{"id":383106,"date":"2024-07-26T07:20:35","date_gmt":"2024-07-26T05:20:35","guid":{"rendered":"https:\/\/medizinonline.com\/?p=383106"},"modified":"2024-07-26T07:20:49","modified_gmt":"2024-07-26T05:20:49","slug":"differences-in-design-and-their-significance-for-interpretation","status":"publish","type":"post","link":"https:\/\/medizinonline.com\/en\/differences-in-design-and-their-significance-for-interpretation\/","title":{"rendered":"Differences in design and their significance for interpretation"},"content":{"rendered":"\n

What study phases does a new active substance go through before it reaches clinical practice?\nWhat differences are there in the designs of clinical trials?\nWhich aspects are important for interpreting results?\nIn this CME training article, the development of clinical trial designs in inflammatory bowel disease (IBD) will be shown and it will be explained how endpoints change from clinical measurements to patient-based data and how mixed endpoints are composed of endoscopic and patient-based assessments. <\/strong><\/p>\n\n\n\n

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What study phases does a new active substance go through before it reaches clinical practice?\nWhat are the differences in clinical trial designs?\nWhich aspects are important for interpreting results?\nIn this CME training article, the development of clinical trial designs in inflammatory bowel disease (IBD) is shown and it is explained how endpoints change from clinical measurements to patient-based data and how mixed endpoints are composed of endoscopic and patient-based assessments [1]. <\/p>\n\n

Different phases of clinical studies<\/h3>\n\n

There are different phases of clinical trials.\nThe first phase – phase 1 – takes place with smaller groups of usually less than 80 participants [2].\nSometimes also with healthy volunteers, on whom the active substances are tested, especially with regard to safety and dosage.\nThe aim is to evaluate dosage, form of administration and safety [3,4]. <\/p>\n\n

Once these factors have been tested, phases 2a and 2b follow.\nIn phase 2a, the proof of concept is typically tested, phase 2b evaluates the efficacy\/safety and determines the dosage and procedure for phase 3 trials [5].\nIn the field of inflammatory bowel disease, phase 2b is particularly important – the aim here is to understand exactly how high the dosage should be and how it should be administered in order to achieve the best efficacy. <\/p>\n\n

Phase 3 usually involves between 500 and 1000 patients.\nThe aim of this phase is to determine whether safety and efficacy are confirmed and whether they are relevant.\nPhase 3 trials are subject to strict statistical procedures and rigorous designs that can lead to approval.\nThey are usually randomized and blinded to placebo [6].\nIt is important to have the possibility to compare: either with a placebo or another active substance.\nWhen interpreting the results, it is also important to check whether the study had a strict, predetermined statistical analysis plan [6]. <\/p>\n\n

The significance of the study is influenced by endpoints defined at the beginning: In IBD, clinical remission and clinical response are usually primary endpoints.\nActive comparators selected as controls determine the significance of the results [7,8]. <\/p>\n\n

Once the active substance has been approved and is on the market, observational phase 4 follows, in which significantly more patients (>100,000) can be included and observed.\nThe endpoints are less strictly defined here, but the follow-up period is longer.\nIn this phase, the focus is primarily on further safety aspects of the active substance, which, due to their rarity, only arise if a correspondingly large number of patients are available in the real-world setting. <\/p>\n\n

Categories of clinical trial designs and their limitations<\/h3>\n\n

Placebo-controlled studies<\/em> are not always uncontroversial, as the use of a placebo in many clinical studies appears ethically questionable.\nIn IBD, placebos are therefore used for a short period (8-12 weeks induction) and with a small control arm (2:2:1).\nIf the patient shows no response after this time, they can also receive the verum later.\nControl groups are also developed for numerous studies (umbrella\/platform studies). <\/p>\n\n

Then you have to find the right comparator <\/em>: In general, the standard of care (SOC) or the choice of standard therapies by the treating physicians can determine the credibility of the results [8,9].\nWithout appropriate comparators, studies may not be able to demonstrate whether an investigational therapy is superior to prevailing practice and\/or leads to bias [10]. <\/p>\n\n

Active comparators may not be suitable, depending on, among other things:<\/p>\n\n