Towards a more patient-centric evaluation of new anti-cancer treatments: Combined Assessment of Quality Of Life and Survival (CAQOLS)
As we know, the evaluation of clinical benefits achieved with cancer drugs is a complex problem. It is well described in two recent reviews, a study that systematically synthesized and analyzed English, French, and Australian health technology assessments (HTAs) of all new cancer medicines licensed in the United States and Europe between 2003 and 2013 (1) and a more recent study of cancer drug submissions between 2015 and 2018 to the Canadian Agency for Drugs and Technologies in Health (CADTH) (2).
The first study shows that of the 53 drugs that were evaluated by at least 1 HTA agency, 22 (42%) improved QoL, 2 (4%) reduced QoL, 1 (2%) was associated with mixed evidence, and 28 (53%) did not demonstrate a difference in QoL relative to best alternative treatments – For the list of QoL scales used, see below – and that not all regulatory opinions were based on robust evidence. Of the 22 drugs that were deemed to improve QoL, evaluations for 17 were based on a review of empirical evidence, including data from validated QoL instruments but the QoL benefits associated with the remaining 5 drugs were based exclusively on testimony from patient representatives and clinical experts. The authors concluded that although innovation in the oncology drug market has contributed to improvements in therapy, the magnitude and dimension of clinical benefits vary widely, and there may be reasons to doubt that claims of efficacy reflect real-world effectiveness exactly.
The second study shows that manufacturers do not traditionally report on health-related quality of life data that are meaningful to patients, that gains in QALYs in most submissions are small and that cost effectiveness is often over $ 100,000 per QALY. More than half of submissions did not include original data on health-related quality of life, with most of them relying instead on evidence from previous studies.
These findings indicate that manufacturers have opportunities to facilitate clinical decision-making by reporting on health-related quality of life data that will influence reimbursement decisions.
Like the authors of the two studies mentioned above, we believe that reimbursement decisions could be facilitated by the systematic addition of health-related quality of life questionnaires / scales to complement a traditional measure of efficacy such as overall response rate.
A measure of QoL could be incorporated into a combined assessment of a cancer relevant QoL scale and survival. One such measure that combines toxicity and toxicity is Q-Twist (3). But other novel approaches can be developed and applied. We have a method to combine cancer QoL scales with mortality using a non-parametric statistical approach.
Though inclusion of these measures will not influence regulatory approval, it will greatly support pricing and reimbursement decisions.
1. Salas-Vega et al. JAMA Oncol. 2017;3(3):382-390. doi:10.1001/jamaoncol.2016.4166
2. Raymakers et al., July 3, 2019, Published online Month 00, 2019 in Wiley Online Library.doi: 10.1002/cncr.32455
3. Huang M. et al. Pharmacoeconomics 2019 Jan;37(1):105-116. doi:10.1007/s40273018-0752-0
Chief Medical Officer and Co-founder
Pharma industry veteran with 30+ years in large Pharma & in leading small biotechs, spearheading large initiatives and securing funding, psychiatry practice and research for 10+ years.