifying drug and determining the long term cumulative effect of the drug on the disease. © 2010 Movement Disorder Society [source] Are delayed-start design trials to show neuroprotection in Parkinson's disease fundamentally flawed?MOVEMENT DISORDERS, Issue 6 2008Carl E. Clarke BSc, FRCP Abstract Considerable effort has gone into preclinical neuroprotection research in Parkinson's disease (PD) and several large clinical trials have been mounted, but no agent has been conclusively shown to be protective. The latest innovation in PD neuroprotection trial design is the delayed-start design trial. If patients with early PD do better after 12 to 18 months of immediate drug therapy compared to those in whom it is delayed for 6 to 9 months, this is attributed to a neuroprotective effect. However, delayed-start design trials may be fundamentally flawed. It has been suggested that physiological mechanisms compensating for the loss of dopaminergic neurones in early PD may be deleterious and that immediate treatment may prevent such mechanisms and thereby be neuroprotective. If this hypothesis is correct, any drug with a symptomatic effect will be neuroprotective in early PD and delayed-start design trials will show this generic effect, not a neuroprotective effect specific to the drug. Delayed-start design trials require patients to potentially stay untreated for 6 to 9 months. This may lead to the selection of slowly progressive types of PD, such as that in younger patients and those with tremor-dominant disease, so the results may not be generalizable to the majority of patients. Delayed-start design trials are powered to find small differences in total UPDRS score which may not be clinically significant; larger and longer placebo-controlled trials are required to confirm the clinical significance of their findings. These arguments add to the growing tide of opinion for a fundamental rethink of our policy toward neuroprotection research in PD. © 2008 Movement Disorder Society [source] A "cure" for Parkinson's disease: Can neuroprotection be proven with current trial designs?MOVEMENT DISORDERS, Issue 5 2004Carl E. Clarke BSc Abstract Current medical and surgical therapies for Parkinson's disease provide symptomatic control of motor impairments rather than slowing or halting the progression of the disease. Previous clinical trials examining drugs such as dopamine agonists and selegiline for neuroprotective effects used "surrogate" outcomes, including clinical measures (rating scales, time to require levodopa), neuroimaging techniques (,-CIT single photon emission computed tomography; fluorodopa positron emission tomography), and mortality tracking. These studies failed to provide conclusive results because of design faults such as failing to control for symptomatic effects, small sample size, and not accounting for the possible effects of drugs on radionuclide tracer handling. Lessons must be learned from these failed neuroprotection trials. This review summarises the problems with previous neuroprotection studies and makes recommendations for future trial design. It is concluded that the primary outcome of explanatory trials should continue to be clinical measures such as the Unified Parkinson's Disease Rating Scale (UPDRS). It should be assumed that all agents have a symptomatic effect, which necessitates evaluation after a prolonged drug washout period. To achieve the evaluation after a prolonged drug washout period more effectively, trials must be performed in early disease and over a short period (6,12 months) so that symptomatic therapy is not required. To achieve adequate statistical power, these trials will need to include thousands of patients. Radionuclide imaging can only be used in such trials after considerable methodological work has been performed to establish its validity and reliability. To be affordable, such large explanatory trials need more streamlined designs with fewer hospital visits, fewer outcome measures, and rationalised safety monitoring. The clinical effectiveness of promising compounds from explanatory trials will need to be established in large long-term pragmatic trials using outcome measures such as quality of life, cost-effectiveness, and mortality. Such pragmatic trials could be continuations of the explanatory trials: after the primary outcome of the explanatory study (e.g., UPDRS) has been reported in an interim analysis, the trial could be continued for a further 5 to 10 years to report on quality of life and health economics outcomes. © 2004 Movement Disorder Society [source] Folic acid and orofacial clefts: a review of the evidenceORAL DISEASES, Issue 1 2010GL Wehby Orofacial clefts are common and burdensome birth defects with a complex genetic and environmental etiology. The contribution of nutritional factors and supplements to the etiology of orofacial clefts has long been theorized and studied. Multiple studies have evaluated the role of folic acid in the occurrence and recurrence of orofacial clefts, using observational and non-randomized interventional designs. While preventive effects of folic acid on orofacial clefts are commonly reported, the evidence remains generally inconsistent. This paper reviews the findings of the main studies of the effects of folic acid on orofacial clefts, summarizes study limitations, and discusses research needs with a focus on studying the effects of high dosage folic acid on the recurrence of oral clefts using a randomized clinical trial design. The role of folic acid in the prevention of neural tube defects is also briefly summarized and discussed as a reference model for orofacial clefts. [source] Psychological Intervention Following Implantation of an Implantable Defibrillator: A Review and Future RecommendationsPACING AND CLINICAL ELECTROPHYSIOLOGY, Issue 12 2007SUSANNE S. PEDERSEN Ph.D. Background:The medical benefits of the implantable cardioverter defibrillator (ICD) are unequivocal, but a subgroup of patients experiences emotional difficulties following implantation. For this subgroup, some form of psychological intervention may be warranted. This review provides an overview of current evidence on the efficacy of psychological intervention in ICD patients and recommendations for future research. Methods:We searched the PubMed and PsycInfo databases in the period between January 1980 and April 2007, using a set of a priori determined keywords. Based on the search and a hand search of the reference lists of the included articles, we identified nine studies that fulfilled the inclusion criteria. Results:The majority of studies used a randomized controlled trial design, but studies varied considerably in sample size, response, attrition rate, and type of intervention. However, most interventions were multifactorial, using cognitive behavioral therapy as one of the mainstays of treatment. Overall, psychological interventions seem to have little impact on shocks and heart rate variability. Some studies found a decrease in depressive symptoms and gains in quality of life, but the most notable effects are seen in improved exercise capacity and reductions in anxiety. Effect sizes for changes in anxiety in the intervention group ranged from small to large compared to small in the usual care group, using Cohen's effect size index. Conclusions:Preliminary evidence from small-scale intervention trials suggests that psychological intervention is worthwhile in ICD patients. Nevertheless, large-scale, well-designed trials are warranted to substantiate these findings. A multifactorial approach using a cognitive behavioral component paired with exercise training is likely to be the most successful. [source] Intravenous Magnesium for Complex Regional Pain Syndrome Type 1 (CRPS 1) Patients: A Pilot StudyPAIN MEDICINE, Issue 5 2009Susan Collins MSc ABSTRACT Objectives., To explore the feasibility of intravenous magnesium administration as a potential candidate intervention for a large size trial in Complex Regional Pain Syndrome Type 1 (CRPS 1). Design., Randomized clinical trial. Setting., Outpatient pain clinic. Patients., Ten CRPS 1 patients. Interventions., Eight patients received 70 mg/kg magnesium sulphate infusions in 4 hours for 5 days. For blinding purposes, 2 patients received equal amount NaCl 0.9% solutions (data not analyzed or presented). Interventions were accompanied by standardized physical therapy. Outcome Measures., Pain was assessed using an 11-point Box scale (three times daily for a week) and the McGill Pain Questionnaire. Skin sensitivity was measured with the Semmes Weinstein Monofilaments, (other) impairments with the Impairment Level Sumscore. In addition, functional limitations (Radboud Skills Questionnaire, questionnaire rising and sitting down) and quality of life (Short Form-36 [SF-36], EuroQol) were evaluated. Assessments were performed at baseline, 1, 3, 6, and 12 weeks after intervention. Results., Mild systemic side effects were experienced and the infusions were locally well tolerated. Pain was significantly reduced at all follow up compared with baseline (T1: P = 0.01, T3: P = 0.04, T6: P = 0.02, T12: P = 0.02). McGill sensory subscale improved significantly at T1 (number of words chosen: P = 0.03 and pain rating index: P = 0.03). Impairment level (P = 0.03) and quality of life (EuroQol P = 0.04, SF-36 physical P = 0.01) were significantly improved at T12. No improvement was found for skin sensitivity and functional limitations. Conclusion., Intravenous magnesium significantly improved pain, impairment and quality of life and was well tolerated. The results of this pilot study are encouraging and suggest that magnesium IV as a treatment in CRPS 1 should be further explored in a large size formal trial design. [source] Assessing the impact of ICH E9PHARMACEUTICAL STATISTICS: THE JOURNAL OF APPLIED STATISTICS IN THE PHARMACEUTICAL INDUSTRY, Issue 2 2008David Brown Abstract The ICH harmonized tripartite guideline ,Statistical Principles for Clinical Trials', more commonly referred to as ICH E9, was adopted by the regulatory bodies of the European Union, Japan and the USA in 1998. This document united related guidance documents on statistical methodology from each of the three ICH regions, and meant that for the first time clear consistent guidance on statistical principles was available to those conducting and reviewing clinical trials. At the 10th anniversary of the guideline's adoption, this paper discusses the influence of ICH E9 by presenting a perspective on how approaches to some aspects of clinical trial design, conduct and analysis have changed in that time in the context of regulatory submissions in the European Union. Copyright © 2008 John Wiley & Sons, Ltd. [source] A two-stage phase II trial design utilizing both primary and secondary endpointsPHARMACEUTICAL STATISTICS: THE JOURNAL OF APPLIED STATISTICS IN THE PHARMACEUTICAL INDUSTRY, Issue 2 2008Xun Lin Abstract Phase II trials in oncology drug development are usually conducted to perform the initial assessment of treatment activity. The common designs in this setting, for example, Simon 2-stage designs, are often developed based on testing whether a parameter of interest, usually a proportion (e.g. response rate), is less than a certain level or not. These designs usually consider only one parameter. However, sometimes we may encounter situations where we need to consider not a single parameter, but multiple parameters. This paper presents a two-stage design in which both primary and secondary endpoints are utilized in the decision rules. The family-wise Type 1 error rate and statistical power of the proposed design are investigated under a variety of situations by means of Monte-Carlo simulations. Copyright © 2007 John Wiley & Sons, Ltd. [source] | ||||||||||||||||||||||||||||||||||