Psoriasis - adalimumab: appraisal consultation document
Adalimumab for the treatment of adults with psoriasis
The Department of Health has asked the National Institute for Health and Clinical Excellence (NICE or the Institute) to conduct a single technology appraisal (STA) of adalimumab for the treatment of adults with psoriasis and provide guidance on its use to the NHS in England and Wales. The Appraisal Committee has had its first meeting to consider both the evidence submitted by the manufacturer and the views put forward by non-manufacturer consultees and commentators, and by the clinical specialist and patient expert representatives nominated for this appraisal by non-manufacturer consultees and commentators. The Committee has developed preliminary recommendations on the use of adalimumab for the treatment of adults with psoriasis.
This document has been prepared for consultation with the formal consultees. It summarises the evidence and views that have been considered and sets out the preliminary recommendations developed by the Committee. The Institute is now inviting comments from the formal consultees in the appraisal process (the consultees for this appraisal are listed on the NICE website, www.nice.org.uk). This document should be read in conjunction with the evidence base for this appraisal (the evaluation report) which is available from www.nice.org.uk
Note that this document does not constitute the Institute's formal guidance on this technology. The recommendations made in section 1 are preliminary and may change after consultation .
The process the Institute will follow after the consultation period is summarised below. For further details, see the 'Guide to the single technology appraisal process' (this document is available on the Institute's website, www.nice.org.uk).
The Appraisal Committee will meet again to consider the original evidence and this appraisal consultation document in the light of the views of the formal consultees.
At that meeting, the Committee will also consider comments made on the document by people who are not formal consultees in the appraisal process.
After considering feedback from the consultation process, the Committee will prepare the final appraisal determination (FAD) and submit it to the Institute.
Subject to any appeal by consultees, the FAD may be used as the basis for the Institute's guidance on the use of the appraised technology in the NHS in England and Wales.
The key dates for this appraisal are:
Closing date for comments: 21 February 2008
Second Appraisal Committee meeting: 6 March 2008
Details of membership of the Appraisal Committee are given in appendix A, and a list of the sources of evidence used in the preparation of this document is given in appendix B.
Note that this document does not constitute the Institute's formal guidance on this technology. The recommendations made in Section 1 are preliminary and may change after consultation.
| 1 | Appraisal Committee's preliminary recommendations |
| 1.1 |
Adalimumab is recommended as a treatment option for adults with plaque psoriasis in whom anti-tumour necrosis factor (TNF) treatment is being considered and when the following criteria are both met. The disease is severe as defined by a total Psoriasis Area Severity Index (PASI) of 10 or more and a Dermatology Life Quality Index (DLQI) of more than 10. The psoriasis has not responded to standard systemic therapies including ciclosporin, methotrexate and PUVA (psoralen and long-wave ultraviolet radiation); or the person is intolerant to, or has a contraindication to, these treatments. |
| 1.2 |
It is recommended that adalimumab is discontinued in people whose psoriasis has not responded adequately at 12 weeks. An adequate response is defined as either:
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| 1.3 | It is recommended that, when using the DLQI, healthcare professionals take care to ensure that a person's disabilities (such as physical impairments) and linguistic or other communication difficulties are taken into account when reaching conclusions on the severity of plaque psoriasis. In such cases, healthcare professionals should ensure that their use of the DLQI continues to be a sufficiently accurate measure. The same approach should apply in the context of a decision about whether to continue the use of the drug in accordance with section 1.2. |
| 2 | The technology |
| 2.1 | Adalimumab (Humira, Abbott Laboratories) is a recombinant human monoclonal antibody that binds specifically to TNF-α, blocking interaction with its cell-surface receptors and thereby limiting the promotion of inflammatory pathways. It is indicated for the treatment of moderate to severe chronic plaque psoriasis in adult patients who failed to respond to or who have a contraindication to, or are intolerant to other systemic therapy including ciclosporin, methotrexate or psoralen and long-wave ultraviolet radiation (PUVA). The recommended dosage for adalimumab is an 80 mg loading dose administered by subcutaneous injection at baseline, followed by 40 mg every other week from week 1. Adalimumab is available in two presentations: a prefilled syringe and an autoinjection pen. For further information, see the summary of product characteristics (SPC). |
| 2.2 | Common adverse events associated with adalimumab, as specified in the SPC, include injection site reactions, infections, dizziness, headache, diarrhoea, abdominal pain, stomatitis and mouth ulceration, nausea, increased hepatic enzymes, musculoskeletal pain and fatigue. Contraindications listed in the SPC include active tuberculosis or other severe infections such as sepsis, opportunistic infections and moderate to severe heart failure. For full details of side effects and contraindications, see the SPC. |
| 2.3 | Adalimumab costs £357.50 per 40 mg prefilled syringe (excluding VAT; 'British national formulary' [BNF] edition 54). The manufacturer states that the autoinjection pen (containing 40 mg of adalimumab) also costs £357.50 per injection; however this presentation is not listed in the current BNF (edition 54). The average annual cost per patient of adalimumab is estimated by the manufacturer to be £9652.50 in the first year and £9295 in subsequent years. Costs may vary in different settings because of negotiated procurement discounts. |
| 3 | The manufacturer's submission |
| The Appraisal Committee (appendix A) considered evidence submitted by the manufacturer of adalimumab and a review of this submission by the Evidence Review Group (ERG; appendix B). | |
| 3.1 | In its submission, the manufacturer compared adalimumab with etanercept, efalizumab, infliximab, methotrexate, ciclosporin and supportive care. Results are not presented below for comparisons with methotrexate or ciclosporin, to reflect the licensed use of adalimumab. |
| 3.2 | The major clinical outcome examined was improvement in PASI score, a measure of disease severity based on body surface area affected and the extent, scaliness, thickness and redness of plaques, with scores ranging from 0 to 72. The DLQI score was also used in the manufacturer's submission. This is a disease-specific quality of life measure with scores ranging from 0 to 30. |
| 3.3 |
The main evidence on efficacy in the manufacturer's submission was derived from three randomised controlled trials (RCTs):
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| 3.4 | The results of the three RCTs showed that a statistically significantly larger proportion of people treated with adalimumab at its licensed dose experienced a 75% or higher improvement in PASI score (PASI 75; a primary endpoint in the trials) compared with those who received placebo. The proportions of people with at least a PASI 75 response, relative to baseline, for adalimumab compared with placebo were: 53% versus 4% (M02-528, 12 weeks); 71% versus 7% (REVEAL, 16 weeks); and 80% versus 19%, respectively (CHAMPION, 16 weeks); p < 0.001 in all comparisons. |
| 3.5 | Longer term data from the REVEAL trial showed that PASI response was maintained and continued to favour adalimumab over placebo. During the open-label period of the trial, 89% of people originally randomised to adalimumab had at least a PASI 75 response at week 33. In people originally randomised to placebo, PASI 90 response rates increased from week 16 to weeks 24 and 33. During the re-randomisation period of the trial (week 33 to week 52), the proportion of people for whom an adequate response was lost (a primary outcome of the trial) was statistically significantly higher for people re-randomised to placebo (28%) compared with people re-randomised to adalimumab (5%) (between-group difference -23.5%; 95% confidence interval [CI] -16.9 to -30.2; p < 0.001). |
| 3.6 | For secondary outcomes recorded in the trials, such as the physician's global assessment (PGA) score, the DLQI score and other health-related quality of life scores, adalimumab demonstrated statistically significant improvements compared with placebo. |
| 3.7 | Adalimumab was generally safe and well tolerated. Data from the placebo-controlled study set (n = 1469) show that the incidence of adverse events that might be related to the study drug was statistically significantly higher in the adalimumab treatment group than in the placebo treatment group. The most commonly reported adverse effects in people treated with adalimumab were nasopharyngitis, upper respiratory tract infection and headache. The incidence of severe adverse events was low and comparable in the adalimumab and placebo treatment groups. |
| 3.8 | The manufacturer carried out an indirect comparison of adalimumab with etanercept, efalizumab, infliximab, ciclosporin and methotrexate using a mixed-treatment comparison approach within a Bayesian evidence synthesis framework. The approach compared each treatment through common links to placebo, either by means of direct comparison or through comparison with any other active agent compared with placebo. The manufacturer included data from the three adalimumab RCTs described in section 3.3, four RCTs comparing etanercept with placebo, four comparing infliximab with placebo, five comparing efalizumab with placebo, one comparing ciclosporin with placebo and one comparing methotrexate with ciclosporin. The results from the evidence synthesis showed that the mean probability of achieving a PASI 75 response was 67% for adalimumab (95% CI, 57 to 74), 81% for infliximab (95% CI 75 to 87), 38% for etanercept 25 mg (the dose recommended by NICE; 95% CI 29 to 47), 29% for efalizumab (95% CI, 24 to 35) and 5% for supportive care (95% CI, 4 to 6). |
| 3.9 | The manufacturer based its cost-effectiveness analysis on the York model used in the NICE appraisal of etanercept and efalizumab for the treatment of adults with psoriasis, NICE technology appraisal guidance 103 (TA 103). The model was adapted by the manufacturer of adalimumab to incorporate additional evidence, including the results of the mixed-treatment comparison described in section 3.6. The updated model also included new utility data derived from empirical estimates of the relationship between PASI response rates and changes in EQ-5D from the CHAMPION study and study M02-528. |
| 3.10 | Within the model, each person underwent a preliminary period of treatment after which initial response was assessed (this was referred to as the trial period). Continuation of therapy into the next phase (referred to as the treatment period) only occurred if a PASI 75 response was achieved in the trial period. The respective European marketing authorisations defined the time at which response was measured. These time points were 12 weeks (etanercept, efalizumab), 14 weeks (infliximab) and 16 weeks (adalimumab). The treatment period for each therapy (following a response) was taken from the York model, estimated using an annual drop-out rate of 20% for all patients. The cost and resource use data were taken from the York model, NHS Reference Costs and National Tariff and the BNF edition 53. The Personal Social Services Research Unit (PSSRU) inflation index was used to update costs to 2005-06, if current costs were not available. |
| 3.11 | In the manufacturer's base-case analysis, the incremental cost per quality-adjusted life year (QALY) gained for adalimumab compared with supportive care was £30,500. Etanercept given continuously was dominated by adalimumab (that is, etanercept had higher costs and lower effectiveness than adalimumab), and etanercept given intermittently (assumed to be 88% of the dose of continuous etanercept) and efalizumab were ruled out on the grounds of extended domination (that is, the incremental costs per QALY gained were higher than for adalimumab even though either the cost or effectiveness was more favourable). |
| 3.12 | The manufacturer's base-case analysis only included people whose psoriasis had a substantial effect on their quality of life, as indicated by a DLQI score greater than 10. The manufacturer conducted a sensitivity analysis for people with milder forms of psoriasis (DLQI less than or equal to 10) and this increased the incremental cost per QALY gained for adalimumab compared with supportive care from £30,500 (DLQI greater than 10) to £80,100 (DLQI less than or equal to 10). |
| 3.13 | The manufacturer carried out further sensitivity analyses to test key assumptions in the model. Changing the number of hospital inpatient days assumed to be avoided by using a biological therapy instead of supportive care had a large impact on the results. Changing the assumption used in the base-case analysis (21 hospital inpatient days avoided per year) to 0 days and 39 days was associated with incremental costs per QALY gained of £60,600 and £4800, respectively, compared with supportive care. |
| 3.14 | Changing the assumption regarding the dose for intermittent etanercept from 88% of the dose of continuous etanercept to 74% (the figure used in the York model) reduced the incremental cost per QALY gained for intermittent etanercept compared with supportive care from £37,300 to £27,600. |
| 3.15 | The manufacturer also carried out a probabilistic sensitivity analysis. This estimated that adalimumab had a 46% probability of being cost effective at a threshold of £30,000 per QALY gained. |
| 3.16 | The ERG considered there to be a number of limitations with the evidence in the manufacturer's submission. It noted that very limited descriptions of the comparator trials and the methodological assumptions used in the mixed-treatment comparison were provided by the manufacturer. It was also uncertain about the appropriateness of the mixed-treatment comparison because the manufacturer did not discuss the issue of possible heterogeneity across the trials. The ERG did however state that the results for most of the included treatments were broadly similar to those published by the York Assessment Group in their analysis of etanercept and efalizumab (TA 103). |
| 3.17 | The ERG also commented that it is uncertain to what extent the trial populations included in the adalimumab and comparator trials match the population specified in the decision problem, in terms of prior treatment with systemic therapy. |
| 3.18 | The ERG identified a number of limitations with the manufacturer's model. Because of the limited information provided, the ERG was unclear about the appropriateness of the approach used by the manufacturer to relate changes in PASI scores to EQ-5D data. |
| 3.19 | The ERG pointed out the paucity of information available on the number of hospital inpatient days that are avoided by use of biological therapy instead of supportive care and that changes to the assumption used in the manufacturer's model (21 days per year) had a large impact on the results for all the biological drugs. The ERG also commented that the baseline DLQI of people was important in determining the cost-effectiveness results (see section 3.10). |
| 3.20 | The ERG was concerned that the manufacturer's base-case assumptions for intermittent etanercept did not seem appropriate, in particular that the dose of intermittent therapy used in the model (88% of continuous therapy) to calculate costs was inconsistent with the dose used to calculate utility gains (68%). |
| 3.21 | The ERG re-ran the manufacturer's analysis changing the assumption for the dose of intermittent etanercept to the value used in the York model (74% of the continuous etanercept dose). In this analysis the incremental cost per QALY gained of adalimumab compared with intermittent etanercept was £36,700. |
| 3.22 | Full details of all the evidence are in the manufacturer's submission and the ERG report, which are available from www.nice.org.uk |
| 4 | Consideration of the evidence |
| 4.1 | The Appraisal Committee reviewed the data available on the clinical and cost effectiveness of adalimumab for the treatment of psoriasis in adults, having considered evidence on the nature of the condition and the value placed on the benefits of adalimumab by people with psoriasis, those who represent them, and clinical specialists. It was also mindful of the need to take account of the effective use of NHS resources. |
| 4.2 | The Committee considered that the RCTs identified in the manufacturer's submission demonstrated the clinical effectiveness of adalimumab compared with placebo in people with moderate to severe plaque psoriasis. The Committee, however, also noted that the inclusion criteria for the studies did not fully reflect the population for which this technology is licensed because the psoriasis of the participants in the trials had not necessarily failed to respond to systemic therapies. However, the Committee was reassured by the views of the clinical experts that adalimumab is as effective for people who have not responded to other available treatments as for those who are otherwise treatment naive. |
| 4.3 | The Committee noted that there are no head-to-head studies comparing adalimumab with the current standard treatment for people who have not responded to systemic therapies, in particular other biological treatments that are used in UK clinical practice as per NICE guidance on etanercept and efalizumab (TA 103). The Committee heard from the clinical experts that, based on clinical experience, adalimumab could provide greater clinical benefit than etanercept when an anti-TNF is considered appropriate for treatment in a person with severe psoriasis. The Committee also noted the results of the mixed-treatment comparison conducted by the manufacturer, which suggested a higher probability of response following treatment with adalimumab compared with etanercept. It was aware however that the ERG had expressed concerns with this analysis and that the robustness of the results was uncertain. For example, very limited descriptions of the comparator trials and the methodological assumptions used in the mixed-treatment comparison were provided by the manufacturer, and the issue of possible heterogeneity across the trials was not discussed. Therefore, the Committee was persuaded that, although there is some evidence to suggest that adalimumab may be more effective than etanercept, clinical superiority of adalimumab over etanercept has not been firmly established in the treatment of severe psoriasis. |
| 4.4 | The Committee heard from the clinical experts and patient representatives that adalimumab is generally easier to use than etanercept because of the self-injection dosing regimen every other week. |
| 4.5 | The Committee discussed the results of the economic analysis conducted by the manufacturer. It considered that the overall approach adopted by the manufacturer was appropriate but that there was considerable uncertainty in the estimates of cost effectiveness that had been produced. A crucial assumption in the model is that 21 hospital inpatient days are avoided by use of a biological therapy as compared with the use of supportive care in the absence of biological therapy. The Committee noted the paucity of data available to inform this assumption. It heard from the clinical experts that 21 days of inpatient treatment in the absence of biological therapy for this group of people with severe psoriasis is an appropriate estimate and that recently published, multicentre audit data support this. The Committee was also aware that this assumption had been accepted in the NICE appraisal of etanercept and efalizumab for the treatment of adults with psoriasis (TA 103) and, in the absence of any strong evidence to the contrary, agreed that this represented the most appropriate estimate. |
| 4.6 | The Committee noted that in the manufacturer's base-case analysis using indirect comparisons, etanercept given continuously was dominated by adalimumab (that is, etanercept had higher costs and lower effectiveness) and etanercept given intermittently (assumed to be 88% of the dose of continuous etanercept) was ruled out on the grounds of extended domination (that is, the incremental cost per QALY gained was higher even though either the cost or effectiveness was more favourable). The Committee noted that assumptions regarding the dose for intermittent etanercept had a large impact on the results. When the ERG re-ran the analysis using the assumption used in the York model, as per TA 103 (intermittent etanercept assumed to be 74% of the continuous etanercept dose), the incremental cost per QALY gained of adalimumab compared with intermittent etanercept was £36,700. The Committee was also concerned that, in the manufacturer's analysis, the dose of intermittent therapy used to calculate costs (88% of continuous therapy) was inconsistent with the dose used to estimate utility gains (68% of continuous therapy). Therefore, the Committee agreed that the ERG's analysis represented the most appropriate analysis on which to base its decision regarding the use of adalimumab. |
| 4.7 | The Committee considered whether the appropriate comparator for adalimumab should be etanercept given continuously or given intermittently in line with NICE technology appraisal guidance 103. It heard from the clinical experts that people with severe disease are either not treated with intermittent therapy or have a very small gap (not usually more than 1 week) between courses of treatment because the disease flares up very quickly. The Committee was therefore persuaded that, for some people with severe psoriasis, the periods of time between courses of intermittent treatment with etanercept could often be very short. The Committee agreed that, for people with severe psoriasis, the true incremental cost per QALY gained for adalimumab compared with etanercept would take into account the results calculated by the ERG for both intermittent etanercept and continuous etanercept and would be likely to fall within a range consistent with that which had previously been considered a cost-effective use of NHS resources. |
| 4.8 | The Committee was aware that the manufacturer's base-case analysis (and the ERG's re-analysis of this described in section 4.6) only included people whose psoriasis had a substantial effect on their quality of life, as indicated by a DLQI score greater than 10. The Committee noted that the manufacturer had conducted a sensitivity analysis for people with milder forms of psoriasis (DLQI less than or equal to 10) and that this increased the incremental cost per QALY gained for adalimumab compared with supportive care from £30,500 (DLQI greater than 10) to £80,100 (DLQI less than or equal to 10). The Committee therefore agreed that it would not be cost effective to treat people who have moderate disease with adalimumab. |
| 4.9 | The Committee discussed the comparisons drawn in the manufacturer's submission between adalimumab and etanercept (used either intermittently or on a continuous basis). The Committee considered the various cost-effectiveness analyses, the critique of the ERG and the input of the clinical experts. The Committee further discussed the clinical scenario when the use of an anti-TNF is considered appropriate in the management of psoriasis. The Committee considered whether the evidence before them supported the preferential use of adalimumab over etanercept or whether it should be reserved for use when a person's psoriasis has not responded to etanercept or a person is intolerant to etanercept. Because of the limitations of the comparative clinical effectiveness data and the consequent uncertainty around the cost-effectiveness results, the Committee considered that it could not recommend adalimumab in preference to etanercept and that clinicians would need to exercise their clinical judgement in choosing between the two treatments. The Committee therefore concluded that adalimumab should be recommended as a treatment option alongside etanercept and only for people with severe disease whose psoriasis has not responded to standard systemic therapies and when initiation of the use of an anti-TNF is being considered. |
| 4.10 | The Committee considered how the population with severe psoriasis could be defined. It heard from the clinical experts that a combination of DLQI and PASI is routinely used in clinical practice and agreed that it would be appropriate to define severe disease as a PASI of 10 or more and a DLQI of more than 10 in line with the NICE guidance on etanercept and efalizumab (TA 103). |
| 4.11 | The Committee considered the appropriate duration of treatment. It noted that the principal endpoint in the adalimumab trials was a PASI 75 response at 16 weeks. However, it accepted the views of the clinical experts that it would be appropriate to assess response to treatment at 12 weeks. To ensure consistency with the NICE guidance on etanercept and efalizumab (TA 103), the Committee concluded that it would be appropriate for treatment to be continued beyond 12 weeks only in people whose psoriasis had shown a PASI 75 response to treatment within 12 weeks. In addition, the Committee agreed that the response criteria should be defined in a similar way to TA 103 and should include an additional alternative criterion of a 50% reduction in the PASI score and a five-point reduction in the DLQI. |
| 4.12 | The Committee was aware that there may be some circumstances when the DLQI is not a clinically appropriate tool to inform a clinician's conclusion on the severity of plaque psoriasis, for example, because of a person's disabilities (such as physical impairments) or linguistic or other communication difficulties. The Committee concluded that in such cases healthcare professionals should ensure that their use of the DLQI continues to be a sufficiently accurate measure. The same approach should apply in the context of a decision about whether to continue the use of adalimumab. |
| 5 | Implementation |
| 5.1 | The Healthcare Commission assesses the performance of NHS organisations in meeting core and developmental standards set by the Department of Health in 'Standards for better health' issued in July 2004. The Secretary of State has directed that the NHS provides funding and resources for medicines and treatments that have been recommended by NICE technology appraisals normally within 3 months from the date that NICE publishes the guidance. Core standard C5 states that healthcare organisations should ensure they conform to NICE technology appraisals. |
| 5.2 | 'Healthcare Standards for Wales' was issued by the Welsh Assembly Government in May 2005 and provides a framework both for self-assessment by healthcare organisations and for external review and investigation by Healthcare Inspectorate Wales. Standard 12a requires healthcare organisations to ensure that patients and service users are provided with effective treatment and care that conforms to NICE technology appraisal guidance. The Assembly Minister for Health and Social Services issued a Direction in October 2003 which requires Local Health Boards and NHS Trusts to make funding available to enable the implementation of NICE technology appraisal guidance, normally within 3 months. |
| 5.3 | NICE has developed tools to help organisations implement this guidance (listed below). These are available on our website (www.nice.org.uk/TAXXX). [Note: tools will be available when the final guidance is issued] |
| 6 | Proposed recommendations for further research |
| 6.1 | The Committee recommends that further research should be conducted comparing available anti-TNF agents (such as adalimumab, etanercept and infliximab) with each other. |
| 7 | Related NICE guidance |
| 7.1 |
Related NICE guidance:
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| 8 | Proposed date for review of guidance |
| 8.1 | The review date for a technology appraisal refers to the month and year in which the Guidance Executive will consider whether the technology should be reviewed. This decision will be taken in the light of information gathered by the Institute, and in consultation with consultees and commentators. |
| 8.2 | It is proposed that the guidance on this technology is considered for review in June 2011. The Institute would particularly welcome comment on this proposed date. |
| David Barnett |
| Chair, Appraisal Committee |
| January 2008 |
| Appendix A. Appraisal Committee members and NICE project team |
| A Appraisal Committee members |
| The Appraisal Committee is a standing advisory committee of the Institute. Its members are appointed for a 3-year term. A list of the Committee members who took part in the discussions for this appraisal appears below. The Appraisal Committee meets three times a month except in December, when there are no meetings. The Committee membership is split into three branches, each with a chair and vice chair. Each branch considers its own list of technologies, and ongoing topics are not moved between the branches. |
| Committee members are asked to declare any interests in the technology to be appraised. If it is considered there is a conflict of interest, the member is excluded from participating further in that appraisal. |
| The minutes of each Appraisal Committee meeting, which include the names of the members who attended and their declarations of interests, are posted on the NICE website. |
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Professor Keith Abrams Dr Darren Ashcroft Professor David Barnett (Chair) Professor Stirling Bryan Dr Mark Charkravarty Professor Jack Dowie Ms Lynn Field Professor Gary McVeigh Dr Neil Milner Dr Rubin Minhas Dr Rosalind Ramsay Dr Stephen Saltissi Dr Lindsay Smith Mr Roderick Smith Mr Cliff Snelling Professor Ken Stein (Chair) Professor Andrew Stevens |
| B NICE project team |
| Each technology appraisal is assigned to a team consisting of one or more health technology analysts (who act as technical leads for the appraisal), a technical adviser and a project manager. |
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Zoe Charles Elisabeth George Natalie Bemrose |
| Appendix B. Sources of evidence considered by the Committee | |
| A |
The Evidence Review Group (ERG) report for this appraisal was prepared by Southampton Health Technology Assessments Centre (SHTAC), University of Southampton:
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| B | The following organisations accepted the invitation to participate in this appraisal. They were invited to comment on the draft scope, the ERG report and the appraisal consultation document (ACD). Organisations listed in I were also invited to make written submissions. Organisations listed in II gave their expert views on adalimumab by providing a written statement to the Committee. Organisations listed in I and II have the opportunity to appeal against the final appraisal determination. |
| I |
Manufacturer/sponsor:
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| II |
Professional/specialist, patient/carer groups and other organisations:
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| III |
Commentator organisations (did not provide written evidence and without the right of appeal) :
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| C |
The following individuals were selected from clinical specialist and patient advocate nominations from the non-manufacturer/sponsor consultees and commentators. They gave their expert personal view on adalimumab by attending the initial Committee discussion and providing written evidence to the Committee. They are invited to comment on the ACD.
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