Cancer pain assessment, classification and patient reported outcomes in the evaluation of treatment effect
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Pain is common in patients with cancer and it has a strong impact on quality of life. Despite the development of guidelines, cancer pain treatment is suboptimal. This is often due to lack of efficient, standardized and widely applied methods for assessing and classifying pain and analgesic outcomes. Within the overall purpose of improving pain management in cancer patients, this PhD project aims at enhancing evidence on the methodology of pain assessment, classification and treatment to be integrated into evidence based guidelines. Some domains included in the "Edmonton Classification System for Cancer Pain" (neuropathic pain, breakthrough pain and psychological distress) lack of standardization in the assessment methods. In an international multicenter cross-sectional study on 563 patients with cancer pain, patient reported outcome measures (PROMs) were tested against physician clinical evaluation. Results showed that pain classification based on PROMs proved more effective than the one based of physician assessment. Neuropathic pain (NP) assessment methods vary according to local experience and between clinical settings. Based on the most recent definition and diagnostic criteria for NP, a Delphi survey among 29 international pain experts was conducted. Consensus was achieved on the relevance and on the adaptation of the proposed criteria in cancer patients, as well as on the possibility to use PROMs of pain descriptors for NP screening. A clinical algorithm for a standardized diagnosis of cancer NP was then proposed based on the adapted criteria. There is a lack of consistency in the definitions and methods used for the measurement of analgesic response. Data from a multicentre observational longitudinal study on 1461 cancer patients with pain, were analyzed to compare different PROMs commonly used in clinics and research for the assessment of analgesic effect. Worst and average pain intensity in the previous 24 hours revealed the most responsive PROMs for the measurement of pain variation over time. Among different definitions of endpoint, “final pain intensity value” (respectively <5 and <4 for worst and average pain intensity) showed the best accuracy in predicting patient satisfaction with treatment. Controlled release oral oxycodone and morphine are both recommended as first choice opioids for the treatment of moderate to severe cancer pain. Present guidelines are based on studies suggesting clinical equivalence between the two drugs but also having significant limitations when addressing tolerability. A multicentre open-label randomized controlled trial, involving 187 cancer patients with pain, was designed to compare oxycodone and morphine with a tolerability primary outcome. Results from this study were inconclusive on both tolerability and efficacy outcomes. Also, a prestated subgroup analysis provided no evidence of heterogeneity of treatment tolerability across age and renal function subgroups. However, these data can significantly contribute to future metaanalyses and are relevant in designing future studies. This thesis consistently confirms that different methodological choices regarding cancer pain assessment, classification and outcome measurement, have a strong impact on results obtained in clinical research and are important in the interpretation of clinical outcomes in pain management. Consensus on and dissemination of methodological standards in cancer pain research and clinic are needed.