Note from the National Guideline Clearinghouse (NGC): The National Institute for Health and Clinical Excellence (NICE) commissioned an independent academic centre to perform a systematic literature review on the technology considered in this appraisal and prepare an assessment report. The assessment report for this technology appraisal was prepared by the Southampton Health Technology Assessment Centre (SHTAC), University of Southampton. (See the "Availability of Companion Documents" field.)
Clinical Effectiveness
Critique of Manufacturer's Approach
Description of Manufacturer's Search Strategy
The manufacturer's search contains some omissions, however it is thought unlikely to affect the identification of key studies. Most of the searches have been taken from a previous Technology Assessment Report (TAR) for the NICE appraisal of etanercept and efalizumab.
The manufacturer has adhered to the minimum database search criteria as specified by NICE, (Medline, Embase, Medline in Progress [MEIP] and Cochrane) when undertaking clinical effectiveness searches.
The manufacturer stated that "a search of MEIP was conducted but was not considered applicable since none of the papers in this database fit the inclusion criteria". There is no record of additional searching having been undertaken on other databases, and it is not stated if the searches were restricted to English language.
The date that the clinical searches were undertaken was not recorded in the manufacturer's submission (MS).
The search terms selected by the manufacturer included appropriate descriptor and free text terms (the latter were adequately truncated). The documented strategies were appropriately run on the specified databases. An acceptable randomised controlled trial (RCT) filter was applied to the search strategy. The numbers from each search line have not been recorded in the MS.
The searches for the clinical review included systematic reviews, but in practice the procedure of scanning reference lists was only carried out for a single review, as it was the only relevant systematic review identified.
The ERG re-ran searches in Medline and Ovid with an arbitrary date selection of 1996-2007 and the numbers retrieved were similar to those of the manufacturer.
It is noted in the MS that there are no relevant ongoing RCTs. However the search for ongoing trials was not recorded in the MS. For example, there is no mention of using datasets such as National Research Register or Clinical Trials.gov. There is no record of searching for papers presented at key conferences or symposia.
Statement of the Inclusion/Exclusion Criteria Used in the Study Selection and Comment on Whether They Were Appropriate
The MS specified the following inclusion criteria for the systematic review of the literature:
- RCTs of infliximab efficacy were selected as relevant if they were placebo-controlled, with randomised and double-blinded allocation to study arms. Baseline matching of key patient characteristics was also required: namely age, sex, as well as treatment and disease history. It was necessary that patients in all studies had active psoriasis at time of study entry, to be relevant to infliximab's licensed indication.
- It was also required that the studies had as their primary, or co-primary, endpoint a relevant psoriasis severity score such as the Psoriasis Area and Severity Index (PASI).
The specified inclusion/exclusion criteria were appropriate and largely reflect the information given in the decision problem. However:
- The MS does not report any inclusion criteria relating to the comparator treatments etanercept and efalizumab.
- The MS does not specify dose as an inclusion criteria and may therefore include patients not reflective of United Kingdom (UK) clinical practice.
- The MS provides no criteria for the rating of severity of psoriasis to ensure patients were moderate-to-severe.
- There was no description of what would constitute a failure to respond, or intolerance/contraindication, to prior systemic treatments, as per the NICE scope. The ERG clinical advisor suggests that most patients entering trials for biologics will have failed other treatments in a clinical setting or been contraindicated according to what co-morbidities they had.
- Baseline matching on certain patient demographics was an additional requirement for inclusion.
- The MS does not state clearly whether conference abstracts would be included or excluded. The ERG requested clarification from the manufacturer about the inclusion/exclusion of these types of publications. The manufacturer noted in their response that these were not eligible for inclusion. However, one conference proceeding was included for the comparator interventions (refer to Table 2 in the ERG Report [See the "Availability of Companion Documents" field].)
- The MS state that they applied the same criteria to the selection of RCTs of competitor products etanercept and efalizumab. A flow chart of included and excluded studies of these comparator interventions was not provided.
Refer to sections 3.1.1 and 3.1.2 of the ERG Report (see the "Availability of Companion Documents" field) for more information on clinical effectiveness searches.
Cost-Effectiveness
Critique of Manufacturer's Approach
Cost-Effectiveness Searches
The cost-effectiveness searches of the manufacturer exceed the minimum database criteria set by NICE (Medline, Embase, MEIP, National Health Service Economic Evaluation Database [NHS EED] and Health Economic Evaluations Database [HEED]). The manufacturer has additionally searched Biosis, Derwent Drug file, Current Content/clinical medicine, and Pubmed. MEIP per se is not documented as being searched although Pubmed would have been a good substitute. It is unusual to select Biosis and Derwent Drug File for cost effectiveness searches. However, this is unlikely to have impacted in a negative way on the searches.
The date for the economic searches is recorded in the MS as taking place on April 26th 2007 spanning 2004-2007 which is a limited period. It was not stated that this was an update search.
The cost effectiveness search strategy is presented primarily as a list of terms. There is no syntax to indicate which items are descriptors and which items were applied to the strategy in free text. The MS also only provides one listing for all the databases searched. However, the descriptor terms would differ in the various databases. Consequently each database strategy should have been displayed separately as per the clinical effectiveness search strategy. There is no evidence of using exploded terms for descriptors nor for using truncation for free text.
The ERG requested further clarification over the cost effectiveness search strategy and this can be found in Appendix 1 of the ERG Report (see the "Availability of Companion Documents" field). This "revised" strategy is appropriately documented and contains a cost filter. For the sake of consistency, the term psoriasis/ could have been exploded (exp psoriasis/) to match with the search strategy in the clinical effectiveness searches.
Refer to section 3.1.1.2 of the ERG Report (see the "Availability of Companion Documents" field) for more information on cost-effectiveness searches.
