A comparator is the treatment with which an investigational medicinal product is compared in a controlled clinical trial. It can be an authorized medicinal product, an active standard treatment or, in appropriate situations, a placebo. Its selection determines what conclusion about the treatment effect is possible and influences the ethical as well as the statistical justification of the study design.<\/p>\n
A control group should show what results would be expected in comparable persons without the investigational treatment or under another treatment. ICH E10 emphasizes that the choice of the control group influences the inferable conclusions, ethical acceptability, minimization of bias, choice of endpoint and regulatory acceptance. In a randomized parallel-group study, the groups receive the treatments to be compared according to the pre-defined allocation procedure.<\/p>\n
An active comparator is particularly relevant when an effective therapy is available and the new treatment is to be contextualized within the care environment. Depending on the objective, the study can investigate superiority, non-inferiority or another pre-defined treatment effect. The comparator treatment must thereby be precisely specified for population, indication, dose, concomitant therapy and time period. Only in this way is it clear to what the estimated difference refers.<\/p>\n
The selection is justified scientifically and ethically in the protocol. Decisive factors include the available evidence on efficacy, the therapeutic standard, the expected care of the target population and the conclusion that the design is intended to support. In a non-inferiority study, the active control requires in particular a comprehensible historical proof of efficacy; otherwise, the non-inferiority margin cannot be credibly derived.<\/p>\n
Operationally, origin, specification, storage, labelling, distribution and traceability of the comparator must be planned. Different pharmaceutical forms can complicate blinding and make an appropriate masking or a double-dummy design necessary. Changes to product, batch or supply route must not unnoticeably impair comparability. The relevant requirements for manufacturing and labelling of investigational medicinal products as well as the protocol regulate the documentation required for this.<\/p>\n
With cross-border procurement, availability, local packaging, shelf life and release status must also be clarified in good time. The supply of the study centers must lead neither to interruptions in the comparator arm nor to avoidable deviations from the intended treatment. Quality risks are controlled by a comprehensible distribution of responsibilities between sponsor, suppliers, depot and study center.<\/p>\n
Placebo is a possible type of comparator treatment, but not to be equated with the umbrella term comparator. A placebo contains no pharmacologically active ingredient for the investigated indication and can support a comparison to the absence of the specific effect. Whether its use is justifiable depends, among other things, on available effective therapy, disease risk, study duration and intended protective measures. The comparator can equally be an active therapy.<\/p>\n
The investigational medicinal product, also IMP, is the treatment investigated in a clinical trial; it can be the subject of the proof of efficacy or safety. The comparator, on the other hand, refers to the reference treatment in the comparator arm. Under the regulatory definitions, various medicinal products used in the study can be investigational medicinal products, including a comparator. For the methodological description, however, their role in the comparison remains to be clearly separated.<\/p>\n
This conceptual separation also prevents the scientific function from being confused with the pharmaceutical classification. For the analysis, what matters is which treatment conditions are compared; for manufacturing, labelling and accountability, the respective regulatory requirements for the medicinal products used in the trial apply.<\/p>\n
An unsuitable comparator treatment can fundamentally limit the interpretability of a study. In the study design, treatment regimen, background therapy, rescue medication and handling of therapy changes must therefore align with the clinical question and the estimand. In multinational studies, market availability, local supply and a consistent supply of study centers are added as additional risks.<\/p>\n
Full-service CROs such as Mediconomics support the methodological justification of the comparator treatment, the coordination of protocol and statistical analysis plan as well as procurement and supply planning. Concrete services encompass the documentation of the product specification, the coordination of labelling and blinding, monitoring of the medicinal product processes and the biostatistical evaluation of the comparison strategy.<\/p>\n
Must a comparator always be an authorized medicinal product?<\/strong><\/p>\n No. Depending on the research question, the comparator treatment can also be placebo, no treatment, a different dose or a defined standard of care. The choice must support the intended conclusion and the ethical requirements.<\/p>\n Why is the origin of the active comparator important?<\/strong><\/p>\n Origin and specification are relevant for quality, traceability and comparability. Different formulations, storage conditions or supply chains can influence the practical conduct and possibly the blinding.<\/p>\n Is standard of care always a single comparator?<\/strong><\/p>\n No. Standard of care can comprise a medicinal product, a combination, a sequence of treatments or even non-pharmacological measures. The protocol must describe it sufficiently precisely.<\/p>\n A comparator is the treatment with which an investigational medicinal product is compared in a controlled clinical trial. It can be an authorized medicinal product, an active standard treatment or, in appropriate situations, a placebo. Its selection determines what conclusion about the treatment effect is possible and influences the ethical as well as the statistical […]<\/p>\n","protected":false},"author":10,"featured_media":0,"parent":0,"template":"","meta":{"_acf_changed":false,"site-sidebar-layout":"default","site-content-layout":"","ast-site-content-layout":"default","site-content-style":"default","site-sidebar-style":"default","ast-global-header-display":"","ast-banner-title-visibility":"","ast-main-header-display":"","ast-hfb-above-header-display":"","ast-hfb-below-header-display":"","ast-hfb-mobile-header-display":"","site-post-title":"","ast-breadcrumbs-content":"","ast-featured-img":"","footer-sml-layout":"","ast-disable-related-posts":"","theme-transparent-header-meta":"","adv-header-id-meta":"","stick-header-meta":"","header-above-stick-meta":"","header-main-stick-meta":"","header-below-stick-meta":"","astra-migrate-meta-layouts":"set","ast-page-background-enabled":"default","ast-page-background-meta":{"desktop":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"tablet":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"mobile":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""}},"ast-content-background-meta":{"desktop":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"tablet":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"mobile":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""}},"footnotes":""},"glossary-cat":[],"class_list":["post-7010","glossary","type-glossary","status-publish","hentry"],"acf":[],"related_terms":"","external_url":"","internal_reference_id":"","_links":{"self":[{"href":"https:\/\/mediconomics.com\/en\/wp-json\/wp\/v2\/glossary\/7010","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/mediconomics.com\/en\/wp-json\/wp\/v2\/glossary"}],"about":[{"href":"https:\/\/mediconomics.com\/en\/wp-json\/wp\/v2\/types\/glossary"}],"author":[{"embeddable":true,"href":"https:\/\/mediconomics.com\/en\/wp-json\/wp\/v2\/users\/10"}],"version-history":[{"count":2,"href":"https:\/\/mediconomics.com\/en\/wp-json\/wp\/v2\/glossary\/7010\/revisions"}],"predecessor-version":[{"id":7422,"href":"https:\/\/mediconomics.com\/en\/wp-json\/wp\/v2\/glossary\/7010\/revisions\/7422"}],"wp:attachment":[{"href":"https:\/\/mediconomics.com\/en\/wp-json\/wp\/v2\/media?parent=7010"}],"wp:term":[{"taxonomy":"glossary-cat","embeddable":true,"href":"https:\/\/mediconomics.com\/en\/wp-json\/wp\/v2\/glossary-cat?post=7010"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}Regulatory references<\/h2>\n
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