Prioritisation of dermatological research

General points about prioritisation

Other points, apart from burden of disease, to consider in priority setting:
  • Equity (influence on vulnerable populations)
  • Cost-effectiveness
  • Intervention availability
  • Interest group advocacy (charity revenue)
  • Capacity building
  • Infrastructure availability
  • Disease transmissibility
  • Problem magnitude
  • Impact of an intervention on policy or treatment change
  • Public interest
  • Emerging evidence that may necessitate production of new reviews, public interest
  • Opportunity for scientific innovation
  • Existence of other systematic reviews
  • Availability of public funding
  • Health importance
  • Knowledge gap
  • Adopting principles set forth by other organizations
  • Patient focus
  • Availability of primary studies for review, the number and type of treatment options for a given condition or population, disease trends

Cochrane's priority framework

  • Engage with external partners such as World Health Organisation (WHO) and Pan American Health Organization (PAHO) to improve our ability to reflect priorities that represent global needs and ensure that by the end of 2016, 20% of the titles on the list are relevant to low and middle-income countries (LMICs).
  • Encourage all groups to engage in a formal prioritisation process based on consultation with one or more external stakeholders groups such as funders, health professionals, consumers, guidelines agencies or healthcare policy makers.
  • Ensure a focus on global health priorities. In 2016 Cochrane will work to strengthen our formal and informal partnerships with organisations such as the WHO and the Pan American Health Organization (PAHO), and to explore new partnerships with groups such as Euroscan in the context of priority setting. Members of the CET will aim to work with WHO to ensure that Cochrane is producing reviews that contribute to evidence-informed decision-making within the framework of Universal Health Coverage (UHC). Cochrane will also capitalise on the newly formed relationship between Cochrane and PAHO. A key aim of the Memorandum of Understanding signed by the two organisations is to align Cochrane systematic review production to PAHO’s health priorities.

Cochrane aim to increase the percentage of LMIC relevant reviews from the current figure of 12% to a minimum of 20% by the end of 2016. Cochrane does not anticipate that every CRG will contribute to this target equally; however, it is felt that we can utilise the knowledge and skills of colleagues inside and outside Cochrane to identify gaps and use this information to help CRGs who might not have prioritised LMICs previously.

Examples of justification of importance of titles:

  • Commissioned by a major regional or international guideline group
  • Commissioned by a major regional or international funder
  • Potential for health or health system impact, or a high cost intervention, including potential for disinvestment
  • Access or citation data for existing reviews, to justify an update
  • Identified following a formal consultation process e.g. James Lind Alliance
  • Recognised emerging priority for specific stakeholders e.g. global health emergency
  • Flagged by a regional or international early awareness and alert (EAA) system e.g. Euroscan

References & key points from each paper

1. The global burden of skin disease in 2010: an analysis of the prevalence and impact of skin conditions. Hay RJ, Johns NE, Williams HC, Bolliger IW, Dellavalle RP, Margolis DJ, Marks R, Naldi L, Weinstock MA, Wulf SK, Michaud C, J L Murray C, Naghavi M. J Invest Dermatol. 2014 Jun;134(6):1527-34. doi: 10.1038/jid.2013.446. Epub 2013 Oct 28. PubMed PMID: 24166134. (Download here)

2. The global challenge for skin health. Hay RJ, Augustin M, Griffiths CE, Sterry W; Board of the International League of Dermatological Societies and the Grand Challenges Consultation groups. Br J Dermatol. 2015 Jun;172(6):1469-72. doi: 10.1111/bjd.13854. PubMed PMID: 26036149. (Download here)

3. Global burden of skin disease as reflected in Cochrane Database of Systematic Reviews. Karimkhani C, Boyers LN, Prescott L, Welch V, Delamere FM, Nasser M, Zaveri A, Hay RJ, Vos T, Murray CJ, Margolis DJ, Hilton J, MacLehose H, Williams HC, Dellavalle RP. JAMA Dermatol. 2014 Sep;150(9):945-51. doi: 10.1001/jamadermatol.2014.709. PubMed PMID: 24807687. (Download here)

4. Alignment of systematic reviews published in the Cochrane Database of Systematic Reviews and the Database of Abstracts and Reviews of Effectiveness with global burden-of-disease data: a bibliographic analysis. Yoong SL, Hall A, Williams CM, Skelton E, Oldmeadow C, Wiggers J, Karimkhani C, Boyers LN, Dellavalle RP, Hilton J, Wolfenden L. J Epidemiol Community Health. 2015 Jul;69(7):708-14. doi: 10.1136/jech-2014-205389. Epub 2015 Apr 17. Review. PubMed PMID: 25888595; PubMed Central PMCID: PMC4483792. (Download here)

5. Comparing cutaneous research funded by the US National Institutes of Health (NIH) with the US skin disease burden. Hagstrom EL, Patel S, Karimkhani C, Boyers LN, Williams HC, Hay RJ, Weinstock MA, Armstrong AW, Dunnick CA, Margolis DJ, Dellavalle RP. J Am Acad Dermatol. 2015 Sep;73(3):383-91.e1. doi: 10.1016/j.jaad.2015.04.039. Epub 2015 Jun 4. PubMed PMID: 26051697. (Download here)

6. Comparative effectiveness of topical drugs in dermatologic priority diseases: geometry of randomized trial networks. Maruani A, Samimi M, Lorette G, le Cleach L. J Invest Dermatol. 2015 Jan;135(1):76-83. doi: 10.1038/jid.2014.296. Epub 2014 Jun 21. PubMed PMID: 25046338. (Download here)

7. Identifying gaps in research prioritization: The global burden of neglected tropical diseases as reflected in the Cochrane database of systematic reviews. Bhaumik S, Karimkhani C, Czaja CA, et al. Journal of Family Medicine and Primary Care. 2015;4(4):507-513. doi:10.4103/2249-4863.174266. (Download here)

1.      The Global Burden of Skin Disease in 2010: an analysis of the prevalence and impact of skin conditions (2014)

  • "Three skin conditions were in the top 10 most prevalent diseases globally in 2010—fungal skin diseases, other skin and subcutaneous diseases, and acne vulgaris. There are further five skin diseases in the top 50 most common causes of disease—pruritus, eczema, impetigo, molluscum contagiosum/warts, and scabies.
  • The leading cause of skin condition disability-adjusted life years (DALYs) is eczema, when looking across countries, ages, sex, and time because of the combined high prevalence across geographies and population and relatively high average disability weight.
  • In delivering data on skin disease, the team encountered a number of methodological problems. The classification of skin disease was derived from International Classification of Disease 10, which led to the inclusion of most diseases seen in dermatology clinics under skin, but other skin problems under other medical specialities. The best examples of this are melanoma, which presents in skin clinics but is reported under cancer, and certain infections such as cutaneous leishmaniasis, which is reported under infectious disease."

 2.      The global challenge for skin health (2015)

  • “The effects of genetic diseases, such as the widespread blistering due to epidermolysis bullosa and the loss of sun-protecting melanin pigmentation in albinism, are huge, and yet some of the greatest scientific advances have been made in these fields with the delineation of the causal single-gene mutations. Albinism, as with other skin conditions, leads to great stigma in many lands and is a determinant of early onset and rapidly fatal skin cancers, as well as visual loss, social isolation, persecution and, in some countries, ritual murder. Combating these social consequences is now listed as a high priority in sub-Saharan Africa by the United Nations Commission on Human Rights, but this needs to be linked explicitly to the effects of albinism on health.
  • In adults, chronic inflammatory skin disease, such as psoriasis, stands out as the most frequent cause of persistent and disfiguring skin change, but in many this is compounded by severe arthritis. There is a growing appreciation that psoriasis is a complex, systemic disease associated with significant morbidity and mortality due to cardiovascular disease and depression.
  • Occupational skin disease such as hand eczema is a major cause of work-related disability.
  • Melanoma affects adults in all walks of life and has become the second most frequent cancer in some areas of the world; its incidence increases from early adult life, despite international initiatives to encourage prevention and screening.
  • The elderly are not immune to skin diseases. Arterial and venous ulceration, complicated by poor wound healing and pruritus or severe itching, rob them of the fruits of a global aspiration to healthy ageing. Nonmelanoma skin cancers are a further threat in old age, with a steadily increasing rise in prevalence in the over 70s despite increased awareness and surveillance, and the proliferation of preventive measures.
  •  Beyond the individual burden, nonmelanoma skin cancer is an economic threat to many health systems. In Australia, for instance, it is the most costly form of cancer.
  • With psoriasis and eczema, an expanding knowledge of the immunology and genetic basis of these conditions has led to the discovery of new families of medicines and biological agents that target immune pathways important in disease development, leading to effective and safe therapies.
  • New diagnostic and imaging tools provide powerful weapons to combat skin cancers, from dermatoscopic devices to molecular markers of infection, and from surgical advances including micrographic excision techniques to biological antagonists against the signalling pathways involved in carcinogenesis, all coupled with well-designed public education and preventive programmes. In the poorest countries the adoption of simple measures such as integrated care pathways for patients with limb ulceration or lymphoedema due to different causes has the potential to make a huge impact on the lives of patients and their communities.
  • In Europe the annual cost of occupational dermatitis – including the direct costs of treatment and industrial compensation, as well as the indirect costs of sick leave and loss of productivity is estimated to be greater than €5 billion.
  • In moderate-to-severe psoriasis the annual cost of the disease in the U.S.A., including treatment and loss of productivity, was estimated to be $11.25 billion.
  • Education of frontline health workers in the elements of skin disease is also key to successful management. A new drive to integrate the core skills and knowledge needed to ensure freedom from skin problems into undergraduate and postgraduate teaching for health professionals could provide the answer.
  • The recent actions by the World Health Organization in framing a resolution to member states for concerted action on psoriasis and in recognizing scabies as a neglected disease provide a huge impetus for change.”

3.      Global burden of skin disease as reflected in Cochrane Database of Systematic Reviews (CDSR) (2014)

  • “Comparing the number of reviews/protocols and disability, dermatitis, melanoma, nonmelanoma skin cancer, viral skin diseases, and fungal skin diseases were well matched in terms of representation in the CDSR. Decubitus ulcer, psoriasis, and leprosy demonstrated review/protocol overrepresentation when matched with corresponding DALYs. In comparison, acne vulgaris, bacterial skin diseases, urticaria, pruritus, scabies, cellulitis, and alopecia areata were underrepresented in CDSR when matched with corresponding DALYs.
  • While burden of disease data inform prioritization, other criteria include influence on vulnerable populations (equity), cost, availability and lack of costeffective interventions, interest-group advocacy (charity revenue), disease transmissibility, public interest, opportunity for scientific innovation, and infrastructure building.
  • Conditions for which CDSR representation was appropriate for associated disability: dermatitis had both the greatest CDSR representation and the highest DALY ranking. The CDSR representation of melanoma and nonmelanoma skin cancer (7 and 6 systematic reviews and protocols, respectively) correlates with their relatively low percentage of total 2010 DALYs and DALY rankings. Similarly, disability and review and protocol representation appear well-matched for viral skin diseases and fungal skin diseases.
  • Conditions for which CDSR representation were too high for associated disability: decubitus ulcer was represented by 10 systematic reviews and 5 protocols but had the fifth lowest percentage of total 2010 DALYs of the 15 skin conditions. Similarly, psoriasis had the third highest review and protocol representation (n = 11) but the third lowest percentage of total 2010 DALYs. Leprosy was also overrepresented in CDSR by 4 systematic reviews, while this condition demonstrated a significant 82% decrease in global DALYs from 1990 to 2010, ranking 175th in 2010 of all 176 conditions ranked by global burdon of disease (GBD) 2010.
  • Conditions for which CDSR representation was too low for associated disability: at the lower end of the representation spectrum, acne vulgaris and bacterial skin diseases had 10 and 5 reviews and protocols, respectively, but the second and third highest percentage of total 2010 DALYs. The GBD 2010 disability data for these 2 conditions demonstrate similar global disability “hot spots” in Africa, particularly Nigeria for acne vulgaris and Mozambique for bacterial skin diseases. The most common dermatologic disorder seen in emergency departments, urticaria, was underrepresented in CDSR when matched with its fifth highest percentage of total 2010 DALYs of the 15 skin conditions. Pruritus was similarly underrepresented. Perhaps these may be topics for future expansion in CDSR. However, DALY rates for both conditions remained constant from 1990 to 2010, which may partially explain their low CDSR representation.
  • It may be entirely appropriate to have overrepresentation of a topic if, for example, the disease disproportionately affects disadvantaged populations and health equity becomes a high priority in research allocation. This was noted herein to be the case for leprosy, but it is also particularly relevant for neglected tropical diseases for which the World Health Organization has called for allocation of additional research funds to “promote equity in the distribution of resources.” As an example, factors considered by the Cochrane Skin Group to accept and prioritize topics for future Cochrane reviews include their impact on people’s lives (surrogate for burden of disease), knowledge gap, existence of other systematic reviews, availability of public funding, and whether the topics are of great current interest or public health importance.”

4.      Alignment of systematic reviews published in the Cochrane Database of Systematic Reviews and the Database of Abstracts and Reviews of Effectiveness with global burden-of-disease data: a bibliographic analysis (2015)

  • “There was a significant correlation between percentage DALYs and systematic reviews published in CDSR and DARE databases. There was no significant correlation between percentage mortality and number of systematic reviews published in either database.
  • Mortality and morbidity (assessed using DALYs) are frequently used indices of burden of disease.
  • Although useful, the burden-of-disease estimates including percentage of mortality and DALYs represent just one source of data available to prioritise systematic review activity. Other factors, including the availability of primary studies for review, the number and type of treatment options for a given condition or population, disease trends, emerging evidence that may necessitate production of new reviews, public interest and the presence of disease types which have been established for a longer period of time are among other important considerations that may impact on systematic review output, and are not currently addressed in this manuscript.”

5.      Comparing cutaneous research funded by the US National Institutes of Health (NIH) with the US skin disease burden (2015)

  • “Comparing disability-adjusted life year (DALY) disability estimates with disease funding, melanoma, NMSC, and leprosy were overfunded. Dermatitis, acne vulgaris, pruritus, urticaria, decubitus ulcer, fungal skin diseases, alopecia area, cellulitis, and scabies were underfunded. Burden and funding appeared well matched for bacterial skin diseases, viral skin diseases, and psoriasis.”
  • There are important limitations of using Global Burden of Disease (GBD) to inform or influence NIH spending: differences in US-specific disease burden, availability of treatment options (conditions with validated and established therapies, even with high disease burden, may warrant less NIH funding dollars than conditions with moderate disease burden but lacking treatment options), lower burden disease areas that are on the verge of a breakthrough or that may effect change and overcome health inequalities, [anticipation of] priorities that will emerge in future years.
  • “Future directions for the NIH may include adopting principles set forth by other organizations. The Patient-Centered Outcomes Research Institute operates under 3 goals:
    • increase the quantity, quality, and timeliness of comparative research;
    • accelerate implementation of research evidence; and
    • promote patient-centered research projects. Results that are patient-centered and likely to change clinical practice are given high priority; NIH goals lack both of these criteria.
  • The Health Technology Assessment program in the United Kingdom also provides an exemplary priority-setting process. Health Technology Assessment uses evidence via published systematic reviews linked to cost-effectiveness on a particular topic. In addition, recommendations from physicians and policy makers for commissioned research are thoroughly analyzed. Health Technology Assessment operates on a fine balance between commissioner- and researcher-led projects, all the while accounting for cost-effectiveness and public health relevance.”

6.      Comparative Effectiveness of Topical Drugs in Dermatologic Priority Diseases: Geometry of Randomized Trial Networks (2014)

  • The Institute of Medicine for the Comparative Effectiveness Research (CER) initiative based in the US, which launched in 2009, established 100 initial priority topics. Topics were ranked by quartiles. Among them, three directly concerned the assessment of topical treatments in dermatologic conditions: psoriasis, chronic lower-extremity wounds (CLEWs), and acne vulgaris (AV).
  • The authors aimed to perform a network analysis of RCTs on topical drugs for psoriasis, CLEWs, and AV published during a recent 5-year period. In particular, they sought to determine the number of topical drugs used for each of these conditions, whether some are disproportionately preferred or neglected in clinical trials, and the proportion of trials using inactive comparators so as to detect gaps in the existing evidence that should dictate the future research agenda. The results do not suggest a substantial lack of head-to-head evidence for mild psoriasis and AV, but for CLEWs results are more questionable. Although the authors demonstrated no significant avoidance of comparisons in trials on CLEWs, inactive controls were highly represented. Also, as clinicians, the authors noted only a few comparisons of drugs with a close mode of action, such as antiseptics and nonsteroidanti-inflammatory drugs, antibiotics and silver, or protease inhibitors and growth factors.

 (Text taken from the paper)

7.      Identifying gaps in research prioritization: The global burden of neglected tropical diseases (NTDs) as reflected in the Cochrane database of systematic reviews (2015)

  • “Results indicate the need for increased prioritization of systematic reviews on neglected tropical diseases (NTDs), particularly diagnostic test accuracy reviews.
  • The following 18 NTDs were studied by GBD: Chagas disease, leishmaniasis, human African trypanosomiasis, schistosomiasis, cysticercosis, echinococcus, lymphatic filariasis, onchocerciasis, trachoma, dengue, yellow fever, rabies, ascariasis, trichuriasis, hookworm disease, foodborne trematodiases, leprosy, and other NTDs.
  • Prioritization of DTA reviews is a potential area for CDSR expansion since diagnostic tests are pivotal components of healthcare decisions for early intervention. In order to accomplish disease eradication, WHO has underlined the need for targeted research to develop accessible new diagnostics for NTDs.
  •  Greater than 40% of NTD reviews in CDSR lacked an author from endemic regions, highlighting a need to build synthesized research capacity in low- and middle-income nations.”