Indirect treatment comparisons guide

Indirect Treatment Comparisons Guide: Everything you need to know


What is an Indirect Treatment Comparison?  

An Indirect Treatment Comparison (ITC) can provide an estimate of the relative treatment effect of two products that have not been compared directly. Ideally, this will be carried out using a common comparator which acts as an anchor for each product to compare to, e.g., a drug or placebo.  

For example, if Product A has been compared to Product C in one trial and Product B has been compared to Product C in another, it is possible to indirectly compare Product A to Product B, as shown in Figure 1. 

Figure 1: Simplified representation of an indirect treatment comparison 

Graphic showcasing how treatment C can form a link between treatments A and B which have never been compared directly

Why conduct an Indirect Treatment Comparison?   

In order to make decisions regarding which products to reimburse or recommend for use, healthcare decision makers should compare all relevant interventions.  

However, there are several reasons why direct comparative evidence may not be available: E.g.,  

  • Manufacturers conduct trials which are required to support reimbursement across multiple countries and as a result it is not always possible to conduct a head-head trial when considering that the appropriate comparator can vary.  
  • The appropriate comparator can vary between countries. For example, sertraline is the treatment of choice for PTSD in Germany but not in Australia where it does not have marketing authorisation for this condition.  

In many instances, to carry out a head-head trial for each potential comparator would be economically unviable and hence, if the comparator used in trials is not appropriate for the country of interest, an ITC is needed enable comparisons to be made.  

What are the limitations? 

In order to carry out an ITC, it is key to ensure that the clinical trial data are broadly comparable between studies. This may involve assumptions (as the full dataset or information may not be available) which can lead to varying degrees of uncertainty. The impact of this uncertainty must be considered when making treatment decisions based on the results of an ITC.  

Some examples of the types of assumptions which are often needed to carry out an ITC are listed below: 

  • The assumption of homogeneity, for example that all studies use the same number of patients which all have similar baseline characteristics. If differences in patient characteristics exist, it will be necessary to determine whether any of these differences are likely to be modifiers of the relative treatment effect. 
  • The assumption of similarity (or transitivity), this is an extension of homogeneity and assumes that all trials are similar enough to enable a fair estimate of the treatment effect. For example, the methods used to measure trial outcomes are the same 

What do payers think of ITCs? 

The use of ITCs has increased rapidly in recent years.  

Methods for indirect comparison are now accepted by many health technology assessment agencies, including the National Institute for Health and Care Excellence (NICE) in the UK, the Canadian Agency for Drugs and Technologies in Health (CADTH), the Pharmaceutical Benefits Advisory Committee (PBAC) in Australia, and the Haute Autorité de Santé (HAS) in France.  

However, ITCs may not always be accepted when there is uncertainty in the similarity of the compared studies. For example, up to May 2019, the Institute for Quality and Efficiency in Health Care in Germany (iQWiG) did not accept 84% of ITCs, citing use of unadjusted comparisons and a lack of data to support the ITC. This demonstrates how even in markets which theoretically accept ITCs such as Germany, there is hesitancy from payers to accept this form of comparison. 

Therefore, when making treatment decisions based on an ITC, payers will consider whether the level of uncertainty in the results is acceptable. It is therefore imperative that ITCs are robust and technically accurate to avoid creating unnecessary levels of uncertainty. 

How can Remap Consulting support you? 

Remap Consulting have significant expertise and up-to-date knowledge to support you to select the right evidence to achieve your pricing, reimbursement, and market access objectives.  

Interested in training and expanding your employees HTA knowledge? Our health technology assessment training enables learners to understand the concept of how HTA may be used to determine the price, reimbursement and/or access of a new pharmaceutical product and provides insights into what pharma companies should do to optimize outcomes for their products.  

If you would like to get in touch and see how we can help, email, or call us today at: or +44 (0)1625 709775. 

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