ABSTRACT
Title
Inadequate cancer pain management in clinical trials
Authors
V. Maggini1, E. Lucenteforte1, R. Maione2, V. Fabbroni3, C. Tomino2, A. Mugelli1,4
1Dept. of Preclinical and Clinical Pharmacology “M. Aiazzi Mancini”, Centre for Molecular Medicine (CIMMBA), University of Florence, Florence, Italy
2Research and Clinical Trial, Italian Medicines Agency, Rome, Italy
3SC Medical Oncology, Santa Maria Anunziata Hospital, Bagno a Ripoli, Florence,
Italy
4Tuscan Regional Centre of Pharmacovigilance, Florence, Italy
1Dept. of Preclinical and Clinical Pharmacology “M. Aiazzi Mancini”, Centre for Molecular Medicine (CIMMBA), University of Florence, Florence, Italy
2Research and Clinical Trial, Italian Medicines Agency, Rome, Italy
3SC Medical Oncology, Santa Maria Anunziata Hospital, Bagno a Ripoli, Florence,
Italy
4Tuscan Regional Centre of Pharmacovigilance, Florence, Italy
Abstract
Cancer-related pain is one of the most feared symptoms and at least 70% of patients experience pain sufficiently severe to require chronic opioid treatment (Plante, 2010). Despite implementation of WHO guidelines (1998), undertreatment of cancer-related pain persisted in various clinical settings (Cleeland, 1994; Kart, 1997; Urban, 2010) with a prevalence still very high (Apolone, 2009). In order to improve the situation, a complete assessment of pain (type, measurement, treatment, relief degree) to be reported in all clinical records is become compulsory in Italy (Law no. 38, 2010).
Present study aimed to investigate if/how pain assessment was reported in all oncology protocols approved by Italian ethical committees and recorded in 2008 in a database of the National Monitoring Centre of Clinical Trial of the Italian Medicines Agency (AIFA).
Among protocols involving cancer diseases likely associated with pain - selected by an expert oncologist -, those including pain treatment and measurement, were identified by searching the texts for the following themes: “pain*” combined (using the Boolean operator “and”) “supportive care” or “pain management” or “pain treatment” or “analgesic*” or “morphin*” or “opioid*” or “opiate”. In a second search the themes “vas” or “nrs” or “vns” or “vrs*” or “vds*” or “quality of life” were used. Protocols including these themes were then independently reviewed by two investigators. To validate the search strategy, 10% of excluded protocols were randomly selected for further review.
One hundred and forty-three protocols were reviewed, 58 (40.6%) were investigator initiated studies, the others were promoted and sponsored by drug companies. Seventy-nine studies (55.2%) concerned phase II clinical trials, 29 (20.3%) were on lung cancer, 20 (14.0%) on breast cancer, and 16 (11.2%) on colorectal cancer. In 52 (36.4%) protocols pain treatment was mentioned, 35 (67.3%) included analgesics generic use, 11 (21.2%) included opiates use - but only 2 of these 11 reported specific guidelines -, and 6 (11.5%) included pain treatment without mentioning any drugs. Moreover, in 26 (18.2%) protocols supportive care was mentioned but not specifying pain. None of the protocols took into account the breakthrough cancer pain. As concern pain measure, 53 (37.1%) protocols considered pain measurement, of these 9 (17.0%) adopted a specific questionnaire focused on pain (Brief Pain Inventory, McGill Pain, Present Pain Intensity Questionnaires) and 44 (83.0%) adopted questionnaire about quality of life (EORTC, QLQ, FACT, EQ5D Questionnaires) including at least a specific item on pain. Twenty-five (17.5%) protocols included both pain treatment and measurement.
Our data indicates that in 2008 pain assessment and treatment were still not reported as it should have been in oncology clinical study protocols. The present analysis should be replicated including all oncology protocols recorded after the approval of the law 38 in 2010. Finally, ethical committees should pay close attention on pain therapy when evaluating oncology clinical study protocols.
Apolone et al. (2009). Br J Cancer 100, 1566-1574.
Cleeland et al. (1994). N Engl J Med. 330, 592-596.
Kart et al. (1997). Paediatr Anaesth. 7, 93-101.
Plante et al. (2010). Metabolism 59, S47-52.
Urban et al. (2010). Crit Rev Oncol Hematol. 73, 176-183.
Present study aimed to investigate if/how pain assessment was reported in all oncology protocols approved by Italian ethical committees and recorded in 2008 in a database of the National Monitoring Centre of Clinical Trial of the Italian Medicines Agency (AIFA).
Among protocols involving cancer diseases likely associated with pain - selected by an expert oncologist -, those including pain treatment and measurement, were identified by searching the texts for the following themes: “pain*” combined (using the Boolean operator “and”) “supportive care” or “pain management” or “pain treatment” or “analgesic*” or “morphin*” or “opioid*” or “opiate”. In a second search the themes “vas” or “nrs” or “vns” or “vrs*” or “vds*” or “quality of life” were used. Protocols including these themes were then independently reviewed by two investigators. To validate the search strategy, 10% of excluded protocols were randomly selected for further review.
One hundred and forty-three protocols were reviewed, 58 (40.6%) were investigator initiated studies, the others were promoted and sponsored by drug companies. Seventy-nine studies (55.2%) concerned phase II clinical trials, 29 (20.3%) were on lung cancer, 20 (14.0%) on breast cancer, and 16 (11.2%) on colorectal cancer. In 52 (36.4%) protocols pain treatment was mentioned, 35 (67.3%) included analgesics generic use, 11 (21.2%) included opiates use - but only 2 of these 11 reported specific guidelines -, and 6 (11.5%) included pain treatment without mentioning any drugs. Moreover, in 26 (18.2%) protocols supportive care was mentioned but not specifying pain. None of the protocols took into account the breakthrough cancer pain. As concern pain measure, 53 (37.1%) protocols considered pain measurement, of these 9 (17.0%) adopted a specific questionnaire focused on pain (Brief Pain Inventory, McGill Pain, Present Pain Intensity Questionnaires) and 44 (83.0%) adopted questionnaire about quality of life (EORTC, QLQ, FACT, EQ5D Questionnaires) including at least a specific item on pain. Twenty-five (17.5%) protocols included both pain treatment and measurement.
Our data indicates that in 2008 pain assessment and treatment were still not reported as it should have been in oncology clinical study protocols. The present analysis should be replicated including all oncology protocols recorded after the approval of the law 38 in 2010. Finally, ethical committees should pay close attention on pain therapy when evaluating oncology clinical study protocols.
Apolone et al. (2009). Br J Cancer 100, 1566-1574.
Cleeland et al. (1994). N Engl J Med. 330, 592-596.
Kart et al. (1997). Paediatr Anaesth. 7, 93-101.
Plante et al. (2010). Metabolism 59, S47-52.
Urban et al. (2010). Crit Rev Oncol Hematol. 73, 176-183.