Photodynamic therapy with verteporfin for macular degeneration

Use of a structured format No Abstract No Abstract No Abstract Explicit description of clinical question Description of databases and other information sources Description of selection criteria Description of methods for validity assessment Description of methods for data abstraction Description of study characteristics Description of quantitative data synthesis Description of characteristics of included and excluded studies Description of quantitative findings Description of qualitative findings Description of results of subgroup analysis Introduction Explicit description of clinical problem Explicit description of biological rationale for intervention Explicit description of rationale for review Methods Detailed description of information sources Detailed description of restrictions on searching Description of inclusion and exclusion criteria Description of criteria and process used for validity assessment Description of processes used for data abstraction Description of study characteristics included Description of methods of assessment of clinical heterogeneity Description of principal measures of effect Description of methods of combining results N/A N/A N/A N/A N/A N/A Description of methods used to handle missing data Description of methods of assessment of statistical heterogeneity N/A N/A N/A N/A N/A N/A Description of rationale for a priori sensitivity testing and subgroup analysis Description of methods to assess publication bias Results Description of profile of trial flow Presentation of descriptive data for each trial Report of agreement on the selection of studies Report of agreement on validity assessment Presentation of simple summary results Presentation of data needed to calculate effect sizes and confidence intervals Discussion Summarisation of key findings Discussion of clinical inferences based on internal and external validity Interpretation of the results in the light of the totality of available evidence Description of potential biases in the review process Suggestions for future research agenda * NHSC — National Horizon Scanning Centre 2000; AHFMR — Alberta Heritage Foundation for Medical Research 2000; HCFA — Health Care Financing Administration — Tunis et al. 2000; SMM — Norwegian Centre for Health Technology Assessment 2000; AAO — American Academy of Ophthalmology — Fong 2000; Cochrane — Wormald et al. 2001 Overall, the reviews rated poorly against the QUOROM checklist (Table 15). The Cochrane systematic review (Wormald et al. 2000) met the most criteria in the QUOROM checklist followed by the American Academy of Ophthalmology review (Fong 2000). Three reviews (National Horizon Scanning Centre 2000, Alberta Heritage Foundation for Medical Research 2000, Tunis et al. 2000) did not include an abstract and this contributed to their relative poor ratings against the QUOROM checklist. As a one dimensional instrument, QUOROM has some limitations as an assessment tool and in some cases may mislead. For example, the Cochrane systematic review (Wormald et al. 2000) does not identify itself as a systematic review in the title although, by virtue of the fact that it is a Cochrane review, is systematic and this is not reflected in the QUOROM checklist. As the QUOROM checklist is a nominal scale simply reflecting the reporting of systematic reviews, an assessment of the reviews against qualitative criteria (Chalmers & Altman 1995, Greenhalgh 1997, Sackett et al. 2000) was also used to add another dimension to the assessment of the validity of systematic reviews. The Cochrane systematic review (Wormald et al. 2000) was the only one to thoroughly fulfil all the criteria. Although the remaining reviews varied in their validity, all reported on the TAP study group randomised controlled trials. A synopsis of the assessment of the reviews against relevant qualitative criteria follows. Focused question The Cochrane review (Wormald et al. 2000) provided a focused review, giving an explicit statement of the patient group (neovascular MD), intervention (PDT) and outcomes (prevention of visual loss, new vessel growth, quality of life, adverse events) that were the focus of the review. The National Horizon Scanning Centre (2000) and the Health Care Financing Administration (Tunis et al. 2000) reviews provided statements of the patient group and intervention that were the focus of the review. The National Horizon Scanning Centre (2000) specifically limited their review to patients with classic or partially classic choroidal neovascularisation in MD, and the intervention was PDT with verteporfin or tin ethyl etiopurpurin (SnET2). Tunis et al. (2000) focused their review on the treatment of patients with neovascular MD using PDT with verteporfin. Fong (2000) and the Alberta Heritage Foundation for Medical Research (2000) also explicitly stated their questions of interest while the Norwegian Centre for Health Technology Assessment (2000) did not specify a question. Inclusion and exclusion criteria This criterion addresses whether the review provided explicit a priori details of the studies that were to be included in and excluded from the review. The Cochrane review (Wormald et al. 2000) was the only one that fulfilled this criterion, stating that only randomised controlled trials examining the effectiveness of PDT in patients with neovascular MD would be included in the review. Any other study designs, patient groups or interventions were to be excluded. Explicit comprehensive search strategy This criterion addresses whether the review incorporated a search strategy comprehensive enough that it was unlikely to have missed studies. The Cochrane review provided the most thorough and explicit search strategy of all the reviews. The authors searched several databases without any language restrictions as well as a specialised register of the Cochrane Collaboration ensuring substantial effort was made to retrieve unpublished, ‘grey’ literature. Thus it is likely that publication bias was minimised as much as possible in this review. Fong (2000), Alberta Heritage Foundation for Medical Research (2000) and Tunis et al. (2000) described limited search strategies. Fong (2000) searched Medline from 1999 to 2000, but also attempted to uncover unpublished literature by contacting ophthalmology organisations and industry. Contracts were not explicitly stated. Tunis et al. (2000) also searched Medline/Pubmed and contacted unspecified ‘experts’ while the Alberta Heritage Foundation for Medical Research (2000) contacted the United States Food and Drug Administration to attempt to uncover other literature. A search strategy was not described in the reviews by the Norwegian Centre for Health Technology Assessment (2000), and the National Horizon Scanning Centre (2000). Assessed validity of included trials The Cochrane review (Wormald et al. 2000) and the Health Care Financing Administration review (Tunis et al. 2000) thoroughly and explicitly assessed the validity of their included trials. The American Academy of Ophthalmology review (Fong 2000) and the Alberta Heritage Foundation for Medical Research (2000) stated that included trials were of high quality but did not explicitly describe how they assessed them. The remaining reviews did not state if they assessed the validity of included trials. Results of systematic reviews The systematic reviews all reported results from the TAP studies. The National Horizon Scanning Centre (2000) and Cochrane (Wormald et al. 2000) reviews were completed before the publication of the two year TAP trial outcomes (TAP Study Group 2001) and thus they reported only the one year outcomes from the TAP study. The reviews from the American Academy of Ophthalmology (Fong 2000) and the Health Care Financing Administration (Tunis et al. 2000) were published after both the TAP 1 and TAP 2 reports and included a summary of both the first year and second year outcomes. The reviews from the Alberta Heritage Foundation for Medical Research (2000) and the Norwegian Centre for Health Technology Assessment (2000) reported first year results from the TAP study and preliminary results of the second year outcomes that were available in abstract form. Results of the TAP trials have already been discussed in detail and will not be repeated here. Discussion of systematic reviews The systematic review and health technology assessments conclude from the TAP trials that PDT with verteporfin is effective in retarding the loss of visual acuity in patients with predominantly classic subfoveal CNV secondary to macular degeneration. Some important issues discussed in the systematic review and health technology assessments include the following: • There is no long-term evidence (beyond two years) of the effectiveness and cost-effectiveness of PDT with verteporfin. • The effect of treatment on patient-oriented outcomes such as quality of life have not been reported in peer-reviewed literature. • Repeat treatments are required. However, the number and frequency of repeat treatments beyond two years is unknown and the safety implications are also unclear. • Diagnosis of subfoveal classic type CNV lesions is reliant on fluorescein angiography. Even trained readers find it difficult to interpret the results of this procedure, particularly in lesions that are approximately 50 per cent classic. This may lead to the use of PDT with verteporfin for patients unlikely to benefit. • The number of patients who presented for treatment in the TAP study was not stated. Thus the proportion of patients who were deemed eligible for treatment after fluorescein angiography is not clear. Verbal estimates of 5–7 per cent from one TAP member and 25 per cent from another have been reported (Wormald et al. 2000). Selection of patients for therapy A key issue identified in the systematic reviews was identifying eligible patients for this treatment. The Alberta Heritage Foundation for Medical Research (2000) has proposed the following criteria for pati