Understanding the barriers to, and facilitators of, ovarian toxicity assessment in breast cancer clinical trials

Background: Detailed toxicity data are routinely collected in breast cancer (BC) clinical trials. However, ovarian toxicity is infrequently assessed, despite the adverse impacts on fertility and long-term health from treatmentinduced ovarian insufficiency. Objectives: To determine the barriers to and facilitators of ovarian toxicity assessment in BC trials of anti-cancer drugs. Methods: Semi-structured interviews were conducted with purposively selected stakeholders from multiple countries involved in BC clinical trials (clinicians, consumers, pharmaceutical company representatives, members of drug-regulatory agencies). Participants were asked to describe the perceived benefits and barriers to evaluating ovarian toxicity. Interviews were transcribed verbatim, coded in NVivo software and analysed using inductive thematic analysis. Results: Saturation of the main themes was reached and the final sample size included 25 participants from 14 countries (9 clinicians, 7 consumers, 5 members of regulatory agencies, 4 pharmaceutical company representatives); half were female. The main reported barrier to ovarian toxicity assessment was that the issue was rarely considered. Reasons included that these data are less important than survival data and are not required for regulatory approval. Overall, most participants believed evaluating the impact of BC treatments on ovarian function is valuable. Suggested strategies to increase ovarian toxicity assessment were to include it in clinical trial design guidelines and stakeholder advocacy. Conclusion: Lack of consideration about measuring ovarian toxicity in BC clinical trials that include premenopausal women suggest that guidelines and stronger advocacy from stakeholders, including regulators, would facilitate its more frequent inclusion in future trials, allowing women to make better informed treatment decisions.

Automated summary

This study aimed to determine the barriers to and facilitators of ovarian toxicity assessment in breast cancer clinical trials. Through semi-structured interviews with stakeholders from multiple countries, the main barrier identified was the lack of consideration. However, most participants believed that evaluating the impact of breast cancer treatments on ovarian function is valuable. Suggested strategies to increase ovarian toxicity assessment included including it in clinical trial design guidelines and stakeholder advocacy.