Basic↦Statistic Methodology↦Research Question↦Placebo and Comparator
What is it? Why is it important?
A Placebo or Comparator is used as a control in interventional studies.
A placebo is an inactive:
- Harmless substance (e.g. sugar pill, saline/water solution). Placebo studies are blinded studies, where study participants do not know if they belong to the placebo or the intervention group
A comparator is an active:
- Therapeutic product (e.g. medicinal product or medical device) expected to be similar in indication and formulation to the intervention. A comparator usually represents current best practice, against which the intervention is being tested (i.e. these studies can also be blinded)
The aim of using a:
- Placebo is to confirm that any observed safety or efficacy differences between the placebo and the intervention group can be attributed to the intervention (e.g. placebo has no effect)
- Comparator is to confirm a potential superiority, similarity, or inferiority effect of the interventional product
More
Placebo studies are either:
- Single-blinded: in these studies study participants are blinded to the treatment they receive. The study team does not inform the participant about his/her assigned treatment group (e.g. placebo or intervention)
- Double-blinded: in these studies both the participant, investigators (e.g. SP-INV, Site-INV), and the extended study team are blinded to the treatment allocation between placebo and intervention. An un-blinded study nurse is usually appointed to manage and hand out treatment products
The placebo effect: is the occurrence of an effect in the placebo group that mirrors the expected effect of the intervention group, despite not having been administered the therapeutic product. It is alleged that the placebo effect is tied to the expectation of a presumed expected effect triggered by the intervention
What do I need to do?
As a SP-INV, when planning a placebo/comparator study, ensure:
- The placebo product is manufactured in accordance with GMP, and undistinguishable from the interventional product (e.g. size, texture, viscosity, colour, etc.)
- Both placebo and the interventional product is coded and labelled in a manner that protects blinding (i.e. ensure labelling complies with regulatory requirements)
- Budgetary resources are guaranteed
Placebo/comparator studies can be challenging requiring diligent planning and additional resources (e.g. production of the placebo product, handling and management of the placebo/comparator and the interventional product, expertise of study staff, additional processes to ensure blinding)
In guarantee that placebo/comparator groups are comparable with the treatment group:
- Plan for treatment and placebo/comparator allocation to be randomized
- Define processes that ensure that the research team remains blinded
- For the data analysis ensure the statistician is blinded to the treatment allocation (i.e. a statistician should be contacted early during study planning)
Where can I get help?
Your local CTU↧ can support you with experienced staff regarding this topic
Basel, Departement Klinische Forschung, CTU, dkf.unibas.ch
Lugano, Clinical Trials Unit, CTU-EOC, www.ctueoc.ch
Bern, Clinical Trials Unit, CTU, www.ctu.unibe.ch
Geneva, Clinical Research Center, CRC, crc.hug.ch
Lausanne, Clinical Research Center, CRC, www.chuv.ch
St. Gallen, Clinical Trials Unit, CTU, www.kssg.ch
Zürich, Clinical Trials Center, CTC, www.usz.ch
References
ICH GCP E6(R2) – see in particular guidelines
- 1.14. Comparator (Product)
- 5.13. Manufacturing, packaging, labelling, and coding investigational product(s)
ISO 14155:2020 Medical device (access liable to cost) – see in particular section
- 3.12 Comparator definition
- 3.15 Control group
- 3.50 Subject
Swiss Law
HRA – see in particular article
- Art. 13 Placebo