Clinical trials: a summary

Archive of Oncology, 2003

Revista Española de Cardiología (English Edition), 2006

American Journal of Ophthalmology, 2009

Purpose-To review the development of clinical trials and demonstrate their value beyond the assessment of the treatment effect. Design-Retrospective literature review Methods-Retrospective literature review Results-There has been a rapid increase in the number of clinical trials in ophthalmology as assessed by the number of ophthalmic publications and the number of ongoing National Eye Institute (NEI) sponsored clinical trials over the last four decades. The public health significance of the results of these NEI clinical trials goes beyond the demonstration of treatment effects and side effects. From these trials we learn about the clinical course and risk factors of disease allowing us to better determine who and when to treat. Furthermore, the collaboration of investigators, as they develop and carry out protocols, facilitates incorporation of new ideas into the practice of medicine. Conclusions-The practice of medicine is increasingly dependent on the results of carefully designed clinical trials. The determination as to whether a new treatment is safe and effective is important, but the additional information we can obtain regarding natural history, risk factors, and patient satisfaction adds immeasurably to our ability to care for our patients. Imagine what it would be like to be told that you have been selected by the American Academy of Ophthalmology and the American Journal of Ophthalmology, both founded by Dr. Edward Jackson, to be 65 th Edward Jackson Memorial lecturer. To be listed among this group of ophthalmologists, from whom we have all have learned so much, and to be associated with Dr. Edward Jackson and his extraordinary contributions to ophthalmology is a special honor. Although Dr. Jackson was not particularly involved in clinical trials during his career, he was devoted to improving the standards of patient care and I have no doubt that he would think it most appropriate to discuss the impact that clinical trials have made to ophthalmology and patient care in his named lecture. Clinical trials have slowly evolved to their current status as the "gold standard' by which we decide if treatments are safe and effective. However, we have an opportunity to learn far more than this from each clinical trial. The dedicated efforts of clinicians and clinic coordinators, as they carefully collect long-term data on the patients in the clinical trial, provide a wealth of information that assists us in the daily care of our patients. We learn about the clinical course

Journal of the Royal Society of Medicine, 2007

Objective Scientific and ethical justification for new clinical trials requires them to have been designed in the light of scientifically defensible assessments of relevant previous research. Reliable interpretation of the results of new clinical trials entails setting them in the context of updates of the reviews upon which they were deemed scientifically and ethically justifiable. We have shown previously that most reports of randomized trials published in five general medical journals in May 1997 and in May 2001 failed to set their results in the context of the findings from similar research. In the current study, we assess whether there had been progress in this respect in 2005 and also investigate the extent to which reports begin by referring to systematic reviews providing the justification for the new research reported. Design Assessment of the Introduction and Discussion sections in all reports of randomized trials published during May 2005 in five general medical journals. Setting Reports of randomized trials in five general medical journals.

Spine, 2006

Study Design. A critical appraisal of the literature. Objectives. To increase awareness of the importance of applicability and clinical relevance of the results of randomized controlled trials (RCTs) in the field of spinal disorders by formulating a list of items for assessment of applicability and clinical relevance of results of RCTs. Summary of Background Data. In systematic reviews of randomized controlled trials (RCTs), critical appraisal of methodologic quality is considered important. Less attention has been paid to the assessment of the applicability and the clinical relevance of the results. Methods. RCTs in an update of the Cochrane review on exercise therapy for low back pain were used. Most of the trials did not score positively on the five Cochrane Back Review Group basic items describing patients: intervention and setting, outcome, effect size, and benefits related to adverse effects. Item 1 was met by 88% of the trials, but item 2 only by 51%, item 3 by 67%, item 4 by 35%, and item 5 by 0%. Subsequently, a more comprehensive list of items for the assessment of applicability and clinical relevance of results of RCTs was developed. These criteria were pilot tested on the RCTs. After pilot testing and a subsequent consensus meeting, the list of items was drafted and circulated among the members of the Editorial Board of the Cochrane Back Review Group. Changes were made in response to comments. Results. The final list consists of 40 items. The items are ordered on two headings: Does the report enable the assessment of applicability? Are the study results clinically relevant? We present examples of informative and noninformative reporting of RCTs in order to illustrate how information on applicability and clinical relevance of results can be assessed. Conclusions. Authors of RCTs should adequately report on items that are essential to assess the applicability and clinical relevance of results. The presented list of items may help clinicians reading RCTs and authors of systematic reviews to draw more balanced conclusions on applicability and clinical relevance of results.

British Journal of Medicine and Medical Research, 2013

The hierarchy of evidence-based medicine determines the inferential powers of different clinical research designs. We want to address the difficult question if observational evidence under some circumstances can validate intervention effects. Methodology: Assessment of previous argumentation aiming at a clear conclusion for future decision-making. Results: We present five arguments demonstrating the fundamental need of randomized clinical trials to sufficiently validate intervention effects. Furthermore, we argue that hindrances to the conduct of randomized clinical trials can be lessened through education, collaboration, infrastructure, and other measures. Our arguments validate why the randomized clinical trial should and must be the study design evaluating interventions. By choosing the randomized clinical trial as the primary study design, effective preventive, prognostic, diagnostic, and therapeutic interventions will reach more patients earlier.

Elsevier eBooks, 2003

2007

The purpose of this paper is to discuss whether the randomized clinical trial (RCT) is indeed the gold standard among epidemiological studies. This paper illustrates to what extent different study designs may contribute to the answer of the following therapeutic research question based on a study of Wanner et al.: 'Is the use of a statin associated to less cardiac mortality in patients with type 2 diabetes mellitus who receive hemodialysis?' If a therapeutic study is feasible, like the research question of the clinical example, the RCT is almost unbeatable: the problems that may occur in the other study designs do not exist or to a lesser extent using an RCT. The main advantage of an RCT is that the randomization procedure helps to prevent selection bias by the clinician by breaking the link between the clinician's therapy prescription and the patient's prognosis. Within observational studies, however, selection by the clinician may occur, and, even after adjustment for potential confounders in the statistical analysis, it may not be possible to make a fair comparison between the groups. Usually, results from observational studies are needed to come to a hypothesis that can subsequently be tested within an RCT. Moreover, observational data are most often more useful than RCTs for non-therapeutic studies.

Trials

There are many reasons why the majority of clinical trials fail or have limited applicability to patient care. These include restrictive entry criteria, short duration studies, unrecognized adverse drug effects, and reporting of therapy assignment preferential to actual use. Frequently, experimental animal models are used sparingly and do not accurately simulate human disease. We suggest two approaches to improve the conduct, increase the success, and applicability of clinical trials. Studies can apply dosing of the investigational therapeutics and outcomes, determined from animal models that more closely simulate human disease. More extensive identification of known and potential risk factors and confounding issues, gleaned from recently organized “big data,” should be utilized to create models for trials. The risk factors in each model are then accounted for and managed during each study.