Overall Treatment Utility
In Oncology clinical research, Overall Treatment Utility (OTU) is a composite clinical outcome measure designed to quantify the effect of palliative treatments on individuals with a diagnosis of advanced or incurable cancer.
OTU attempts to capture the balance of benefits and harms from cancer treatments. It combines clinical and radiological response, toxicity, adverse events, quality of life and patient-reported acceptability of treatment.
As a concept, the measure may be regarded as asking the treating clinician: “With the benefit of hindsight, are you glad you gave this treatment?” and asking the patient: “With the benefit of hindsight, are you glad you received it?.”
Overall Treatment Utility may be considered a more patient centred intermediate endpoint as a response to criticism leveled at the increasing reliance on surrogate endpoints by drug regulators. The inclusion of Overall Treatment Utility as a pre-defined endpoint has now been seen in a variety of clinical trials in the United Kingdom, including FOCUS2, 321GO, GO2 and the ROSELEE study.
It is common to report OTU after 9 or 12 weeks of treatment.
For more information about OTU or if you are considering using it in a study please get in touch.
As an outcome measure, Overall Treatment Utility has been validated as a better predictor of both Progression Free Survival and survival rate compared with tumor response alone as measured by the gold standard Response Evaluation Criteria in Solid Tumors (RECIST).
Overall Treatment Utility was first developed within within the FOCUS2 clinical trial in elderly patients treated with chemotherapy for advanced colorectal cancer. A variety of baseline clinical characteristics were shown to predict for benefit or harm as measured by Overall Treatment Utility using an ordered logit model. Validation and further development took place in the context of the 321GO clinical trial that looked at chemotherapy intensity in the palliative treatment of patients with advanced gastric and oesophageal cancer.
As a clinical outcome measure, Overall Treatment Utility needs further development and validation. If you would like to help please get in touch.
Based on a work at https://blogs.ed.ac.uk/canceroutcomes/. Contact Peter Hall for more info.
Presenting OTU results
To score Overall Treatment Utility, a patient is assessed at a pre-defined time-point from commencement of treatment. Overall Treatment Utility is scored as good, intermediate or poor, corresponding to “yes”, “uncertain” or “no” replies to these questions.
Scoring uses the following criteria:
1. Clinical benefit?
- Score 1 if all of:
- No evidence of radiological progression
- No cancer-related clinical deterioration , as assessed by treating physician
- No deterioration in patient reported outcomes
- Score 0 if any of:
- Radiological progression
- Clinical deterioration, as assessed by treating consultant
- Deterioration in patient reported quality of life
2. Tolerable and acceptable?
- Score 1 if all of the following:
- No Serious Adverse Reaction (SAR) or Suspected Unexpected Serious Adverse Reaction (SUSAR) attributed to treatment
- Patient response to question “How much has your treatment interfered with your normal daily activities?” is not “Very much” or “quite a bit”
- Patient response to question (“How worthwhile do you think your treatment has been?”) is not “Not at all”
- Score 0 if any of the following:
- SAR or SUSAR attributed to treatment
- Patient response to question “How much has your treatment interfered with your normal daily activities?”) is “Very much” or “quite a bit”
- Patient response to question “How worthwhile do you think your treatment has been?” is “Not at all”
Patient is alive and scores 2
Patient is alive and scores 1
Patient is alive and scores 0, or patient is dead
- Knopf K, Baum M, Shimp WS, Bennett CL, Faith D, Fishman ML, Hrushesky WJ (30 December 2016). “Interpretation of surrogate endpoints in the era of the 21st Century Cures Act”. British Medical Journal. 355: i6286. doi:10.1136/bmj.i6286. PMID 28039123.
- Handforth C, Hall PS, Marshall HC, Collinson M, Jones M, Seymour MT (2013). “Overall treatment utility: a novel outcome measure reflecting the balance of benefits and harms from cancer therapy”. European Journal of Cancer. 49 (S2): 346.
- Seymour, M; Thompson, L; Wasan, H (2011). “Chemotherapy options in elderly and frail patients with metastatic colorectal cancer (MRC FOCUS2): an open-label, randomised factorial trial”. The Lancet. 21 (377): 1749–59.
- Hall PS, Lord SR, Collinson M, Marshall H, Jones M, Lowe C, Howard H, Swinson D, Velikova G, Anthoney A, Roy R, Seymour M (2017). “A randomised phase II trial and feasibility study of palliative chemotherapy in frail or elderly patients with advanced gastroesophageal cancer (321GO)”. British Journal of Cancer. 116 (4): 472–478. doi:10.1038/bjc.2016.442. PMC 5318975. PMID 28095397.
- “The GO2 trial: Alternative chemotherapy for frail or elderly patients with advanced gastric or oesophageal cancer”. ASCO abstract: http://abstracts.asco.org/239/AbstView_239_259067.html