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Characteristics and interpretation of subgroup analyses based on tumour characteristics in randomised trials testing
Stefan Schandelmaier1,2, Andreas M Schmitt3, Amanda K Herbrand3
1Institute for Clinical Epidemiology and Biostatistics, Department of Clinical Research, University Hospital and University of Basel, Basel, Switzerland s.schandelmaier@gmail.com.
Background:
Target-specific anticancer drugs are under rapid development. Little is known, however, about the risk of administering target-specific drugs to patients who have tumours with molecular alterations or other characteristics that can make the drug ineffective or even harmful. An increasing number of randomised clinical trials (RCTs) investigating target-specific anticancer drugs include subgroup analyses based on tumour characteristics. Such subgroup analyses have the potential to be more credible and influential than subgroup analyses based on traditional factors such as sex or tumour stage. In addition, they may more frequently lead to qualitative subgroup effects, that is, show benefit in one but harm in another subgroup of patients (eg, if the tumour characteristic makes the drug ineffective or even enhance tumour growth). If so, subgroup analyses based on tumour characteristics would be highly relevant for patient safety. The aim of this study is to systematically assess the frequency and characteristics of subgroup analyses based on tumour characteristics, the frequency of qualitative subgroup effects, their credibility, and the interpretations that investigators and guidelines developers report.
Methods And Analysis:
We will perform a systematic survey of 433 RCTs testing the effect of target-specific anticancer drugs. Teams of methodologically trained investigators and oncologists will identify eligible studies, extract relevant data and assess the credibility of putative subgroup effects using a recently developed formal instrument. We will systematically assess how trial investigators interpret apparent subgroup effects based on tumour characteristics and the extent to which they influence subsequent practice guidelines. Our results will provide empirical data characterising an increasingly used type of subgroup analysis in cancer trials and its potential impact on precision medicine to predict benefit or harm.
Ethics And Dissemination:
Formal ethical approval is not required for this study. We will disseminate the findings in a peer-reviewed and open-access journal publication.
Insights
Subgroup analyses in cancer trials examining target-specific drugs are crucial for patient safety. This study assesses their frequency, credibility, and impact on precision medicine, revealing potential benefits and harms in specific patient subgroups.
Area of Science:
- Oncology
- Clinical Trials
- Pharmacogenomics
Background:
- Target-specific anticancer drugs are rapidly advancing.
- Risks of using these drugs in patients with specific tumor alterations are not well understood.
- Subgroup analyses in randomized clinical trials (RCTs) are increasingly used to evaluate treatment effects based on tumor characteristics.
Purpose of the Study:
- To systematically assess the frequency and characteristics of subgroup analyses based on tumor characteristics in RCTs of target-specific anticancer drugs.
- To evaluate the frequency and credibility of qualitative subgroup effects (benefit in one subgroup, harm in another).
- To examine how trial investigators and guideline developers interpret and utilize these subgroup findings for patient safety and precision medicine.
Main Methods:
- Systematic survey of 433 RCTs for target-specific anticancer drugs.
- Data extraction and credibility assessment of subgroup effects by trained investigators and oncologists.
- Analysis of how subgroup effects influence practice guidelines.
Main Results:
- Empirical data on the use and impact of tumor-characteristic-based subgroup analyses in cancer trials will be provided.
- Insights into the potential for these analyses to predict benefit or harm in specific patient populations will be gained.
- The influence of these analyses on clinical practice and guidelines will be characterized.
Conclusions:
- Subgroup analyses based on tumor characteristics are vital for patient safety in the era of precision medicine.
- Understanding their credibility and interpretation is key to optimizing the use of target-specific anticancer drugs.
- This research will inform clinical practice and guideline development for personalized cancer therapy.
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