Control and the Therapeutic Trial


Book Description

Listen to podcast with the author How do doctors decide whether their drugs, or other treatments, actually work? In practice this can be fiendishly difficult. Nowadays the gold standard is the randomised controlled trial (RCT). But the RCT is a recent invention, and the story of how it came to dominate therapeutic evaluation from the latter half of the twentieth century involves acrimony, confrontation, and manipulation of the powerful rhetoric of ‘control’. Control and the Therapeutic Trial examines the development of the RCT from the eclectic collection of methodologies available to practitioners in the early-twentieth century. In particular, it explores the British Medical Research Council’s (MRC) exploitation of the term ‘controlled’ to help establish its own ‘controlled trials’ as the gold standard for therapeutic evaluation, and, ultimately, the MRC itself as the proper authority to adjudicate on therapeutic efficacy. This rhetorical power still clings, and is exploited today. Control and the Therapeutic Trial will be of interest not only to historians of twentieth-century medicine and practising clinicians who take therapeutic decisions, but to anyone who seeks a broader insight into the forces that shaped, and control, the modern controlled trial.




Small Clinical Trials


Book Description

Clinical trials are used to elucidate the most appropriate preventive, diagnostic, or treatment options for individuals with a given medical condition. Perhaps the most essential feature of a clinical trial is that it aims to use results based on a limited sample of research participants to see if the intervention is safe and effective or if it is comparable to a comparison treatment. Sample size is a crucial component of any clinical trial. A trial with a small number of research participants is more prone to variability and carries a considerable risk of failing to demonstrate the effectiveness of a given intervention when one really is present. This may occur in phase I (safety and pharmacologic profiles), II (pilot efficacy evaluation), and III (extensive assessment of safety and efficacy) trials. Although phase I and II studies may have smaller sample sizes, they usually have adequate statistical power, which is the committee's definition of a "large" trial. Sometimes a trial with eight participants may have adequate statistical power, statistical power being the probability of rejecting the null hypothesis when the hypothesis is false. Small Clinical Trials assesses the current methodologies and the appropriate situations for the conduct of clinical trials with small sample sizes. This report assesses the published literature on various strategies such as (1) meta-analysis to combine disparate information from several studies including Bayesian techniques as in the confidence profile method and (2) other alternatives such as assessing therapeutic results in a single treated population (e.g., astronauts) by sequentially measuring whether the intervention is falling above or below a preestablished probability outcome range and meeting predesigned specifications as opposed to incremental improvement.




The Prevention and Treatment of Missing Data in Clinical Trials


Book Description

Randomized clinical trials are the primary tool for evaluating new medical interventions. Randomization provides for a fair comparison between treatment and control groups, balancing out, on average, distributions of known and unknown factors among the participants. Unfortunately, these studies often lack a substantial percentage of data. This missing data reduces the benefit provided by the randomization and introduces potential biases in the comparison of the treatment groups. Missing data can arise for a variety of reasons, including the inability or unwillingness of participants to meet appointments for evaluation. And in some studies, some or all of data collection ceases when participants discontinue study treatment. Existing guidelines for the design and conduct of clinical trials, and the analysis of the resulting data, provide only limited advice on how to handle missing data. Thus, approaches to the analysis of data with an appreciable amount of missing values tend to be ad hoc and variable. The Prevention and Treatment of Missing Data in Clinical Trials concludes that a more principled approach to design and analysis in the presence of missing data is both needed and possible. Such an approach needs to focus on two critical elements: (1) careful design and conduct to limit the amount and impact of missing data and (2) analysis that makes full use of information on all randomized participants and is based on careful attention to the assumptions about the nature of the missing data underlying estimates of treatment effects. In addition to the highest priority recommendations, the book offers more detailed recommendations on the conduct of clinical trials and techniques for analysis of trial data.




Smart Health Choices


Book Description

Every day we make decisions about our health - some big and some small. What we eat, how we live and even where we live can affect our health. But how can we be sure that the advice we are given about these important matters is right for us? This book will provide you with the right tools for assessing health advice.




Developing a Protocol for Observational Comparative Effectiveness Research: A User's Guide


Book Description

This User’s Guide is a resource for investigators and stakeholders who develop and review observational comparative effectiveness research protocols. It explains how to (1) identify key considerations and best practices for research design; (2) build a protocol based on these standards and best practices; and (3) judge the adequacy and completeness of a protocol. Eleven chapters cover all aspects of research design, including: developing study objectives, defining and refining study questions, addressing the heterogeneity of treatment effect, characterizing exposure, selecting a comparator, defining and measuring outcomes, and identifying optimal data sources. Checklists of guidance and key considerations for protocols are provided at the end of each chapter. The User’s Guide was created by researchers affiliated with AHRQ’s Effective Health Care Program, particularly those who participated in AHRQ’s DEcIDE (Developing Evidence to Inform Decisions About Effectiveness) program. Chapters were subject to multiple internal and external independent reviews. More more information, please consult the Agency website: www.effectivehealthcare.ahrq.gov)




Validity and Inter-Rater Reliability Testing of Quality Assessment Instruments


Book Description

The internal validity of a study reflects the extent to which the design and conduct of the study have prevented bias(es). One of the key steps in a systematic review is assessment of a study's internal validity, or potential for bias. This assessment serves to: (1) identify the strengths and limitations of the included studies; (2) investigate, and potentially explain heterogeneity in findings across different studies included in a systematic review; and (3) grade the strength of evidence for a given question. The risk of bias assessment directly informs one of four key domains considered when assessing the strength of evidence. With the increase in the number of published systematic reviews and development of systematic review methodology over the past 15 years, close attention has been paid to the methods for assessing internal validity. Until recently this has been referred to as “quality assessment” or “assessment of methodological quality.” In this context “quality” refers to “the confidence that the trial design, conduct, and analysis has minimized or avoided biases in its treatment comparisons.” To facilitate the assessment of methodological quality, a plethora of tools has emerged. Some of these tools were developed for specific study designs (e.g., randomized controlled trials (RCTs), cohort studies, case-control studies), while others were intended to be applied to a range of designs. The tools often incorporate characteristics that may be associated with bias; however, many tools also contain elements related to reporting (e.g., was the study population described) and design (e.g., was a sample size calculation performed) that are not related to bias. The Cochrane Collaboration recently developed a tool to assess the potential risk of bias in RCTs. The Risk of Bias (ROB) tool was developed to address some of the shortcomings of existing quality assessment instruments, including over-reliance on reporting rather than methods. Several systematic reviews have catalogued and critiqued the numerous tools available to assess methodological quality, or risk of bias of primary studies. In summary, few existing tools have undergone extensive inter-rater reliability or validity testing. Moreover, the focus of much of the tool development or testing that has been done has been on criterion or face validity. Therefore it is unknown whether, or to what extent, the summary assessments based on these tools differentiate between studies with biased and unbiased results (i.e., studies that may over- or underestimate treatment effects). There is a clear need for inter-rater reliability testing of different tools in order to enhance consistency in their application and interpretation across different systematic reviews. Further, validity testing is essential to ensure that the tools being used can identify studies with biased results. Finally, there is a need to determine inter-rater reliability and validity in order to support the uptake and use of individual tools that are recommended by the systematic review community, and specifically the ROB tool within the Evidence-based Practice Center (EPC) Program. In this project we focused on two tools that are commonly used in systematic reviews. The Cochrane ROB tool was designed for RCTs and is the instrument recommended by The Cochrane Collaboration for use in systematic reviews of RCTs. The Newcastle-Ottawa Scale is commonly used for nonrandomized studies, specifically cohort and case-control studies.




Textbook of Clinical Trials


Book Description

Now published in its Second Edition, the Textbook of Clinical Trials offers detailed coverage of trial methodology in diverse areas of medicine in a single comprehensive volume. Praise for the First Edition: "... very useful as an introduction to clinical research, or for those planning specific studies within therapeutic or disease areas." BRITISH JOURNAL OF SURGERY, Vol. 92, No. 2, February 2005 The book’s main concept is to describe the impact of clinical trials on the practice of medicine. It separates the information by therapeutic area because the impact of clinical trials, the problems encountered, and the numbers of trials in existence vary tremendously from specialty to specialty. The sections provide a background to the disease area and general clinical trial methodology before concentrating on particular problems experienced in that area. Specific examples are used throughout to address these issues. The Textbook of Clinical Trials, Second Edition: Highlights the various ways clinical trials have influenced the practice of medicine in many therapeutic areas Describes the challenges posed by those conducting clinical trials over a range of medical specialities and allied fields Additional therapeutic areas are included in this Second Edition to fill gaps in the First Edition as the number and complexity of trials increases in this rapidly developing area Newly covered or updated in the Second Edition: general surgery, plastic surgery, aesthetic surgery, palliative care, primary care, anaesthesia and pain, transfusion, wound healing, maternal and perinatal health, early termination, organ transplants, ophthalmology, epilepsy, infectious disease, neuro-oncology, adrenal, thyroid and urological cancers, as well as a chapter on the Cochrane network An invaluable resource for pharmaceutical companies, the Textbook of Clinical Trials, Second Edition appeals to those working in contract research organizations, medical departments and in the area of public health and health science alike.




Advanced Therapy of Inflammatory Bowel Disease


Book Description

Now published in two volumes to accommodate new chapters on the many advances in understanding and treatment options, this volume represents the definitive reference on inflammatory bowel disease, a spectrum of diseases that is receiving increasing attention as our understanding of the etiological factors increases and diagnostic tools are refined. Basic research accelerated at the beginning of this decade and is now yielding new, more targeted treatments than were available just a few years ago. Volume 1 is on IBD and Ulcerative Colitis, and Volume 2 is on IBD and Crohn's Disease. All areas that were covered in the second edition have been expanded and updated. New sections include one addressing etiology and pathophysiology of IBD, including environmental influences and effect of age at onset, and one with a focus on aggravating factors in the IBD patient such as infectious agents, non-steroidal anti-inflammatory drugs, and pregnancy.




Clinical Pharmacology


Book Description

A thorough knowledge of pharmacological and therapeutic principles is vital if drugs are to be used safely and effectively for increasingly informed patients. Those who clearly understand how drugs get into the body, how they produce their effects, what happens to them in the body, and how evidence of their therapeutic effect is assessed, will choose drugs more skilfully, and use them more safely and successfully than those who do not. Now in a fully revised 11th edition, Clinical Pharmacology is essential reading for undergraduate medical students, junior doctors and anyone concerned with evidence-based drug therapy. Introductory first three sections cover general principle of clinical pharmacology; five subsequent sections cover drug treatment of disease organised by body system. Retains approachable style set by the original author, Professor Laurence. Emphasis throughout is on evidence-based and safe drug prescribing. Indian Advisory Board will ensure content reflects the needs of the devloping world.




Ulcerative Colitis


Book Description

Dr. Gary R. Lichtenstein, along with Dr. Ellen J. Scherl, have collaborated with over 60 experts from around the world to provide gastroenterologists and those in training with the necessary information to successfully manage the patient with ulcerative colitis. Organized into an easy-to-reference format this book threads theory into practice and provides gastroenterology professionals with the most comprehensive information available. The other side of inflammatory bowel disease is covered in Drs. Gary R. Lichtenstein and Ellen J. Scherl.s Crohn.s Disease: The Complete Guide to Medical Management. All gastroenterologists will find both books to be essential for future practice in the treatment and care of their patients with either Crohn.s disease or ulcerative colitis, as well as in the overall management of those with inflammatory bowel disease.