DEVELOPING WORLD BIOETHICS, Issue 3 2007
JONATHAN KIMMELMAN
ABSTRACT Relatively little has been written about the ethics of conducting early phase clinical trials involving subjects from the developing world. Below, I analyze ethical issues surrounding one of gene transfer's most widely praised studies conducted to date: in this study, Italian investigators recruited two subjects from the developing world who were ineligible for standard of care because of economic considerations. Though the study seems to have rendered a cure in these two subjects, it does not appear to have complied with various international guidelines that require that clinical trials conducted in the developing world be responsive to their populations' health needs. Nevertheless, policies devised to address large scale, late stage trials, such as the AZT short-course placebo trials, map somewhat awkwardly to early phase studies. I argue that interest in conducting translational research in the developing world, particularly in the context of hemophilia trials, should motivate more rigorous ethical thinking around clinical trials involving economically disadvantaged populations. [source]

CLINICAL TRIALS ON THE USE OF WHITENING STRIPS IN CHILDREN AND ADOLESCENTS

JOURNAL OF ESTHETIC AND RESTORATIVE DENTISTRY, Issue 6 2005
K.J. Donly
ABSTRACT Objective: This article reported the cumulative findings from three controlled, randomized clinical trials evaluating the efficacy and tolerability of tooth whitening in children and adolescents using disposable polyethylene strip systems. Materials and Methods: The study population included 132 children and adolescents, ages 10 to 18 years. (Please note that 71 of these subjects were identified in the previous review.) Fifty-three percent of the subjects were female and 47% were male, with a mean age of 14.4 years. Subjects were divided into experimental treatment groups by balancing groups with respect to demographic characteristics and baseline tooth colors. Subiects were treated with either 5.3% or 6.5% hydrogen peroxide gel polyethylene strips. All subjects had to have all permanent anterior teeth erupted, a baseline Vita shade (Vita Zahnfabrik, Bad Säckingen, Germany) score of A2 or darker, and a desire that their teeth be whitened. One study included subjects who had previously received comprehensive orthodontic treatment. Digital images were collected for all subjects at baseline, 2 weeks, and 4 weeks. Oral examinations and interviews were conducted at each appointment to evaluate adverse events. Color change was calculated from the digital images in the same manner previously described. Results: The 5.3% and 6.5% hydrogen peroxide strips used for 30 minutes twice a day yielded significant tooth whitening (p < .0001) after 14 days. For the primary whitening parameter, ,b*, continued treatment during the 14- to 28-day period resulted in significant additional reduction in yellowness (p < .0001). Subjects treated with 6.5% hydrogen peroxide strips experienced significantly (p < .03) greater reduction in yellowness (approximately 0.8 ,b* units) compared with those who used the 5.3 hydrogen peroxide strips. The hydrogen peroxide strips were tolerated well in all of these studies, with minor tooth sensitivity and oral irritation being the primary complaints. Eighteen subjects (14%) reported oral irritation, whereas 30 subjects (23%) reported tooth sensitivity. All adverse events were relieved upon discontinuance of product use. Conclusion: The 5.3% and 6.5% hydrogen peroxide gel strips used for 30 minutes twice a day effectively whitened teeth, and both regimens were well tolerated. [source]

A COMPARISON OF THE IMPRECISE BETA CLASS, THE RANDOMIZED PLAY-THE-WINNER RULE AND THE TRIANGULAR TEST FOR CLINICAL TRIALS WITH BINARY RESPONSES

AUSTRALIAN & NEW ZEALAND JOURNAL OF STATISTICS, Issue 1 2007
Lyle C. Gurrin
Summary This paper develops clinical trial designs that compare two treatments with a binary outcome. The imprecise beta class (IBC), a class of beta probability distributions, is used in a robust Bayesian framework to calculate posterior upper and lower expectations for treatment success rates using accumulating data. The posterior expectation for the difference in success rates can be used to decide when there is sufficient evidence for randomized treatment allocation to cease. This design is formally related to the randomized play-the-winner (RPW) design, an adaptive allocation scheme where randomization probabilities are updated sequentially to favour the treatment with the higher observed success rate. A connection is also made between the IBC and the sequential clinical trial design based on the triangular test. Theoretical and simulation results are presented to show that the expected sample sizes on the truly inferior arm are lower using the IBC compared with either the triangular test or the RPW design, and that the IBC performs well against established criteria involving error rates and the expected number of treatment failures. [source]

Follow-Up of 1 mg Finasteride Treatment of Male Pattern Baldness,Difference between Clinical Trials and Private Office Follow-Up: Influences on Prescribing Habits Evaluated

DERMATOLOGIC SURGERY, Issue 5 2004
Marvin J. Rapaport MD
Background. Finasteride (Propecia) was approved by the FDA in 1998 for treating men with androgenetic alopecia. The published clinical trials demonstrated statistical differences between drug and placebo. Rarely do new drugs undergo further non-drug-company-sponsored studies of efficacy. Concerns about clinical studies and marketing of drugs prompted this evaluation of a large group of patients taking this medication. Objective. Finasteride usage offered an opportunity not only to understand the acceptance of a cosmetically oriented medication, but also to evaluate subjective comments and compliance after a long period of time. Methods. A total of 1261 patients were monitored with phone calls every 3 months after finasteride was initially prescribed. After 12 months, a detailed questionnaire was sent to all patients with an additional letter and two telephone calls if no response was received. Statistical analysis of the patients' data was made. Results. Thirty-two percent or 414 men continued to take finasteride daily for 1 to 3 years. Twenty-four percent or 297 men discontinued the drug between 3 and 15 months owing to poor results. The remaining 44% or 549 men were lost to follow-up despite numerous attempts to contact them. Conclusion. A total of 414 men continued to take the medication, but only 211 returned detailed questionnaires. A small percentage of this group felt that they grew hair. The remaining patients noted poor results. [source]

Reporting Clinical Trials: Full Access to All the Data

EPILEPSIA, Issue 12 2001
Article first published online: 11 JAN 200
No abstract is available for this article. [source]

Quantitative Assessment of Seizure Severity for Clinical Trials: A Review of Approaches to Seizure Components

EPILEPSIA, Issue 1 2001
Joyce A. Cramer
Summary: Quantitative assessment of seizure severity has been approached using a variety of systems. This review describes currently available methods and possible new approaches to seizure assessment for clinical trials. A review of the literature on methods of seizure assessments resulted in tabulation of the seizure rating scales known as VA, Chalfont-National Hospital, Liverpool, Hague, and the Occupational Hazard Scale. Seizures have been evaluated by simply counting all events, counting events by type, by clinician ratings, patient ratings, and combinations. Each of the scales has advantages and disadvantages. Most scales share core components: seizure frequency, seizure type, seizure duration, postictal events, postictal duration, automatisms, seizure clusters, known patterns, warnings, tongue biting, incontinence, injuries, and functional impairment. This review revealed a partial consensus about aspects of seizures that are important markers for severity. However, usefulness of the existing scales is limited by lack of data on responsiveness. New approaches are needed to assess changes in seizure severity as a result of an intervention in a clinical trial. [source]

Almotriptan Increases Pain-Free Status in Patients With Acute Migraine Treated in Placebo-Controlled Clinical Trials

HEADACHE, Issue 2002
FRCP(C), Ninan T. Mathew MD
Objectives.,Evaluate the efficacy of a single oral dose of almotriptan in achieving pain-free status during treatment of acute migraine attacks. Methods.,This pooled analysis (N=1321) used data from two randomized, placebo-controlled, phase III trials (studies A and B) to determine the proportion of patients with migraine achieving pain-free status 2 hours after a single oral dose of study medication (almotriptan or placebo). Pain was assessed using a 4-point integer scale (0=no headache, 3=severe headache), and recorded in a patient self-assessment booklet. Results.,The proportion of patients pain-free at 2 hours after study medication was significantly greater with almotriptan 6.25 mg (both studies P,.002) and almotriptan 12.5 mg (both studies P,.001) than with placebo. In study A, 11.6% of patients taking almotriptan 12.5 mg versus 2.5% of patients receiving placebo were pain-free at 1 hour (P=.016). At 1.5 hours, 26.8% of patients taking almotriptan 12.5 mg versus 8.8% receiving placebo (P=.001) were pain-free, and at 2 hours, 38.4% on almotriptan versus 11.3% on placebo were pain-free (P<.001). In study B, 23.8% of patients taking almotriptan 12.5 mg were free from pain at 1.5 hours versus 10.2% receiving placebo (P<.001). At 2 hours, 39.2% taking almotriptan 12.5 mg versus 15.3% receiving placebo were pain-free (P<.001). Increases in pain-free status with almotriptan generally occurred in a dose-dependent manner. Conclusion.,Compared with placebo, almotriptan 12.5 mg significantly increases the proportion of patients who are pain-free by as early as 1 hour, and consistently by 1.5 hours, after a single dose. [source]

Patient and clinician collaboration in the design of a national randomized breast cancer trial

HEALTH EXPECTATIONS, Issue 1 2004
Jo 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]

Statistics Applied to Clinical Trials, Fourth Edition by Ton J. Cleophas, Aeilko H. Zwinderman, Toine F. Cleophas, Eugene P. Cleophas

INTERNATIONAL STATISTICAL REVIEW, Issue 3 2009
Andreas Rosenblad
No abstract is available for this article. [source]

Adaptive Design Methods in Clinical Trials by Shein-Chung Chow, Mark Chang

INTERNATIONAL STATISTICAL REVIEW, Issue 2 2007
C.M. O'Brien
No abstract is available for this article. [source]

Encouraging Cancer Patients to Talk to Their Physicians About Clinical Trials: Considering Patients' Information Needs,

JOURNAL OF APPLIED BIOBEHAVIORAL RESEARCH, Issue 3-4 2007
Amy E. Latimer
This study examined the effectiveness of detailed and nondetailed information for encouraging cancer patients to discuss clinical trials with their physicians. We hypothesized that detailed messages would lead to greater understanding of clinical trials and increased intentions and likelihood of broaching the topic with a physician, especially among individuals high in need for cognition (NFC). Participants (448 cancer patients) (a) completed a baseline assessment of understanding and intentions, (b) received either detailed or nondetailed messages, and (c) completed follow-up assessments at Weeks 1 and 6. The detailed messages led to greater intentions to discuss clinical trials than nondetailed messages among low-NFC participants. High-NFC participants' understanding, intentions, and behavior were not differentially affected by the detailed message. [source]

When the Clinical Trials Raise More Questions Than Answers: Blood Pressure Controversy Beyond the TRANSCEND Results

JOURNAL OF CLINICAL HYPERTENSION, Issue 3 2009
Vivencio Barrios MD
No abstract is available for this article. [source]

Update on the Management of Hypertension: Recent Clinical Trials and the JNC 7

JOURNAL OF CLINICAL HYPERTENSION, Issue 2004
Marvin Moser MD Editor in Chief
The following issues are highlighted: Emphasis is placed on the importance of systolic blood pressure elevations in estimating risk and in determining prognosis. A review of placebo-controlled clinical trials indicates that cardiovascular events are statistically significantly reduced with diuretic- or , blocker-based treatment regimens. The question of whether blood pressure lowering alone or specific medications make the difference in outcome is discussed. Based on the results of numerous trials, it is apparent that blood pressure lowering itself is probably of greater importance in reducing cardiovascular events than the specific medication used. Meta-analyses suggest, however, that the use of an agent that blocks the renin-angiotensin aldosterone system is probably more effective in diabetics and in patients with nephropathy than a regimen based on calcium channel blocker therapy. The Antihypertensive and Lipid-Lowering treatment to Prevent Heart Attack Trial (ALLHAT) reported no overall difference in coronary heart disease outcome among patients treated with a diuretic-based compared to a calcium channel blocker- or an angiotensin-converting enzyme inhibitor-based treatment program. However, patients in the diuretic group experienced fewer episodes of heart failure than in the calcium channel blocker group and fewer episodes of heart failure and strokes than those in the angiotensin-converting enzyme inhibitor group. Results were similar in diabetics and nondiabetics. Possible reasons for this outcome are discussed. The Australian National Blood Pressure 2 study, which was unblinded, reported a marginally significantly better outcome only in male patients receiving an angiotensin-converting enzyme inhibitor-based regimen compared to those receiving a diuretic-based program. Finally, the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) is reviewed. Highlights of this report include the new designation of prehypertension, i.e., blood pressures of 120,139 mm Hg/80,89 mm Hg. The JNC 7 suggested that diuretics should be the first-step drug of choice in most patients, but listed numerous specific reasons why other agents should be used in special situations. The report stressed that the majority of patients will require two or more medications to achieve goal blood pressure. [source]

Revised STandards for Reporting Interventions in Clinical Trials of Acupuncture (STRICTA): Extending the CONSORT Statement

JOURNAL OF EVIDENCE BASED MEDICINE, Issue 3 2010
Hugh MacPherson
The STandards for Reporting Interventions in Clinical Trials of Acupuncture (STRICTA) were published in five journals in 2001 and 2002. These guidelines, in the form of a checklist and explanations for use by authors and journal editors, were designed to improve reporting of acupuncture trials, particularly the interventions, thereby facilitating their interpretation and replication. Subsequent reviews of the application and impact of STRICTA have highlighted the value of STRICTA as well as scope for improvements and revision. To manage the revision process a collaboration between the STRICTA Group, the CONSORT Group, and the Chinese Cochrane Centre was developed in 2008. An expert panel with 47 participants was convened that provided electronic feedback on a revised draft of the checklist. At a subsequent face-to-face meeting in Freiburg, a group of 21 participants further revised the STRICTA checklist and planned dissemination. The new STRICTA checklist, which is an official extension of CONSORT, includes six items and 17 sub-items. These set out reporting guidelines for the acupuncture rationale, the details of needling, the treatment regimen, other components of treatment, the practitioner background, and the control or comparator interventions. In addition, and as part of this revision process, the explanations for each item have been elaborated, and examples of good reporting for each item are provided. In addition, the word "controlled" in STRICTA is replaced by "clinical," to indicate that STRICTA is applicable to a broad range of clinical evaluation designs, including uncontrolled outcome studies and case reports. It is intended that the revised STRICTA, in conjunction with both the main CONSORT Statement and extension for nonpharmacologic treatment, will raise the quality of reporting of clinical trials of acupuncture. [source]

Prospective Registration of Clinical Trials in India: Strategies, Achievements & Challenges

JOURNAL OF EVIDENCE BASED MEDICINE, Issue 1 2009
Prathap 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]

Issues facing clinical trials of the future

JOURNAL OF INTERNAL MEDICINE, Issue 5 2003
R. M. Califf
Abstract. Califf RM (Duke University Medical Center, Durham, NC, USA). Issues facing clinical trials of the future (Clinical Trials). J Intern Med 2003; 254: 426,433. Diagnostic and therapeutic technology continues to advance rapidly, as does our knowledge of therapeutics and of clinical research methods. Unfortunately, these advances have been only poorly coupled with our knowledge of therapeutic principles, leading to increasing uncertainty about which technologies are truly effective and, amongst those that are effective, which are most effective for the cost. This article presents general principles derived from several investigators' experiences with clinical trials, and uses them to suggest how future clinical trials may differ from current approaches. A proposed organization for future trials also is elucidated. [source]

The evolution of the randomized controlled trial and its role in evidence-based decision making

JOURNAL OF INTERNAL MEDICINE, Issue 2 2003
P. J. Devereaux
Abstract., Devereaux PJ, Yusuf S (McMaster University, Hamilton, Ontario, Canada). The evolution of the randomized controlled trial and its role in evidence-based decision making (Clinical Trials). J Intern Med 2003; 254: 105,113. The randomized controlled trial has been used in medical research for a little over half a century. This manuscript provides an overview of some of the history and evolution of the randomized controlled trial during this period. There exists hierarchies of evidence for therapeutic, diagnostic and prognostic questions, and the randomized controlled trial is at the top of the therapeutic hierarchy. Despite being at the top of the therapeutic hierarchy randomization in itself does not guarantee the trial results approximate the true effect. Issues that result in systematic and nonsystematic deviations from the truth in randomized controlled trials must also be considered. We present a model for evidence-based decision making that includes the following components: the clinical state, patient preferences, research evidence from a range of studies and clinical expertise. We discuss the role of the randomized controlled trial within evidence-based decision making. [source]

Timing of Death and Myocardial Infarction in Patients with Non-ST Elevation Acute Coronary Syndromes: Insights From Randomized Clinical Trials

JOURNAL OF INTERVENTIONAL CARDIOLOGY, Issue 5 2007
M.S., RAJENDRA H. MEHTA M.D.
Background: Adverse events occur following non-ST elevation acute coronary syndromes (NSTE ACS). However, the timing of these events in relation to index event is less clear. Methods: Accordingly, we evaluated 26,466 NSTE ACS patients from the Global Use of Strategies to Open Occluded Arteries in Acute Coronary Syndromes (GUSTO-IIb), Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy (PURSUIT), and Platelet IIb/IIIa Antagonism for the Reduction of Acute Coronary Syndrome Events in a Global Organization Network (PARAGON) A and B trials to ascertain the timing of adverse events. Outcomes of interest were death, myocardial infarction (MI), and death or MI at 180 days. Logistic regression modeling for death was used to categorize patients into low-, medium-, and high-risk groups. Results: At 6 months, 6.2% of patients died, 12.1% had MI, and 15.7% suffered death or MI. From 15% to 40% of these events occurred beyond 30 days. At 6 months, 3%, 4%, and 13% of patients died in low-, medium-, and high-risk groups, respectively. However, the proportion of patients dying beyond 30 days was similar in the three groups (44%, 43%, and 41% of death, respectively). Similarly, whereas death or MI increased with higher risk (11%, 14%, and 23%, respectively), the proportion of patients with this event beyond 30 days did not differ in the three strata (22%, 20%, and 25%, respectively). Conclusions: Our study provides important insights into the timing of adverse events and suggests that the substantial proportion of patients suffer subsequent adverse events after their index NSTE ACS. Thus, these data call for continuous surveillance for these events and efforts beyond the acute phase at increasing adherence to evidence-based therapies to improve the outcomes of these patients. [source]

Randomized Controlled Clinical Trials

JOURNAL OF PAEDIATRICS AND CHILD HEALTH, Issue 2 2003
CH Cole
No abstract is available for this article. [source]

Review article: rifaximin, a minimally absorbed oral antibacterial, for the treatment of travellers' diarrhoea

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 11 2010
P. LAYER
Aliment Pharmacol Ther,31, 1155,1164 Summary Background, Travellers' diarrhoea, a common problem worldwide with significant medical impact, is generally treated with anti-diarrhoeal agents and fluid replacement. Systemic antibiotics are also used in selected cases, but these may be associated with adverse effects, bacterial resistance and drug,drug interactions. Aim, To review the clinical evidence supporting the efficacy and safety of the minimally absorbed oral antibiotic rifaximin in travellers' diarrhoea. Methods, PubMed and the Cochrane Register of Controlled Clinical Trials (to January 2010) and International Society of Travel Medicine congress abstracts (2003,2009) were searched to identify relevant publications. Results, A total of 10 publications were included in the analysis. When administered three times daily for 3 days, rifaximin is superior to placebo or loperamide; it is at least as effective as ciprofloxacin in reducing duration of illness and restoring wellbeing in patients with travellers' diarrhoea, both with and without identification of a pathogen, as well as in diarrhoea caused by Escherichia coli infection. Rifaximin demonstrates only minimal potential for development of bacterial resistance and for cytochrome P450-mediated drug,drug interactions, and its tolerability profile is similar to that of placebo. Conclusion, When antibiotic therapy is warranted in uncomplicated travellers' diarrhoea, rifaximin may be considered as a first-line treatment option because of its favourable efficacy, tolerability and safety profiles. [source]

Adaptive Design Methods in Clinical Trials

JOURNAL OF THE ROYAL STATISTICAL SOCIETY: SERIES A (STATISTICS IN SOCIETY), Issue 1 2008
Angela Wade
No abstract is available for this article. [source]

Statistical issues in first-in-man studies

JOURNAL OF THE ROYAL STATISTICAL SOCIETY: SERIES A (STATISTICS IN SOCIETY), Issue 3 2007
Professor Stephen Senn
Preface., In March 2006 a first-in-man trial took place using healthy volunteers involving the use of monoclonal antibodies. Within hours the subjects had suffered such adverse effects that they were admitted to intensive care at Northwick Park Hospital. In April 2006 the Secretary of State for Health announced the appointment of Professor (now Sir) Gordon Duff, who chairs the UK's Commission on Human Medicines, to chair a scientific expert group on phase 1 clinical trials. The group reported on December 7th, 2006 (Expert Scientific Group on Clinical Trials, 2006a). Clinical trials have a well-established regulatory basis both in the UK and worldwide. Trials have to be approved by the regulatory authority and are subject to a detailed protocol concerning, among other things, the study design and statistical analyses that will form the basis of the evaluation. In fact, a cornerstone of the regulatory framework is the statistical theory and methods that underpin clinical trials. As a result, the Royal Statistical Society established an expert group of its own to look in detail at the statistical issues that might be relevant to first-in-man studies. The group mainly comprised senior Fellows of the Society who had expert knowledge of the theory and application of statistics in clinical trials. However, the group also included an expert immunologist and clinicians to ensure that the interface between statistics and clinical disciplines was not overlooked. In addition, expert representation was sought from Statisticians in the Pharmaceutical Industry (PSI), an organization with which the Royal Statistical Society has very close links. The output from the Society's expert group is contained in this report. It makes a number of recommendations directed towards the statistical aspects of clinical trials. As such it complements the report by Professor Duff's group and will, I trust, contribute to a safer framework for first-in-man trials in the future. Tim Holt (President, Royal Statistical Society) [source]

Clinical Trials: a Methodological Perspective, 2nd edn by S. Piantadosi

JOURNAL OF THE ROYAL STATISTICAL SOCIETY: SERIES A (STATISTICS IN SOCIETY), Issue 1 2007
J. Wade Davis
No abstract is available for this article. [source]

Quality of Reporting of Clinical Trials of Dogs and Cats and Associations with Treatment Effects

JOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 1 2010
J.M. Sargeant
Background: To address concerns about the quality of reporting of randomized controlled trials, and the potential for biased treatment effects in poorly reported trials, medical journals have adopted a common set of reporting guidelines, the Consolidated Standards of Reporting Trials (CONSORT) statement, to improve the reporting of randomized controlled trials. Hypothesis: The reporting of clinical trials involving dogs and cats might not be ideal, and this might be associated with biased treatment effects. Animals: Dogs and cats used in 100 randomly selected reports of clinical trials. Methods: Data related to methodological quality and completeness of reporting were extracted from each trial. Associations between reporting of trial features and the proportion of positive treatment effects within trials were evaluated by generalized linear models. Results: There were substantive deficiencies in reporting of key trial features. An increased proportion of positive treatment effects within a trial was associated with not reporting: the method used to generate the random allocation sequence (P < .001), the use of double blinding (P < .001), the inclusion criteria for study subjects (P= .003), baseline differences between treatment groups (P= .006), the measurement used for all outcomes (P= .002), and possible study limitations (P= .03). Conclusions and Clinical Importance: Many clinical trials involving dogs and cats in the literature do not report details related to methodological quality and aspects necessary to evaluate external validity. There is some evidence that these deficiencies are associated with treatment effects. There is a need to improve reporting of clinical trials, and guidelines, such as the CONSORT statement, can provide a valuable tool for meeting this need. [source]

Editorial: Perils and Pitfalls of Clinical Trials,Experience from Human Oncology

JOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 4 2000
FRANZCR, Graham Pitson MBBS
No abstract is available for this article. [source]

NIH Conference on Estrogen and Progestin Clinical Trials

NURSING FOR WOMENS HEALTH, Issue 1 2003
Shelagh Roberts
No abstract is available for this article. [source]

Search for the Optimal Right Ventricular Pacing Site: Design and Implementation of Three Randomized Multicenter Clinical Trials

PACING AND CLINICAL ELECTROPHYSIOLOGY, Issue 4 2009
GERRY KAYE M.D.
Background: The optimal site to permanently pace the right ventricle (RV) has yet to be determined. To address this issue, three randomized prospective multicenter clinical trials are in progress comparing the long-term effects of RV apical versus septal pacing on left ventricular (LV) function. The three trials are Optimize RV Selective Site Pacing Clinical Trial (Optimize RV), Right Ventricular Apical and High Septal Pacing to Preserve Left Ventricular Function (Protect Pace), and Right Ventricular Apical versus Septal Pacing (RASP). Methods: Patients that require frequent or continuous ventricular pacing are randomized to RV apical or septal pacing. Optimize RV excludes patients with LV ejection fraction <40% prior to implantation, whereas the other trials include patients regardless of baseline LV systolic function. The RV septal lead is positioned in the mid-septum in Optimize RV, the high septum in Protect Pace, and the mid-septal inflow tract in RASP. Lead position is confirmed by fluoroscopy in two planes and adjudicated by a blinded panel. The combined trials will follow approximately 800 patients for up to 3 years. Results: The primary outcome in each trial is LV ejection fraction evaluated by radionuclide ventriculography or echocardiography. Secondary outcomes include echo-based measurements of ventricular/atrial remodeling, 6-minute hall walk distance, brain natriuretic peptide levels, and clinical events (atrial tachyarrhythmias, heart failure, stroke, or death). Conclusion: These selective site ventricular pacing trials should provide evidence of the importance of RV pacing site in the long-term preservation of LV function in patients that require ventricular pacing and help to clarify the optimal RV pacing site. [source]

painACTION-Back Pain: A Self-Management Website for People with Chronic Back Pain

PAIN MEDICINE, Issue 7 2010
Emil Chiauzzi PhD
Abstract Objective., To determine whether an interactive self-management Website for people with chronic back pain would significantly improve emotional management, coping, self-efficacy to manage pain, pain levels, and physical functioning compared with standard text-based materials. Design., The study utilized a pretest,posttest randomized controlled design comparing Website (painACTION-Back Pain) and control (text-based material) conditions at baseline and at 1-, 3, and 6-month follow-ups. Participants., Two hundred and nine people with chronic back pain were recruited through dissemination of study information online and at a pain treatment clinic. The 6-month follow-up rates for the Website and control groups were 73% and 84%, respectively. Measurements., Measures were based on the recommendations of the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials and included measures of pain intensity, physical functioning, emotional functioning, coping, self-efficacy, fear-avoidance, perceived improvement with treatment, self-efficacy, and catastrophizing. Results., Compared with controls, painACTION-Back Pain participants reported significantly: 1) lower stress; 2) increased coping self-statements; and 3) greater use of social support. Comparisons between groups suggested clinically significant differences in current pain intensity, depression, anxiety, stress, and global ratings of improvement. Among participants recruited online, those using the Website reported significantly: 1) lower "worst" pain; 2) lower "average" pain; and 3) increased coping self-statements, compared with controls. Participants recruited through the pain clinic evidenced no such differences. Conclusions., An online self-management program for people with chronic back pain can lead to improvements in stress, coping, and social support, and produce clinically significant differences in pain, depression, anxiety, and global rates of improvement. [source]

Professional development of statisticians in the pharmaceutical sector: evolution over the past decade and into the future

PHARMACEUTICAL STATISTICS: THE JOURNAL OF APPLIED STATISTICS IN THE PHARMACEUTICAL INDUSTRY, Issue 3 2008
Trevor Lewis CStat
Abstract The adoption of The International Conference on Harmonization Tripartite Guideline: Statistical Principles for Clinical Trials (ICH-E9) has provided a foundation for the application of statistical principles in clinical research and raised awareness of the value of a statistical contribution to the wider pharmaceutical R&D process. In addition, over the past decade globalization of the pharmaceutical R&D process and the measures taken to address reduced productivity and spiralling costs have impacted on the roles and career opportunities for statisticians working in the pharmaceutical sector. This has enhanced the need for continuing professional development to equip statisticians with the skills to fully contribute to creating innovative solutions. In the future, key areas of focus are the establishment of professional standards for statistical work and increasing the collaboration between statisticians working in industry, regulatory agencies and academia. In addition, the diversity of roles and potential career paths for statisticians embarking on a career in the pharmaceutical sector emphasizes the importance of mentoring and coaching. For the more experienced statisticians, there are unprecedented opportunities to lead and innovate. Copyright © 2008 John Wiley & Sons, Ltd. [source]

Who wants to be an ICH Euro billionaire?

PHARMACEUTICAL STATISTICS: THE JOURNAL OF APPLIED STATISTICS IN THE PHARMACEUTICAL INDUSTRY, Issue 1 2008
Kerry Gordon
Abstract The ICH E9 guideline on Statistical Principles for Clinical Trials is a pivotal document for statisticians in clinical research in the pharmaceutical industry guiding, as it does, statistical aspects of the planning, conduct and analysis of regulatory clinical trials. New statisticians joining the industry require a thorough and lasting understanding of the 39-page guideline. Given the amount of detail to be covered, traditional (lecture-style) training methods are largely ineffective. Directed reading, perhaps in groups, may be a helpful approach, especially if experienced staff are involved in the discussions. However, as in many training scenarios, exercise-based training is often the most effective approach to learning. In this paper, we describe several variants of a training module in ICH E9 for new statisticians, combining directed reading with a game-based exercise, which have proved to be highly effective and enjoyable for course participants. Copyright © 2007 John Wiley & Sons, Ltd. [source]