Six years' experience with interdisciplinary review teams in health technology assessment in Norway.

OBJECTIVES: The aim of this study was to evaluate the use of interdisciplinary review teams that have been the main and central work form in making health technology assessments at the Norwegian Centre for Health Technology Assessment. METHODS: Evaluation questionnaires were sent to all 112 participants in the 17 review teams for the period of January 1998 to June 2003 after completion of the literature assessment. Questions were on the theme/mandate of the assessments, composition of the review team, organization of the work, the working method, and update of the report. RESULTS: The teams ranged from 4 to 14 persons regarded as opinion leaders in their field. The project periods lasted from 4 to 33 months. In all, fifty-five participants gave fifty-eight responses (51.8 percent) to the questionnaires. A total of 83 percent thought the theme was well argued, and 62 percent thought the mandate for the assessments was sufficiently clear. Approximately 80 percent were positive to the composition of the review team. In all, 22 percent expressed that the work method was too extensive and 43 percent wanted more tuition. General comments were that the working method gave competence in assessing medical literature, relevant professional training, and tuition in a working method that ensured the legitimacy of their work. CONCLUSIONS: The review team participants were satisfied with most aspects of the work. The Norwegian Centre for Health Technology Assessment will continue using interdisciplinary review teams in making health technology assessments.

[Primary treatment of ovarian cancer]. / Primaerbehandling av ovarialcancer.

BACKGROUND: Patients with epithelial ovarian cancer are often diagnosed with advanced disease; hence they have a generally poor survival rate. The main objective was to assess the clinical effectiveness of the four main treatment options in the primary treatment of epithelial ovarian cancer: i) adjuvant chemotherapy and/or adjuvant radiotherapy, ii) cytoreductive surgery, iii) neoadjuvant chemotherapy in advanced disease, and iv) postoperative chemotherapy in advanced disease. MATERIAL AND METHODS: The scientific literature was identified by searches in Medline, Embase and Cochrane CCTR and by additional manual searches. Using criteria defined by protocol, two reviewers assessed each study according to relevance, quality and validity. Among 2227 publications identified, 635 were read as full-text articles, and 90 studies were critically assessed as relevant publications. All included studies were systematised in three subgroups according to the quality of the study design in question and the validity of the results: high, moderate, or low. A total of 45 studies of high or moderate quality form the documentary basis for this review. RESULTS: Current data are inconclusive regarding the effect of adjuvant chemotherapy. Retrospective data show a survival advantage for patients who have had maximum cytoreductive surgery. The effect of neoadjuvant chemotherapy is uncertain. Several questions remain unanswered despite wide acceptance of paclitaxel-carboplatin as the current standard in first-line treatment. INTERPRETATION: This systematic review demonstrates the need for more clinical studies.

Birth defects in children conceived by ICSI compared with children conceived by other IVF-methods; a meta-analysis.

BACKGROUND: Intracytoplasmic sperm injection (ICSI) is a method of assisted reproductive technology that involves the selection of a single sperm cell and the manual injection of this cell into the egg. The lack of relevant experimental studies, the nature of the technology involving non-natural selection of the fertilizing sperm, and possible damage to the egg have caused concern that ICSI could increase the risk of birth defects. Data from available cohort studies comparing ICSI with standard in vitro fertilization (IVF) should be combined to evaluate the risks involved with ICSI. METHODS: We reviewed more than 2500 titles and abstracts containing keywords related to ICSI and identified 22 scientific articles with data on birth defects among ICSI-births. A total of four peer-reviewed, non-overlapping prospective cohort studies provided reliable and comparable data on birth defects both for children conceived by ICSI and children conceived by standard IVF. These studies included a total of 5395 children born after ICSI. RESULTS: The pooled estimate of the risk of a major birth defect was a 1.12-fold increase after ICSI when compared with standard IVF (risk ratio = 1.12, 95% confidence interval (CI): 0.97-1.28, P = 0.12). There was no marked heterogeneity of risk ratios between these studies (P = 0.10). We found no significantly increased risks after ICSI for any of the categories cardiovascular defects, musculoskeletal defects, hypospadias, neural tube defects, or oral clefts. CONCLUSIONS: Our analysis does not indicate that the ICSI-procedure represents significant additional risks of major birth defects in addition to the risk involved in standard IVF. The data was limited, particularly on risks of specific categories of defects.

[Clinical use of haematopoietic stem cells from cord blood]. / Klinisk bruk av hematopoetiske stamceller fra navlestrengsblod.

A group of experts appointed by the Norwegian Centre for Health Technology Assessment (SMM) has undertaken a systematic review of available literature on the clinical effectiveness of transplanting haematopoietic stem cells from cord blood. A total of 17 studies form the documentary basis of the review. Autologous transplants of stem cells from cord blood have not been published. Retrospective studies suggest that the clinical effect of allogeneic cord blood transplants, at least in children, is comparable to transplants with allogeneic stem cells from bone marrow or peripheral blood cells. This review demonstrates the need for prospective studies comparing transplantations of cord blood with bone marrow or peripheral blood stem cells.

Status and potential of gene therapy in clinical medicine. Assessment of an emerging health technology through systematic survey of clinical gene therapy protocols and published results.

OBJECTIVE: Somatic gene therapy is a new method in the rapidly expanding field of molecular medicine. Due to recent encouraging results and the promising prospect for some disease groups, Norwegian health authorities wanted to assess somatic therapy with evidence-based standards for strategic use. This article presents the results of this assessment, discussed in the context of the policy-making process in Norway, including ethical and legislational considerations. METHODS: Clinical gene therapy protocols, ongoing or completed with published results, where available, were identified through a systematic survey of descriptive protocols and publications. Preclinical literature was also reviewed. RESULTS: Gene therapy is dominated by preclinical and clinical research. Most of the gene therapy protocols identified are in early phases (phases I and II) with only a few patients in each study. Of the protocols included in the assessment, only three phase III studies are represented. Except for the use of soluble antisense oligonucleotides against cytomegalovirus eye infection, gene therapy is presently not an established treatment modality. Promising results have been observed in treatment of cancer and cardiovascular diseases and, most recently, in inherited severe combined immunodeficiency and hemophilia. Several interesting principles addressing a large panel of conditions are currently being developed and tested. CONCLUSIONS: Gene therapy is developing into an important medical concept that needs to be included within the Norwegian healthcare system. It is recommended that the Norwegian Ministry of Health and Social Affairs fund a national program to boost infrastructure in selected scientific groups both in preclinical and clinical research. The national procedures regulating approval of gene therapy trials should be made more efficient while at the same time allowing for proper control and ethical considerations. It is emphasized that gene therapy trials should be carefully monitored for side effects.