YHEC offers a range of services to inform the development and conduct of indirect and mixed treatment comparisons (ITC and MTC).
Working in partnership
YHEC delivers systematic review, meta-analyses, indirect and mixed treatment comparisons and HTA submissions, working in close collaboration with our partners at Quantics . YHEC provides expertise in systematic reviews, assessing the feasibility of indirect comparisons and HTA submissions. Quantics provides statistical expertise in the conduct of meta-analysis and indirect and mixed treatment comparisons.
What are Indirect and Mixed Treatment Comparisons?
Indirect and mixed treatment comparisons (network meta-analyses, NMA) are statistical tools for assessing, for example, the comparative efficacy and safety of interventions when:
- There is no direct evidence between the interventions of interest,
- There is insufficient direct evidence or
- There are more than two interventions that need to be compared.
NMA methods are developing quickly and are already being widely used in health care to inform decisions which require an understanding of the comparative effectiveness of different treatments, devices and diagnostic techniques.
When to conduct an NMA?
- NMA are now accepted as part of health technology assessments in many countries including England (NICE), France (Haute Autorité de Santé), Canada (Canadian Agency for Drugs and Technologies in Health) and Australia (Pharmaceutical Benefits Advisory Committee).,
Inform an economic model
- At YHEC, we have experience of building and adapting economic models for hundreds of health care technologies. The outputs of NMA can be used to inform the model inputs. ,
Produce a publication
- We can support you to carry out a systematic review and conduct NMA in line with the ISPOR and PRISMA NMA reporting guidelines.,
Inform future trials
- We can help you interpret the results of your trial within the context of comparator trials, or to assess the landscape of comparator trials and inform plans for future clinical trials.,
How can we help you?
As with a standard pairwise meta-analysis, the validity of a NMA depends on:
- The adequacy of the evidence base;
- The similarity of the trials.
These issues underpin the focus of the systematic review and feasibility assessment of whether an NMA is possible.
We can help you to define your research question and to develop a review protocol to ensure that the review will help you to answer those questions. We can undertake extensive literature searches to ensure all studies relevant to the review question and the NMA are identified. Once identified, we can assess the risk of bias of the individual trials and extract the relevant data required to assess the feasibility of a NMA and to inform any subsequent statistical analyses.
A key assumption when conducting a NMA is that the trials in the network do not differ in any characteristics that may impact the treatment effect (i,e the difference in response between two treatments).
We consider the similarity of key characteristics of the trials in relation to:
- Trial design/methodology
- Patient characteristics at baseline
- Treatments received
- Outcomes reported
We also consider the availability of outcome data for each outcome of interest in each of the trials. Based on the data available, we can then determine whether a connected network can be made for each outcome of interest.
We can conduct network meta-analyses, through our partnership with Quantics, to compare the efficacy, safety or tolerability of two or more treatments. We can help with simple and complex NMA as well as more complex network meta-regressions and we can advise you on the best methods to use for the data available.
Critiques of published NMAs
We have extensive experience of assessing the quality of both peer-reviewed publications and health technology assessment submissions. In conjunction with Quantics, we can appraise all aspects of systematic reviews and NMA.
The quality of published NMAs is highly variable. Quantics and YHEC can help you to answer questions such as:
- Are the search terms and search resources appropriate to ensure that as many relevant trials as possible will have been identified?
- Have the data been correctly extracted from the publications?
- Has the similarity of the trials been considered before combining them in a network?
- Have the most appropriate statistical methods been used to conduct the NMA?
- Are the published results reproducible?
- Have the results been correctly interpreted?
To learn more about our services and experience please see the Indirect Treatment Comparisons website.
Examples of Recent Publications
- Malcolm WA, Hodgson R, Glanville J, Barata T, Fleetwood K. Indirect Treatment Comparison of Interventions for Neovascular (Wet) Age-Related Macular Degeneration (Wet AMD). ISPOR 2015.
- Bachelot T, McCool R, Duffy S, Glanville J, Varley D, Fleetwood K, Zhang J, Jerusalem G. Comparative efficacy of everolimus plus exemestane versus fulvestrant for hormone-receptor-positive advanced breast cancer following progression/recurrence after endocrine therapy: a network meta-analysis. Breast Cancer Res Treat 2014 Jan;143(1):125-33. [Epub ahead of print]
- Bachelot T, Jerusalem G, Cikalo M, McCool R, King S, Duffy S, et al. Comparative efficacy of everolimus versus fulvestrant for hormone-receptor–positive (HR+) advanced breast cancer (ABC) following progression/recurrence after first-line treatment: A network meta-analysis. J Clin Oncol. 2013;31(Suppl):e11602.(Published in conjunction with the 2013 ASCO Annual Meeting).
- Chandiwana D, Vieira J, Bains M, Heaton V, Zhang J, Glanville J, McCool R, Fleetwood K. An indirect treatment comparison of the efficacy of Everolimus (Afinitor®) and Fulvestrant for the treatment of hormone receptor positive (HR+) HER2 negative (HER2-) advanced or metastatic breast cancer. ISPOR Poster 2013.
- Martyn-St.James M, Glanville J, McCool R, Duffy S, Cooper J, Hugel P, Lane P W. The efficacy and safety of retigabine and other adjunctive treatments for refractory partial epilepsy a systematic review and indirect comparison. Seizure 2012; 21(9):665-678.