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  • Protocol
  • Open Access
  • Open Peer Review

Economic evidence for the prevention and treatment of atopic eczema: a protocol for a systematic review

  • 1Email author,
  • 1,
  • 1 and
  • 2
Systematic Reviews20165:90

  • Received: 12 January 2016
  • Accepted: 10 May 2016
  • Published:
Open Peer Review reports



Eczema, synonymous with atopic eczema or atopic dermatitis, is a chronic skin disease that has a similar impact on health-related quality of life as other chronic diseases. The proposed research aims to provide a comprehensive systematic assessment of the economic evidence base available to inform economic modelling and decision making on interventions to prevent and treat eczema at any stage of the life course. Whilst the Global Resource of Eczema Trials (GREAT) database collects together the effectiveness evidence for eczema, there is currently no such systematic resource on the economics of eczema. It is important to gain an overview of the current state of the art of economic methods in the field of eczema in order to strengthen the economic evidence base further.


The proposed study is a systematic review of the economic evidence surrounding interventions for the prevention and treatment of eczema. Relevant search terms will be used to search MEDLINE, EMBASE, Database of Abstracts of Reviews of Effects, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, National Health Service (NHS) Economic Evaluation Database, Health Technology Assessment, Cumulative Index to Nursing and Allied Health Literature, EconLit, Scopus, Cost-Effectiveness Analysis Registry and Web of Science in order to identify relevant evidence. To be eligible for inclusion studies will be primary empirical studies evaluating the cost, utility or full economic evaluation of interventions for preventing or treating eczema. Two reviewers will independently assess studies for eligibility and perform data abstraction. Evidence tables will be produced presenting details of study characteristics, costing methods, outcome methods and quality assessment. The methodological quality of studies will be assessed using accepted checklists.


The systematic review is being undertaken to identify the type of economic evidence available, summarise the results of the available economic evidence and critically appraise the quality of economic evidence currently available to inform future economic modelling and resource allocation decisions about interventions to prevent or treat eczema. We aim to use the review to offer guidance about how to gather economic evidence in studies of eczema and/or what further research is necessary in order to inform this.

Systematic review registration

PROSPERO CRD42015024633


  • Eczema
  • Economics
  • Costs
  • Health-related quality of life
  • Cost effectiveness


In the UK, the lifetime prevalence of eczema is estimated to be between 16 and 20 % making it the commonest inflammatory skin condition in children, and it has been increasing in “western style” environments [13]. In the UK, the age-sex standardised incidence and lifetime prevalence of eczema has increased between 2001 and 2005 from 9.58 per 1000 to 13.58 per 1000 patients and 77.78 per 1000 to 115.26 per 1000, respectively [4]. Up to 50 % of childhood cases will experience recurrence in adulthood [2]. Eczema is largely managed in primary care. Skin conditions are the commonest new reason patients consult their GP [5]. Eczema has been found to have a similar impact on health-related quality of life as other common childhood conditions such as asthma and diabetes [6]. Eczema impacts quality of life by causing itching, sleep loss and social stigma for the child. Families may also suffer from sleep loss and time taken off work to accompany children to health appointments [7]. The condition is associated with atopy so children with the condition are more likely to develop asthma and allergic rhinitis [8]. It is also believed that eczema has large cost implications. For instance, in 1995–1996, the total annual UK cost of eczema in children aged 5 years or younger was estimated as £47 million (£80 per child) [9]. Looking at a broader age range, the UK total annual cost was estimated to be around £465 million, of which £125 million were National Health Service (NHS) costs, £297 million costs incurred by patients and £42 million by society in terms of lost productivity (price year not reported) [10]. These UK-based estimates of the total annual UK costs of eczema are now dated, the estimates were based on small samples [146 in [10] and 1523 in [9]], and the range of treatments available has increased and is likely to increase in the future with the addition of new biologics [11].

Despite eczema being common, there remain many unknowns about how to prevent and treat the condition. The James Lind Alliance (JLA) [12] Priority Setting Partnership (PSP) on eczema illustrates this ( and [13]). The JLA facilitates disease specific PSPs that bring together patients, carers and health professionals to identify and prioritise research for the treatment uncertainties of the disease of interest ( The eczema PSP was established in 2010 with partners drawn from academic, NHS and charitable sectors and resulted in 14 treatment uncertainties being prioritised [13].

In order to draw together the effectiveness evidence of interventions for eczema, the Global Resource of Eczema Trials (GREAT) [14] database was established [15] and includes details of over 600 systematic reviews and randomised controlled trials. It does not, however, identify or bring together the economic literature on eczema, and thus, this review attempts to do this. There is likely to be less economic evidence, compared to effectiveness data, for eczema. Indeed, the English National Institute of Health and Care Excellence (NICE) has only considered economic models for two areas of eczema care: an educational intervention for those with eczema aged under 12 [16] and tacrolimus and pimecrolimus for atopic eczema [17]. It is, therefore, important to identify the current state of economic evidence addressing eczema in order to inform the design of future economic research in the area.

The proposed systematic review will address the following four research questions:
  1. 1.

    What type of health economic evidence has been used in the evaluation of the prevention and treatment of atopic eczema?

  2. 2.

    Are interventions to prevent and treat atopic eczema cost effective?

  3. 3.

    What is the quality of the health economic evidence for the prevention and treatment of atopic eczema?

  4. 4.

    What are the current gaps in the existing research?



Protocol and registration

The Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P) statement recommendations were used to develop the methods for this systematic review (see Additional file 1) and will be used in reporting the results from the study [18]. This protocol has been registered in the International Prospective Register of Systematic reviews (PROSPERO) CRD42015024633. Should protocol amendments be necessary, these will be documented including details of the date, changes made and the rationale for changes.

Literature search

The following electronic databases will be searched: MEDLINE, EMBASE, Cumulative Index to Nursing and Allied Health Literature, Cochrane Central Register of Controlled Trials, Database of Abstracts of Reviews of Effects, Cochrane Database of Systematic Reviews, NHS Economic Evaluation Database, EconLit, Scopus, Health Technology Assessment, Cost-Effectiveness Analysis Registry and Web of Science. There will be no restriction imposed on the search from date; therefore, the literature search will go from the earliest records within each database, to the single day that the search was conducted on. Search results will be downloaded to Endnote version X7 where duplicates will be identified and removed.

Reference lists of potential eligible studies, reviews, guidelines or other sources will be screened for additional literature. Authors of published abstracts and conference proceedings will be contacted by email to establish if a full paper has since been published in the grey literature.

The search strategy was guided by The Cochrane Collaboration Handbook [19] and the Centre for Reviews and Dissemination guidelines for systematic reviews [20]. Specifically, search terms used in other atopic eczema systematic reviews were used to inform the clinical search terms [21]) and were also informed by the clinical author on the paper: NL. The economic terms were similarly devised, by consulting relevant guidelines [22, 23]. The complete search strategy (with interface and coverage dates) is available in the Appendix to this protocol.

Eligible studies

A study will be included if it reports primary data on cost and/or outcome (utility or willingness to pay) data on atopic eczema. The primary interest is in full economic evaluations (cost effectiveness, cost utility, cost benefit and cost minimisation) although other partial economic evidence will also be included where the study has an explicit economic objective, this is likely to include cost-consequence analyses, cost analyses, utility assessment or willingness to pay/accept studies. There will be no restriction on the study designs used in the economic studies so, for example, economic studies conducted alongside randomised controlled trials, as part of observational studies, or as decision model-based analyses will be included. Nor will there be any restrictions on type of setting. The search was undertaken on the 9th October 2015, so only studies published before this date are included. Only full text articles published in the English language will be included, abstracts and letters will be excluded. Where two or more studies appear to be reporting on the same dataset or using the same model, the most comprehensive paper will be included unless each paper reports on a different aspect or in relation to a different jurisdiction/population (in the case of modelling studies).

Data collection

Study selection

Two independent reviewers will assess the titles and abstracts retrieved in the literature search against our inclusion criteria. In a second stage, full-text articles for those seeming to fit the criteria or where there is uncertainty about relevance will be retrieved and their eligibility assessed according to criteria set out in Table 1. Where disagreements occur a third reviewer will be involved.
Table 1

Inclusion and exclusion criteria


Inclusion criteria

Exclusion criteria


Eczema (synonyms: atopic eczema, atopic dermatitis) ICD-10 code: L20

Populations with other skin diseases other than eczema

Dyshidrotic eczema, seborrheic eczema, chronic actinic dermatitis, asteatotic eczema, allergic contact eczema, irritant contact eczema, varicose eczema, stasis eczema ICD-10 codes: L21 to L30

Study designs

Studies presenting primary data in the form of a Cost of illness, cost effectiveness, cost utility, cost benefit, cost consequences, cost analysis, utility analysis, contingent valuation

Studies without an explicit economic objective

Review articles, although the reference list for these will be checked for primary studies that should be included


Utility, QALYs, willingness to pay/accept


Publication type

Articles available in full text in English

Abstracts, letters, reviews

Data abstraction and management

Data will be extracted independently by two reviewers and entered into an electronic data extraction form developed in Microsoft Excel, with the third reviewer consulted in case of disagreements that cannot be resolved between the two reviewers. A full list of the extraction fields can be found in Table 2. The data extraction form was piloted, modified (where necessary) and reviewers’ responses calibrated on the basis of two pre-identified studies (one modelling study and one non-model-based paper). The data extracted will be analysed in a narrative/descriptive manner focusing on the methods, results and quality of studies included with the aim of identifying gaps in the evidence, areas of strength and areas in need of methodological improvement.
Table 2

Data abstraction fields

General information


 Review ID


 Author, year






 Date of review


 Publication type


Population and setting


 Type of study


 Stated type of economic analysis


 Actual type of economic analysis (if different)


 Country of study


 Study setting




 Study size


 Method of recruitment


 Recruitment time period


 Inclusion criteria


 Exclusion criteria


Study design


 Primary intervention


 Secondary intervention(s)




 Time horizon (for follow-up)




 Outcomes measure (1)


 Method of measurement (1)


 Outcome measure (2)


 Method of measurement (2)


 Outcome measure (3)


 Method of measurement (3)


 Secondary outcome measure(s)


 Method of measurement(s)


 For utility studies: what value set or direct method of measurement has been used?


 Timing of measurements


 Discount rate, outcomes


 Method of dealing with missing data—outcomes


Resource and cost information


 Cost perspective


 Intervention costs


 Direct cost items


 Method of capturing direct cost items


 Direct cost data sources


 Indirect cost items


 Method of capturing indirect cost items


 Indirect cost data sources


 Resource items collected


 Resource use, recall period


 Method of dealing with missing data—cost


 Price year




 Inflation rate, cost


 Discount rate, cost




 Resource use and costs




 Reported cost effectiveness


 Appropriateness of ICER


 Sensitivity analysis


 Major result(s)




 Funding source


Model specific information


 Type of decision analytic model


 Model perspective


 Model population


 Cohort or individual?


 Model assumptions


 Model exclusions


 Method for dividing disease severity


 Distinction between body/face eczema?


 Interventions included


 Time horizon


 Cycle length


 Value of any parameters used


 Source of parameters


 Software used for model


 Type of sensitivity analysis performed


 Method of model validation


 Author specified limitations


If the necessary data are available, the results will be discussed as subsets for different age groups (e.g. child/adult/elderly) and/or different skin disease severities and/or world regions and/or health-care settings. Furthermore, as it is expected that included studies will report results in a range of currencies, where possible, results will be reported in the original currency and price year, as well as being converted to UK pounds using the purchasing power parities provided by the Organisation for Economic Co-operation and Development (OECD), inflating to a common price year using the consumer price index, to facilitate the comparison of results across studies.

Quality assessment and data presentation

Two reviewers will independently evaluate the quality of included studies in order to assess the risk of bias. Studies will be assessed using a published checklist based on a modified version of the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) framework [24] (see Table 3). In addition, model-based economic evaluations will also be assessed using the Phillips criterion [25, 26] (see Table 4 for extraction table). Any discrepancies will be discussed and resolved by a third reviewer.
Table 3

CHEERS checklist [24]


Item no.


Reported on page/paragraph no.

Yes/no/partial/unclear/not applicable

Title and abstract



Identify the study as an economic evaluation or use more specific terms such as “cost effectiveness analysis”, and describe the interventions compared.




Provide a structured summary of objectives, perspective, setting, methods (including study design and inputs), results (including base case and uncertainty analyses), and conclusions.



Background and objectives


Provide an explicit statement of the broader context for the study. Present the study question and its relevance for health policy or practice decisions.



Target population and subgroups


Describe characteristics of the base case population and subgroups analysed, including why they were chosen.


Setting and location


State relevant aspects of the system(s) in which the decision(s) need(s) to be made.


Study perspective


Describe the perspective of the study and relate this to the costs being evaluated.




Describe the interventions or strategies being compared and state why they were chosen


Time horizon


State the time horizon(s) over which costs and consequences are being evaluated and say why appropriate.


Discount rate


Report the choice of discount rate(s) used for costs and outcomes and say why appropriate.


Choice of health outcomes


Describe what outcomes were used as the measure(s) of benefit in the evaluation and their relevance for the type of analysis performed.


Measurement of effectiveness


Single study-based estimates: Describe fully the design features of the single effectiveness study and why the single study was a sufficient source of clinical effectiveness data.



Synthesis-based estimates: Describe fully the methods used for identification of included studies and synthesis of clinical effectiveness data


Measurement and valuation of preference based outcomes


If applicable, describe the population and methods used to elicit preferences for outcomes.


Estimating resources and costs


Single study-based economic evaluation: Describe approaches used to estimate resource use associated with the alternative interventions. Describe primary or secondary research methods for valuing each resource item in terms of its unit cost. Describe any adjustments made to approximate to opportunity costs.



Model-based economic evaluation: Describe approaches and data sources used to estimate resource use associated with model health states. Describe primary or secondary research methods for valuing each resource item in terms of its unit cost. Describe any adjustments made to approximate to opportunity costs.


Currency, price date, and conversion


Report the dates of the estimated resource quantities and unit costs. Describe methods for adjusting estimated unit costs to the year of reported costs if necessary. Describe methods for converting costs into a common currency base and the exchange rate.


Choice of model


Describe and give reasons for the specific type of decision analytical model used. Providing a figure to show model structure is strongly recommended.




Describe all structural or other assumptions underpinning the decision-analytical model.


Analytical methods


Describe all analytical methods supporting the evaluation. This could include methods for dealing with skewed, missing, or censored data; extrapolation methods; methods for pooling data; approaches to validate or make adjustments (such as half cycle corrections) to a model; and methods for handling population heterogeneity and uncertainty.



Study parameters


Report the values, ranges, references, and, if used, probability distributions for all parameters. Report reasons or sources for distributions used to represent uncertainty where appropriate. Providing a table to show the input values is strongly recommended.


Incremental costs and outcomes


For each intervention, report mean values for the main categories of estimated costs and outcomes of interest, as well as mean differences between the comparator groups. If applicable, report incremental cost effectiveness ratios.


Characterising uncertainty


Single study-based economic evaluation: Describe the effects of sampling uncertainty for the estimated incremental cost and incremental effectiveness parameters, together with the impact of methodological assumptions (such as discount rate, study perspective).



Model-based economic evaluation: Describe the effects on the results of uncertainty for all input parameters, and uncertainty related to the structure of the model and assumptions.


Characterising heterogeneity


If applicable, report differences in costs, outcomes, or cost effectiveness that can be explained by variations between subgroups of patients with different baseline characteristics or other observed variability in effects that are not reducible by more information.



Study findings, limitations, generalisability, and current knowledge


Summarise key study findings and describe how they support the conclusions reached. Discuss limitations and the generalisability of the findings and how the findings fit with current knowledge.



Source of funding


Describe how the study was funded and the role of the funder in the identification, design, conduct, and reporting of the analysis. Describe other non-monetary sources of support.


Conflicts of interest


Describe any potential for conflict of interest of study contributors in accordance with journal policy. In the absence of a journal policy, we recommend authors comply with International Committee of Medical Journal Editors recommendations

Table 4

Philips criterion [25, 26]

Dimensions of quality

Questions for critical appraisal

Response (Yes/no/partial/unclear/NA)


S1: Statement of decision problem/objective

Is there a clear statement of the decision problem?


Is the objective of the evaluation and model specified and consistent with the stated decision problem?


Is the primary decision maker specified?


S2: Statement of scope/perspective

Is the perspective of the model stated clearly?


Are the model inputs consistent with the stated perspective?


Has the scope of the model been stated and justified?


Are the outcomes of the model consistent with the perspective, scope and overall objective of the model?


S3: Rationale for structure

Has the evidence regarding the model structure been described?


Is the structure of the model consistent with a coherent theory of the health condition under evaluation?


Have any competing theories regarding model structure been considered?


Are the sources of data used to develop the structure of the model specified?


Are the causal relationships described by the model structure justified appropriately?


S4: Structural assumptions

Are the structural assumptions transparent and justified?


Are the structural assumptions reasonable given the overall objective, perspective and scope of the model?


S5: Strategies/comparators

Is there a clear definition of the options under evaluation?


Have all feasible and practical options been evaluated?


Is there justification for the exclusion of feasible options?


S6: Model type

Is the chosen model type appropriate given the decision problem and specified causal relationships within the model?


S7: Time horizon

Is the time horizon of the model sufficient to reflect all important differences between options?


Is the time horizon of the model, and the duration of treatment and treatment effect described and justified?


Has a lifetime horizon been used? If not, has a shorter time horizon been justified?


S8: Disease states/pathways

Do the disease states (state transition model) or the pathways (decision tree model) reflect the underlying biological process of the disease in question and the impact of interventions?


S9: Cycle length

Is the cycle length defined and justified in terms of the natural history of disease?


D1: Data identification

Are the data identification methods transparent and appropriate given the objectives of the model?


Where choices have been made between data sources, are these justified appropriately?


Has particular attention been paid to identifying data for the important parameters in the model?


Has the process of selecting key parameters been justified and systematic methods used to identify the most appropriate data?


Has the quality of the data been assessed appropriately?


Where expert opinion has been used, are the methods described and justified?


D2: Pre-model data

Are the pre-model data analysis methodology based on justifiable statistical and epidemiological techniques?


D2a: Baseline data

Is the choice of baseline data described and justified?


Are transition probabilities calculated appropriately?


Has a half cycle correction been applied to both cost and outcome?


D2b: Treatment effects

If relative treatment effects have been derived from trial data, have they been synthesised using appropriate techniques?


Have the methods and assumptions used to extrapolate short-term results to final outcomes been documented and justified? Have alternative assumptions been explored through sensitivity analysis?


Have assumptions regarding the continuing effect of treatment once treatment is complete been documented and justified? Have alternative assumptions been explored through sensitivity analysis?


D2c: Quality-of-life weights (utilities)

Are the utilities incorporated into the model appropriate?


Is the source for the utility weights referenced?


Are the methods of derivation for the utility weights justified?


D3: Data incorporation

Have all data incorporated into the model been described and referenced in sufficient detail?


Has the use of mutually inconsistent data been justified (i.e. are assumptions and choices appropriate)?


Is the process of data incorporation transparent?


If data have been incorporated as distributions, has the choice of distribution for each parameter been described and justified?


D4: Assessment of uncertainty

Have the four principal types of uncertainty been addressed?


If not, has the omission of particular forms of uncertainty been justified?


D4a: Methodological

Have methodological uncertainties been addressed by running alternative versions of the model with different methodological assumptions?


D4b: Structural

Is there evidence that structural uncertainties have been addressed via sensitivity analysis?


D4c: Heterogeneity

Has heterogeneity been dealt with by running the model separately for different sub-groups?


D4d: Parameter

Are the methods of assessment of parameter uncertainty appropriate?


Has probabilistic sensitivity analysis been done, if not has this been justified?


If data are incorporated as point estimates, are the ranges used for sensitivity analysis stated and justified?


C1: Internal consistency

Is there evidence that the mathematical logic of the model has been tested thoroughly before use?


C2: External consistency

Are the conclusions valid given the data presented?


Are any counterintuitive results from the model explained and justified?


If the model has been calibrated against independent data, have any differences been explained and justified?


Have the results of the model been compared with those of previous models and any differences in results explained?


To initially assess the quality of included studies, a score of 1 will be given to items within the CHEERS checklist that can be answered ‘yes’, 0.5 for items only partially addressed, 0 for ‘no’ and where an item is identified as not applicable, no score will be given. The score will then be totalled and calculated as a percentage of the total score that could be achieved for that study, thus taking into account elements of the checklist which were deemed not applicable. This is an approach that has previously been used [27], and although it is acknowledged that by assigning equal weighting to each criteria may not truly reflect the importance of each of the checklist items, it is thought that it will provide a broad overview of the quality of studies included, which will then pave way for more detailed analysis on individual checklist items. These evaluations will be included in any publication as supplementary material where feasible.

Methodological variation between studies is likely to prevent a pooling of economic data in the form of a meta-analysis, and therefore, results of the studies will be presented and discussed in a qualitative manner according to the study type.


This systematic review will provide a comprehensive assessment of the type and quality of economic research used in the evaluation of interventions to prevent and treat eczema. The results of the review are likely to be written up in multiple publications, one focusing on an overview of the state of the art with additional papers focusing in more detail on particular methodologically aspects (for instance, the methods used in modelling studies). The review will report the range of cost-effectiveness estimates found for interventions to prevent and treat atopic eczema, which may be useful in informing clinicians and decision makers about the relative value of different interventions for eczema and enable the value of eczema interventions to be compared with the cost effectiveness for other interventions in other disease areas. That is, it may help decision makers, on the basis of current information (if sufficient), to be able to answer questions about how to allocate limited resources between eczema and other disease areas and once allocated to eczema how to use those limited resources efficiently to maximise outcomes from eczema care. The review will also be of interest to methodologists interested in the range and quality of economic studies in this clinical field. Finally, this systematic review will help identify gaps in the current evidence base surrounding the economics of eczema to inform further research efforts in this area.



Consolidated Health Economic Evaluation Reporting Standards


General Practitioner


Global Resource for Eczema Trials


Health-Related Quality of Life


Incremental Cost Effectiveness Ratio


James Lind Alliance


Not Applicable


National Health Service


National Institute of Health and Care Excellence


Priority Setting Partnership


Quality Adjusted Life Years


United Kingdom



This systematic review is independent research arising from Tracey Sach’s Career Development Fellowship (CDF-2014-07-006) supported by the National Institute for Health Research. The views expressed in this publication are those of the author(s) and not necessarily those of the NHS, the National Institute for Health Research or the Department of Health.

The following individuals are acknowledged as providing advice as research mentors (Professor Kim Thomas, Dr Nicky Welton, Professor Andrew Briggs) and as part of the annual advisory panel (Dr Tom Kenny, Dr Nick Levell, Fiona McOwan, Jo Parris, Amanda Roberts, Professor Lee Shepstone, Professor Fujian Song and Dr Edward Wilson).

Authors’ contributions

TS conceptualised the research plan for the proposed systematic review and wrote the manuscript. EM and CM contributed to the writing of the manuscript. NL provided expertise on eczema. All authors reviewed the manuscript for important intellectual content and approved the final manuscript. TS is the guarantor.

Competing interests

The authors declare that they have no competing interests.

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (, which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated.

Authors’ Affiliations

Health Economics Group, Norwich Medical School, University of East Anglia, Norwich, NR4 7TJ, UK
Dermatology Department, Norfolk and Norwich University Hospitals NHS Foundation Trust, Colney Lane, Norwich, NR4 7UY, UK


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© Sach et al. 2016


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