Cancer Pain Management: An Italian Delphi Survey from the Rational Use of Analgesics (RUA) Group.

BACKGROUND: In patients with cancer, the prevalence of pain is high, and pain management is often challenging despite the wide availability of drugs and guidelines. METHODS: This Delphi survey was organized within the Rational Use of Analgesics (RUA) Group projects to reach a consensus among Italian palliative care specialists on pain assessment and management. Items were identified from recent publications on cancer pain and guidelines. RESULTS: This survey included input from 190 palliative care specialists representing all Italian territory. A consensus was reached on 17 statements. Items concerning pain assessment achieved over 70% agreement amongst the participants. Items on principles of pain management and management according to type of pain, including breakthrough cancer-related pain and neuropathic pain also achieved high levels of agreement. CONCLUSION: Results from the RUA project showed that Italian palliative care specialists had a particular interest in items related to pain challenges, in addition to the evaluation and control of pain associated with cancer. However, some discrepancies between current guidelines and clinical practice were observed.

Euthanasia and physician-assisted suicide: A white paper from the European Association for Palliative Care.

BACKGROUND: In recognition of the ongoing discussion on euthanasia and physician-assisted suicide, the Board of Directors of the European Association for Palliative Care commissioned this white paper from the palliative care perspective. AIM: This white paper aims to provide an ethical framework for palliative care professionals on euthanasia and physician-assisted suicide. It also aims to provide an overview on the available evidence as well as a discourse of ethical principles related to these issues. DESIGN: Starting from a 2003 European Association for Palliative Care position paper, 21 statements were drafted and submitted to a five-round Delphi process PARTICIPANTS: A panel with 17 experts commented on the paper in round 1. Board members of national palliative care or hospice associations that are collective members of European Association for Palliative Care were invited to an online survey in rounds 2 and 3. The expert panel and the European Association for Palliative Care board members participated in rounds 4 and 5. This final version was adopted as an official position paper of the European Association for Palliative Care in April 2015. RESULTS: Main topics of the white paper are concepts and definitions of palliative care, its values and philosophy, euthanasia and physician-assisted suicide, key issues on the patient and the organizational level. The consensus process confirmed the 2003 European Association for Palliative Care white paper and its position on the relationship between palliative care and euthanasia and physician-assisted suicide. CONCLUSION: The European Association for Palliative Care feels that it is important to contribute to informed public debates on these issues. Complete consensus seems to be unachievable due to incompatible normative frameworks that clash.

Episodic (breakthrough) pain prevalence in a population of cancer pain patients. Comparison of clinical diagnoses with the QUDEI--Italian questionnaire for intense episodic pain.

CONTEXT: Breakthrough/episodic pain (BP-EP) diagnosis is often based on clinical experience, and different opinions exist, even among palliative care clinicians, about its definition and application to clinical practice. OBJECTIVES: The primary aim of this study was to assess the prevalence and clinical characteristics of BP-EP in an unselected Italian population of patients with cancer-related chronic pain, based on clinical diagnosis and on the use of an assessment tool, the Questionnaire for Intense Episodic Pain (QUDEI). METHODS: A cross-sectional multicenter prevalence study of 240 consecutive cancer pain patients was carried out. The physicians participating in the study attended a training session aimed at defining and recognizing BP-EP. The QUDEI, a screening and assessment tool based on patient interview, diagnosed the presence of BP-EP in patients regularly taking analgesics for the previous three days and who had at least one pain flare in the previous 24 hours. Clinical evaluation and questionnaire application were carried out by different health care providers. RESULTS: The estimated prevalence of BP-EP was 73% (95% confidence interval [CI] = 67%, 79%) when the diagnosis was made by physicians and 66% (95% CI = 60%, 72%) when the QUDEI was applied (86% agreement). When only patients with baseline pain less than or equal to six were included in the analysis, the above prevalences decreased to 67% and 60%, respectively. CONCLUSION: Because BP-EP is a significant phenomenon in cancer pain management, its appropriate recognition requires a more widely, internationally accepted general definition and specific validated tools for its screening and evaluation.

Use of opioid analgesics in the treatment of cancer pain: evidence-based recommendations from the EAPC.

Here we provide the updated version of the guidelines of the European Association for Palliative Care (EAPC) on the use of opioids for the treatment of cancer pain. The update was undertaken by the European Palliative Care Research Collaborative. Previous EAPC guidelines were reviewed and compared with other currently available guidelines, and consensus recommendations were created by formal international expert panel. The content of the guidelines was defined according to several topics, each of which was assigned to collaborators who developed systematic literature reviews with a common methodology. The recommendations were developed by a writing committee that combined the evidence derived from the systematic reviews with the panellists' evaluations in a co-authored process, and were endorsed by the EAPC Board of Directors. The guidelines are presented as a list of 16 evidence-based recommendations developed according to the Grading of Recommendations Assessment, Development and Evaluation system.

Palliative sedation at the end of life at a tertiary cancer center.

PURPOSE: The aim of this study was to describe the use of palliative sedation (PS) its indications and outcomes in patients followed up till death by an inpatient palliative care consult team (PCCT) at a tertiary cancer center. METHODS: All patients referred for 5 years to the PCCT and followed up till death were eligible for the study. Both PCCT recordings and hospital charts were reviewed and a codified assessment was performed. RESULTS: Over a total of 2,033 consecutive consults, 129 patients died during admission and were eligible. Eighty-three had the indication to PS, 4% of all consults (95% confidence interval [95%CI], 3% to 5%) and 64% of eligible patients (95%CI, 56% to 73%). PS was more frequently indicated in males and in patients with recurrent dyspnea and recurrent agitation, while it was less frequently indicated in older people and in patients with cerebral metastases and recurrent drowsiness. The most frequent indications to PS were dyspnea (37%) and delirium (31%) alone or combined with other symptoms. PS was successfully achieved in 69 patients; the drugs most frequently used for PS were midazolam (46%), haloperidol (35%), and chlorpromazine (32%) and opioid dose escalation was higher in sedated patients (P < 0.01). CONCLUSIONS: PS is an important intervention in the management of terminal disease by a consulting palliative care team. Improved collaboration and communication between the hospital staff and the PCCT should be offered to meet patients' needs when PS is required.

Awareness, understanding and attitudes of Italians regarding palliative care.

There are numerous difficulties encountered in the diffusion of palliative care (PC) in developed countries. A correct and widespread awareness of PC among the general public represents an important factor for its enhanced diffusion and use. The aim of this study is to verify the level of awareness of PC among Italians and their perception of the needs of patients with incurable illness. A random sample of 1897 adult subjects, aged 18 to 74 years, representative of the Italian population, was interviewed after stratification by gender, age (6 strata), education (3 levels), geographic area of residency (4 areas) and town of residency (4 dimensions). 59.4% of those interviewed had heard of PC, but only 23.5% of them believed that they had an adequate or precise idea of what PC is; 27% of them did not know or had a mistaken idea about the nature of PC. The most accepted perception was that PC alleviates pain and improves quality-of-life. The principal concerns attributed to incurable patients were: fear of suffering and of death, and the principal needs were perceived as: relief from pain and physical suffering. The primary needs of the family were identified in: medical and nursing care at home, followed by: care provided by volunteers and psychological support. The most appropriate care-setting for these patients was indicated as their home, possibly with the support of professional carers. In the case of children, the main concern indicated was that of being "separated" from family, friends, home and toys. Only 45.2% of interviewees thought that they knew a person who had experienced PC. In conclusion, the awareness of the Italian population of PC is scarce and often incorrect. In order to achieve a greater diffusion and better use of PC in our country, this awareness needs to be improved by appropriate intervention.

Effects of transdermal buprenorphine on patients-reported outcomes in cancer patients: results from the Cancer Pain Outcome Research (CPOR) Study Group.

OBJECTIVES: Pain still afflicts most cancer patients, mainly in the metastatic phases, and under-treatment is well documented. Transdermal delivery systems (TDS) containing fentanyl or buprenorphine could potentiality have advantages over oral and parenteral routes, but evidence from comparative trials are scanty. In the framework of a wider initiative, an Outcome Research Study was carried out in Italy in 2006 to evaluate the effects of various analgesic options, particularly buprenorphine TDS. METHODS: This is a multicenter, open-label, prospective, nonrandomized study. Data were collected using a web-based standardized system, with a follow-up up of to 3 months. Pain intensity, the primary outcomes of the study, was measured using 11-point numerical rating scales from the Brief Pain Inventory. RESULTS: One-hundred ten centers recruited 1801 cases, most of which (60%) were receiving a strong opioid at the time of inclusion. Of these, 257 had TDS buprenorphine as first choice. Of the remaining 709 patients who at the time of inclusion were not on a strong opioid, 325 changed to a strong opioid and in 43% it was TDS buprenorphine. During the follow-up, physicians had to increase the dosage to control pain (average increase between 16% and 17%). About 34% of patients had an improvement of at least 2 points in worst pain, 15% had a 20% improvement in pain relief, and 40% in satisfaction. Results were in line with those of patients receiving other World Health Organization-level III opioids. CONCLUSIONS: Despite the limitations owing to the observational design, these findings may be useful to clinicians to judge the value of the drug under evaluation better and to help researchers design further comparative studies.

Normal-release oral morphine starting dose in cancer patients with pain.

OBJECTIVES: To evaluate whether the current European Association for Palliative Care recommendation regarding the starting dose of 5 mg of normal-release morphine (NRM) sulfate oral solution every 4 hours in opioid naive patients or 10 mg in patients already being treated with "weak" opioids is effective and could be proposed as starting routine dose in clinical practice. Secondary aims were to estimate the percentage of patients who were high responders to NRM and to study the association of baseline patient characteristics with both high analgesic responsivity and the need of opioid dose escalation. METHODS: Consecutive strong opioid-naive patients with cancer pain were enrolled in a multicenter uncontrolled phase 4 clinical trial. Oral NRM was administered at 2 different dosages: 5 and 10 mg every 4 hours, respectively, for opioids-naive (group A) and nonopioids-naive (group B) patients as starting therapy. Average daily dosages of NRM and opioid escalation index (OEI) were calculated and the reduction in pain score was tested through Student t test both in group A and in group B patients. RESULTS: One hundred fifty-nine consecutive patients were enrolled and data analysis was conducted on 151 (95%) patients. On an average the OEIs were: 3.2 in group A and 6.5 in group B and a significant reduction in pain score both after 3 and 5 days from baseline (P<0.001) was shown in both groups. In multivariate analysis both Karnofsky Performance Status and episodic pain showed to be independent prognostic factors of a high analgesic response. The presence of neuropathic pain showed to be associated with a higher OEI. DISCUSSION: These data show that empiric standard doses of NRM during titration, recommended by European Association for Palliative Care, are effective in clinical practice.

Intensity and treatment of symptoms in 3,030 palliative care patients: a cross-sectional survey of the EAPC Research Network.

OBJECTIVE: This study aimed to describe intensity and treatment of symptoms other than pain in European palliative care units. PATIENTS: A total of 3,030 patients, including 2,064 that used an opioid, were included from 143 palliative care centers, in 21 European countries. RESULTS: Pain was treated with analgesics corresponding to the WHO pain ladder step I (n = 374), II (n = 497), and III (n = 1,567). Frequencies of symptoms observed as moderate or severe were for generalized weakness (50 percent), fatigue (48 percent), anxiety (28 percent), anorexia (26 percent), constipation (18 percent), focal weakness (18 percent), depression (18 percent), and dyspnoea (15 percent). When comparing WHO-groups, cancer diagnoses, metastasis sites, countries, and genders, we found that some of the symptom intensities and treatments differed significantly between subgroups. A majority of patients used drugs for symptom management. Still, more than one-third of patients assessed to have moderate or severe constipation did not receive any treatment. The corresponding numbers for depression, confusion, nausea, vomiting, or anxiety were approaching 40 percent and for poor sleep about 50 percent. Prescription practice of antiemetics, laxatives, and psychotropic drugs varied widely between countries both in terms of preparation and percent of patients receiving a specific treatment. CONCLUSIONS: This survey shows that clinically relevant symptoms are frequent and that one-third to half of the patients with a symptom observed as moderate or severe do not receive any treatment aimed to reduce the symptom intensity. Several symptoms and treatments differed between WHO-groups, cancer diagnoses, metastasis locations, countries, and genders. Prescription practice varied between countries both in terms of medication administered and percent of patients receiving specific treatment.

Decreases in pain at rest and movement-related pain during zoledronic acid treatment in patients with bone metastases due to breast or prostate cancer: a pilot study.

BACKGROUND: In patients with bone metastases, pain may be absent or moderate at rest, but may be exacerbated by different movements or positions. No study has evaluated separately pain at rest and on movement in patients with bone metastases undergoing treatment with zoledronic acid (ZA). AIM: The aim of this prospective observational study was to evaluate the reduction in intensity of pain at rest and in movement-related pain after treatment with up to six infusions of ZA 4 mg every 28 days in patients with painful bone metastases due to breast or prostate cancer cared for at the Oncological Units and Pain Therapy and Palliative Care Unit of the NCI of Milano. MATERIALS AND METHODS: Pain was assessed by a six-level verbal rating scale (0-5 score) at baseline and on each infusion as well as at follow-up visits (2 weeks after every infusion). The two main endpoints (estimated reduction in pain and movement-related pain) were defined as the difference between the baseline score and the average of all the post-treatment scores for each patient. To allow for the potential confounding effect of analgesic consumption, patients without any increase in analgesic consumption during zoledronic acid treatment were also analyzed as a separate subgroup. RESULTS: Forty-eight patients with breast (34) or prostate cancer (14) were enrolled. At baseline, 100% of the patients had pain on movement, in 65% of them, the intensity ranged from moderate to very severe, in 61% of the patients, the intensity of pain on movement was higher than the intensity of pain at rest (average difference 0.89; 95% CI, 0.5-1.30). The estimated mean intensity reduction of pain at rest and on movement was: (a) 0.62 (95% CI, 0.28-0.98) and 0.79 (95% CI, 0.43-1.14), respectively, during the first 90 days of ZA treatment; (b) 0.59 (95% CI, 0.23-0.96) and 0.86 (95% CI, 0.49-1.23), respectively, during the entire treatment and follow-up period. Analgesic consumption decreased or was stable on average in 31 and 27%, respectively, of available follow-up data. In the 14 patients with decreased or stable analgesic consumption, pain reduction was 0.61 and 1.01, respectively. CONCLUSIONS: In this study, at baseline, all the patients with painful bone metastases experience movement-related pain, and during zoledronic acid treatment, a decrease for both pain at rest and on movement was obtained.

Patient demographics and centre description in European palliative care units.

Patients in palliative care are elderly, frail and in decline with multisystem disease. These and other factors make palliative care research particularly challenging, and has been one of several reasons why relatively little systematic research has been performed. The European Association for Palliative Care (EAPC) is seeking to emphasise the importance of research. The present project is the first empirical multicentre study organised by the EAPC Research Network, with the aim of identifying the patient population using specialised palliative care, and identifying a network of palliative care services across Europe, able to participate in a multicentre collaboration for research. During a designated week in the autumn of 2000, data on patients were recorded from 143 centres. The survey was carried out by means of two questionnaires, one centre questionnaire and one patient questionnaire. Data were submitted on 3013 patients from 22 different European countries. Almost all patients had cancer (94%), while some had neurological disease (3%). The majority (75%) had been referred to a palliative care service during the six to seven months before the survey was performed. Very few patients had less than one week of expected survival (6%), the majority were expected to live one to six months, while as many as 16% were expected to live more than one year. The majority of the patients (27%) were fully ambulatory--the ability to walk independently without any assistance. The majority of the patients (60%) received care as an outpatient, either at a traditional clinic in an outpatient cancer hospital (12%), in home-care programs from a specialised advisory service (24%), or external nursing care (24%). The population of patients included in this survey was not a sample of dying patients. There were a substantial number of patients with an anticipated life expectancy of more than six months. The study demonstrated a considerable enthusiasm for research in the palliative care community across Europe. The heterogeneity of the sample is evident, and this will need careful consideration for future clinical trials. This calls for an international consensus on how to report on patient characteristics within palliative care research. This is necessary in order to be able to evaluate the representativity of the study population, as well as to compare data between studies. The range of services encountered in the survey highlights the need for the organisational and clinical standards for palliative care, which can be audited.

Pain assessment tools: is the content appropriate for use in palliative care?

Inadequate pain assessment prevents optimal treatment in palliative care. The content of pain assessment tools might limit their usefulness for proper pain assessment, but data on the content validity of the tools are scarce. The objective of this study was to examine the content of the existing pain assessment tools, and to evaluate the appropriateness of different dimensions and items for pain assessment in palliative care. A systematic search was performed to find pain assessment tools for patients with advanced cancer who were receiving palliative care. An ad hoc search with broader search criteria supplemented the systematic search. The items of the identified tools were allocated to appropriate dimensions. This was reviewed by an international panel of experts, who also evaluated the relevance of the different dimensions for pain assessment in palliative care. The systematic literature search generated 16 assessment tools while the ad hoc search generated 64. Ten pain dimensions containing 1,011 pain items were identified by the experts. The experts ranked intensity, temporal pattern, treatment and exacerbating/relieving factors, location, and interference with health-related quality of life as the most important dimensions. None of the assessment tools covered these dimensions satisfactorily. Most items were related to interference (231) and intensity (138). Temporal pattern (which includes breakthrough pain), ranked as the second most important dimension, was covered by 29 items only. Many tools include dimensions and items of limited relevance for patients with advanced cancer. This might reduce compliance and threaten the validity of the assessment. New tools should reflect the clinical relevance of different dimensions and be user-friendly.

Is the use of transdermal fentanyl inappropriate according to the WHO guidelines and the EAPC recommendations? A study of cancer patients in Italy.

BACKGROUND: World Health Organization (WHO) guidelines, Agency for Health Care Policy and Research (AHCPR) clinical practice guidelines, and EAPC recommendations indicate oral route of opioid administration as the preferred route. Transdermal administration of opioids is considered an alternative when patients cannot take medications orally. Moreover, WHO and EAPC indicate orally administered morphine as the first-choice drug for the treatment of moderate to severe cancer-related pain. However, we can see that in Italy there is an increasing use of transdermal fentanyl (TF) as first-choice strong opioid (and route) even when oral administration of opioids is possible. AIMS: The aims of this study are to describe the modality in the use of TF administration in two settings of care, taking into consideration (1) the drugs previously taken by the patients, (2) the reasons for switching from any drug to TF, (3) the conversion ratio used, and (4) the frequency of "inappropriate use of transdermal fentanyl according to the WHO guidelines and the EAPC recommendations", i.e., switching to fentanyl patch from any drug, even if there were no contraindications in using oral morphine. The settings of care considered were the out-patient palliative care unit (OP-PCU) and the oncological wards (OWs) of the National Cancer Institute (NCI) of Milan. PATIENTS AND METHODS: The clinical charts of 98 patients prescribed with and given fentanyl patch for the first time at the NCI of Milan in 2002 were reviewed and the data gathered were grouped according to the administration of fentanyl at the OP-PCU (63 out-patients) or at the OWs (35 in-patients). Summary descriptive statistics and bar and box plots have been used. Fisher two-tailed exact text was applied to test the differences between in- and out-patients. RESULTS: Before switching to TF, (1) in-patients were more frequently treated with nonsteroidal anti-inflammatory drugs (NSAIDs) and weak opioids (mostly tramadol) in respect to the out-patients (44.1 vs 25.8%) who were mostly treated with oral morphine (48.4 vs 20.6%) (p=0.045), and (2) 88.7% of the out-patients were treated with oral opioids and only 1.6% with parenteral opioids in respect to OWs where 69.7% were on oral opioids and 18.2% on parenteral opioids (p=0.006). In 29% of out-patients and in 53% of in-patients, changing to fentanyl patch was considered as "inappropriate" (p=0.028) according to the WHO guidelines and the EAPC recommendations. No statistically significant differences between the two settings were observed regarding the reasons for switching and the conversion ratio used. CONCLUSIONS: There is a trend to use fentanyl patch as first-choice strong opioid in cancer patients in situations such as titration phase, in the presence of instable pain, and in the absence of dysphagia or gastrointestinal symptoms where the use of oral morphine is, however, not contraindicated.

Pain in cancer. An outcome research project to evaluate the epidemiology, the quality and the effects of pain treatment in cancer patients.

BACKGROUND: Management of pain related to advanced or metastatic cancer, although the availability of several pharmacological and non-pharmacological interventions and the existence of well-known guidelines and protocols, is often difficult and inadequate. Evidence of the relative effectiveness of current options for treating cancer pain from comparative randomized studies is scanty. METHODS: In the context of a wider project, a multicenter, open label, prospective Outcome Research study will be launched in Italy in 2006 to investigate the epidemiology of cancer pain and of its treatments, the quality of analgesic-drug therapy and the effectiveness of alternative analgesic strategies in a large, prospective, unselected cohort of cancer patients using the state-of-the art of patient-reported-outcomes. About 100 Italian centers will recruit 2500 patients with advanced/progressive/metastatic cancer with pain (related to the cancer disease) requiring analgesic treatments. Each center is expected to recruit 25 consecutive and eligible patients during the study inception period. Approximately two months will be allowed for subject recruitment and enrollment. Subject evaluation and follow-up will be for 3 months. The effect on outcomes of various therapeutic analgesic options administered by physicians, given the observational approach where patients are not assigned at random to different treatments, will be compared using the propensity score approach, allowing the adjustment for treatment selection bias. Later, after the launch of the observational study and on the basis of results, in specific subsamples of patients and in select centers of the network, a Randomized Controlled Trial will be carried out to formally compare the efficacy of alternative analgesic strategies, with particular emphasis on oral morphine (as comparator) and buprenorphine patch (as experimental arm). Results from the outcome (cohort) and experimental (Randomized Controlled Trial) studies will ensure both the external and internal validity.

Pain and pain treatments in European palliative care units. A cross sectional survey from the European Association for Palliative Care Research Network.

The Research Network of the European Association for Palliative Care (EAPC) performed a survey of 3030 cancer patients from 143 palliative care centres in 21 European countries. The survey addressed pain intensity and the use of non-opioid analgesics, adjuvant analgesics and opioids. Patients were treated with analgesics corresponding to the WHO pain ladder step I (n = 855), step II (n = 509) and step III (n = 1589). The investigators assessed 32% of the patients as having moderate or severe pain. In general there were small differences between pain intensities across different countries. Cancer primary sites and the presence of metastasis had only minor influences on pain intensity. The most frequently used non-opioid analgesics were NSAIDs (26%) and paracetamol (23%). Adjuvant analgesics or co-analgesics used by >1% of the patients were corticosteroids (39%), tricylic antidepressants (11%), gabapentin (5%), bisphosphonates (4%), clonazepam (2%), carbamazepine (4%) and phenytoin (2%). The use of non-opioid analgesics and co-analgesics varied widely between countries. Opioids administered for mild to moderate pain were codeine (8%), tramadol (8%), dextropropoxyphene (5%) and dihydrocodeine (2%). Morphine was the most frequently used opioid for moderate to severe pain (oral normal release morphine: 21%; oral sustained-release morphine: 19%; i.v. or s.c. morphine: 10%). Other opioids for moderate to severe pain were transdermal fentanyl (14%), oxycodone (4%), methadone (2%), diamorphine (2%) and hydromorphone (1%). We observed large variations in the use of opioids across countries. Finally, we observed that only a minority of the patients who used morphine needed very high doses.

Prognostic factors in advanced cancer patients: evidence-based clinical recommendations--a study by the Steering Committee of the European Association for Palliative Care.

PURPOSE: To offer evidence-based clinical recommendations concerning prognosis in advanced cancer patients. METHODS: A Working Group of the Research Network of the European Association for Palliative Care identified clinically significant topics, reviewed the studies, and assigned the level of evidence. A formal meta-analysis was not feasible because of the heterogeneity of published studies and the lack of minimal standards in reporting results. A systematic electronic literature search within the main available medical literature databases was performed for each of the following four areas identified: clinical prediction of survival (CPS), biologic factors, clinical signs and symptoms and psychosocial variables, and prognostic scores. Only studies on patients with advanced cancer and survival < or = 90 days were included. RESULTS: A total of 38 studies were evaluated. Level A evidence-based recommendations of prognostic correlation could be formulated for CPS (albeit with a series of limitations of which clinicians must be aware) and prognostic scores. Recommendations on the use of other prognostic factors, such as performance status, symptoms associated with cancer anorexia-cachexia syndrome (weight loss, anorexia, dysphagia, and xerostomia), dyspnea, delirium, and some biologic factors (leukocytosis, lymphocytopenia, and C-reactive protein), reached level B. CONCLUSION: Prognostication of life expectancy is a significant clinical commitment for clinicians involved in oncology and palliative care. More accurate prognostication is feasible and can be achieved by combining clinical experience and evidence from the literature. Using and communicating prognostic information should be part of a multidisciplinary palliative care approach.

Opioid purchases and expenditure in nine western European countries: 'are we killing off morphine?'.

BACKGROUND: In clinical practice the major role of opioid drugs is the management of malignant and nonmalignant pain. The primary aim of this study is to evaluate the trend in sales of four opioid analgesic drugs (codeine, tramadol, morphine, fentanyl), from wholesalers to community pharmacies, as an indicator of opioid consumption in nine European countries in 2001, 2002 and 2003. Secondary aims are to compare: (a) the amount of each drug purchased by different countries in 2003; (b) the average price for each drug in the different countries in 2003; and (c) the total expenditure for each opioid from 2001 to 2003. METHODS: Data from the Statistical Report on drugs purchased by pharmacies was supplied by IMS Health, an internationally accepted information provider for the pharmaceutical and health care industries. FINDING: In the period 2001 2003, while the percentage increase of purchases of fentanyl and tramadol was considerable, that of morphine was the lowest in most of the nine countries. The largest consumer of codeine was the UK and of tramadol was Belgium. The consumption of morphine was the lowest reported in all the countries together and was three times lower than that of transdermal fentanyl. There was a high variability in the costs of the opioids among the different countries. In 2003, the total expenditure for fentanyl reached the highest total expenditure [corrected] followed by codeine. Morphine presents the lowest expenditure in all nine countries and over all three years. INTERPRETATION: These results open up many questions. What factors influence opioid purchasing and costs in these European countries? It would be interesting to have the answers from those people who know the actual situation in the individual countries.

Cancer pain assessment in clinical trials. A review of the literature (1999-2002).

The aim of this review was to evaluate the methods of pain measurement in controlled clinical trials in oncology published between 1999 and 2002. An electronic literature search strategy was used according to established criteria applied to the Medline database and PubMed search engine. Articles were selected to include only studies that had chronic cancer pain as the primary or secondary objective of a controlled clinical trial. A specific evaluation scheme was used to examine how pain measurement methods were chosen and implemented in the study procedures. The search strategy identified 613 articles, and 68 were selected for evaluation. Most articles (69%) chose unidimensional pain measurement tools, such as visual analogue scales, numerical rating scales and verbal rating scales, whereas others used questionnaires. The implementation of the pain assessment method was problematic in many studies, especially as far as time frame of pain assessment (70%), administration modalities (46%), and use of non-validated measurement methods (10%). Design of study and data analysis were often unclear about the definition of pain outcome measure (40%), patient compliance with pain assessment (98%), and impact of missing data (56%). Statistical techniques were seldom appropriate to the type of data collected and often inadequate to describe the pain variable under study. It is clear from this review that most authors were aware of the need of valid pain measurement tools to be used in clinical trials. However, too often these tools were not appropriately used in the trial, or at least their use was not described with sufficient accuracy in the trial methods.