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Management of cancer pain. Volume 1. Volume 2: evidence tables |
Goudas L, Carr D B, Bloch R, Balk E, Ioannidis J P, Terrin N, Gialeli-Goudas M, Chew P, Lau J |
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Authors' objectives To determine the prevalence of cancer-related pain and the efficacy of drug and non-drug therapies for its treatment. This abstract will focus only on the effectiveness of treatment.
Supplemental investigations were made into the side-effects of the different opioid analgesics, and the morbidity and mortality of cordotomy in treating cancer pain.
Searching MEDLINE, Cancerlit and the Cochrane Controlled Trials Register were searched from 1966 to 1998 for English language studies; the search terms were listed. Additional searches were conducted by checking the bibliographies of meta-analyses and selected review articles, and by consulting technical experts. The MEDLINE search was updated to October 1999 for the purpose of the supplemental questions.
Study selection Study designs of evaluations included in the reviewSpecific inclusion criteria relating to the study design were not stated. The included studies consisted of randomised and non-randomised controlled trials. Non-randomised studies that addressed the supplemental objectives were eligible. Where there were more than 10 non-randomised studies on a particular topic, minimum study size criteria were implemented.
Specific interventions included in the reviewStudies eligible for inclusion were those evaluating analgesics (alone or adjuvant); different formulations and routes of administration; palliative pharmacological (e.g. chemotherapy) and non-pharmacological cytotoxic or cytostatic therapy; and non-pharmacological physical or psychological treatment, or invasive surgical and non-surgical treatments (e.g. acupuncture and nerve blocks). The included studies evaluated an extensive range of treatments. The analgesics evaluated included non-steroidal anti-inflammatory drugs (NSAIDs) and opioids; palliative therapies included chemotherapy, bisphosphates and calcitonin; non-pharmacological cytotoxic or cytostatic therapies included radiation and radionuclides; non-pharmacological physical or psychological treatment included reflexology and acupuncture; and invasive surgical and non-surgical treatments included acupuncture and nerve blocks.
Participants included in the reviewStudies that consisted completely or partly of cancer patients were eligible for inclusion. Patients with pain resulting from direct tumour involvement, procedural pain, or pain from the side-effects of treatment were eligible. Studies of post-operative pain due to surgery for the treatment of cancer were excluded. No restrictions were imposed on age, gender or ethnicity of the patients, or the type and advancement (stage) of the cancer.
Outcomes assessed in the reviewPain measured as a primary or secondary outcome by any pain assessment instrument was eligible. A range of measures were used to assess pain in the studies, including visual analogue scales (VAS).
How were decisions on the relevance of primary studies made?Two reviewers selected the studies for inclusion. It was not stated how any disagreements were resolved.
Assessment of study quality The validity of each included study was assessed by assigning a grade according to the likelihood for bias for four dimensions of study quality: internal validity, applicability, study size, and magnitude of the treatment effect. The randomised controlled trials (RCTs) were graded for internal validity: A corresponded to a double-blinded trial with well-concealed randomisation, few drop-outs, and no or minor reporting problems; B corresponded to a single-blinded trial with unclear concealment of randomisation, and some inconsistency in reporting; C corresponded to an unblinded trial with inadequate concealment of random allocation, high drop-out rate, or substantial inconsistencies in reporting; and I corresponded to a trial that was inadequately reported.
The non-randomised studies were also graded for internal validity: A corresponded to a prospective controlled trial; B corresponded to a cohort; and C corresponded to a case series. Adequacy of reporting in non-randomised studies was graded as follows: 1, completely or mostly described; 2, fair reporting but some important data are missing; and 3, interpretation is difficult because many data are missing. The applicability of the non-randomised studies was also assessed.
The authors did not state how the papers were assessed for validity, or how many reviewers performed the validity assessment.
Data extraction The data were extracted by one reviewer and checked by a second. It was not stated how any disagreements were resolved.
The data were used to derive a magnitude of effect for the difference between the control and experimental groups. For studies that used a VAS, the effect size assigned ranged from a large difference in effect (greater than 20 mm change on 0- to 100-mm VAS between the control and experimental groups) to no difference in effect (0 to 4 mm change on 0- to 100-mm VAS between the control and experimental group). For studies that evaluated drug consumption, pain relief, quality of life indices, and pain management using other types of measures, experts assigned an effect size ranging from large beneficial effect to no beneficial effect. Data were extracted on a number of study details and presented in tables, which were available in a second volume of the report.
Methods of synthesis How were the studies combined?The studies were tabulated and presented in a narrative synthesis according to the different treatments evaluated in the included studies. The RCTs were combined in meta-analyses for each key question when a sufficient number of trials with similar study characteristics (e.g. assessment instrument) were available.
How were differences between studies investigated?Information on the treatment type, study quality, results and effect of each included study were tabulated and compared. The studies were grouped according to six treatment categories: primary pharmacological interventions, secondary pharmacological interventions, non-pharmacological interventions, non-pharmacological invasive interventions, antineoplastic interventions, and other various treatment interventions.
Results of the review One hundred and eighty-eight RCTs and 100 non-randomised studies were included.
Only the main results were presented herein. Further analyses of cancer-related pain and methodological quality were available in the full report.
The overall methodological quality and reporting of the treatment studies was poor.
Current analgesics. The studies did not differentiate the relative efficacy of opioids and NSAIDs administered through various routes to patients with mild, moderate, or severe cancer-related pain. An opioid dose-sparing effect was observed through the co-administration of NSAIDs; however, there was no consistent reduction in the side-effects. There was insufficient evidence to determine the relative efficacy of different NSAIDs, and no significant difference in analgesic benefit between NSAIDs and 'weak' opioids was found. One RCT suggested that oral transmucosal fentanyl citrate was superior to placebo in the treatment of breakthrough pain. No studies were found that evaluated the analgesic efficacy of NSAIDs selective for the cyclooxygenase-2 isozyme in the treatment of cancer pain.
Different formulations and routes of administration. There was no evidence of a difference in analgesic efficacy, side-effects, or patient preference between different modes of administration or formulations.
Palliative pharmacological and non-pharmacological cytotoxic or cytostatic therapy. Biphosphonates were shown to be effective in reducing bone pain in patients receiving tumour-directed therapy; this benefit may be relatively less with combined therapies. There was no strong evidence of a benefit of chemotherapeutic or hormone therapy regimens. Although external radiation decreased pain, there was no sustained difference in pain between fractionation schedules.
Adjuvant physical or psychological treatments. Few studies investigated these treatments and the variability in the types of intervention precludes any broad conclusions.
Invasive surgical and non-surgical treatments. The use of neurolytic celiac plexus block was associated with pain relief in pancreatic and other visceral cancers. There was insufficient evidence to determine the effectiveness of spinally administered opioids or other agents, or ablative neurosurgical therapies such as cordotomy or rhizotomy. No included trials investigated the efficacy of acupuncture.
Authors' conclusions Many current treatment modalities can individually reduce cancer pain. However, the evidence represents only a fraction of that which exists, and many clinical questions remain unanswered and preclinical insights untranslated because of a lack of high-quality evidence.
CRD commentary The review addressed a wide range of questions encompassing several treatment alternatives. This contributed to the broad inclusion criteria. The authors used procedures to minimise bias when selecting the studies for inclusion and protected against errors in the data extraction process. The search for studies was extensive and sought to identify unpublished studies, although there was potential for language bias since the papers had to be published in English.
The presentation of the results in a narrative summary was appropriate, owing to the heterogeneity of the included studies, and study quality was assessed systematically. Meta-analyses were conducted when appropriate. The review offered an objective summary of the evidence pertaining to the treatment of cancer-related pain, and the recommendations for future research were based on the evidence presented.
Implications of the review for practice and research Practice: The authors did not state any implications for practice.
Research: The authors stated that further methodologically robust studies with a greater number of patients and of longer duration, and with cancer pain relief as the primary outcome, are required. These studies should investigate the influence of age, gender, race, psychosocial context and cultural issues on pain relief. There is also need for research in paediatric populations and on quality of life issues. Further research to ascertain the most effective combination of drug and non-drug interventions is required. In addition, the route of administration needs to be assessed with regards to patient preference, comparative efficacy, and the use of initial or secondary agents, or a combination. Systematic reviews of the best available evidence are required until the larger trials are accomplished and accepted.
Funding Agency for Healthcare Research and Quality, contract number 290-97-0019.
Bibliographic details Goudas L, Carr D B, Bloch R, Balk E, Ioannidis J P, Terrin N, Gialeli-Goudas M, Chew P, Lau J. Management of cancer pain. Volume 1. Volume 2: evidence tables. Rockville, MD, USA: Agency for Healthcare Research and Quality. Evidence Report/Technology Assessment; 35. 2001 Other publications of related interest US Dept. of Health and Human Services, Agency for Health Care Research and Quality. Management of cancer pain Evidence Report Technology Assessment: number 35 - management of cancer pain summary. J Pain Palliat Care Pharmacother 2002;16:91-102.
This additional published commentary may also be of interest. Mohide EA. Review: NSAIDs and adjuvant treatments such as hypnosis can help to reduce cancer related pain. Evid Based Nurs 2002;5:115.
Indexing Status Subject indexing assigned by CRD MeSH Acupuncture Therapy; Analgesics, Opioid /therapeutic use; Anti-Inflammatory Agents, Non-Steroidal /administration & Massage; Neoplasms /complications; Pain /drug therapy; Pain Measurement; Palliative Care; dosage /therapeutic use AccessionNumber 12002008296 Date bibliographic record published 31/07/2005 Date abstract record published 31/07/2005 Record Status This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn. |
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