ACCISS MULTI-STAKEHOLDER MEETING TOOL CATALOGUE

A TOOLBOX FOR IMPROVING ACCESS TO INSULIN IN LOW-AND MIDDLE-INCOME COUNTRIES

Diabetes has been described as one of the largest global health emergencies of the 21st century with an estimated 415 million people currently affected worldwide (1). This number is
expected to rise to 642 million by 2040. Reports suggest that 77 percent of individuals living with diabetes live in low- and middle-income countries (LMICs) and 90 percent of new cases
of diabetes will occur in these countries.

Africa has the highest percentage of undiagnosed people (~67 percent) and one in ten people in the Middle East and North Africa have diabetes (1). Moreover, in developing countries
those affected most frequently are between the ages of 35 and 64, their most economically productive years (2). Further, more than half a million children under the age of 14 are living
with type 1 diabetes (1). Reports suggest that children in sub-Saharan Africa newly diagnosed with type 1 diabetes often have a life expectancy of less than one year (3).

Despite these striking statistics, little has been done to address access to insulin, which is essential for the survival of people with type 1 diabetes
and is often required for optimal management of type 2 diabetes to avoid devastating consequences (4).

Considering this, an innovative global study, Addressing the Challenge and Constraints of Insulin Sources and Supply (ACCISS), was launched to
study the barriers to access of insulin on a global level. It is managed by Health Action International in collaboration with the University of Geneva
and Boston University School of Public Health. The ACCISS study aims to further characterise the inequities and inefficiencies in the global insulin
market with the goal of developing a scientific approach to address these challenges (5).

ACCISS Tools

In keeping with the ACCISS goals, this collection of tools aim to present national and international health policymakers and others with a better
understanding of the underlying parameters that define universal access (and the lack thereof) to insulin for people living with type 1 and 2 diabetes
in LMICs. They describe current evidence on practical choices and questions related to access to insulin in LMICs, and provide recommendations for
stakeholders interested in improving access to insulin.

Included in this catalogue are summaries of the tools which will be discussed during the ACCISS Multi-stakeholder Meeting on 11 September. They
make up some of the tools that will eventually be housed in the ACCISS online toolbox.

References
1. International Diabetes Federation Diabetes Atlas 7th Edition: International Diabetes Federation; 2015.
2. Diabetes Action Now: World Health Organization and International Diabetes Federation; 2004.
3. The Africa Diabetes Care Initiative 2010-2012: International Diabetes Federation.
4. Beran D, Ewen M, Laing R. Constraints and challenges in access to insulin: a global perspective. The lancet Diabetes & endocrinology 2016;4:275-85.
5. Beran D EM, Laing R. Access to insulin: Current Challenges and Constraints. Amsterdam: Health Action International; 2015.

Toolbox Poster Session...................P.2

Review of the Evidence on Insulin and Its Use in Diabetes.........................P.2
Interchangeability of Biosimilars in the European Union............................P.3
Alternative Funding Mechanisms for Insulin.........................................P.3
Guidelines for Insulin Donations in Low- and Middle-Income Countries..........P.4
Regulating Mark-ups and other Add-ons in the Supply Chain.......................P.4
The Road to Free Insulin: Country Case Studies.................................P.5/P.6
Costing Model for Universal Diabetes Care..........................................P.7
The Fair Price of Analogue Insulin when Compared Against Human Insulin.....P.7

TOOLBOX POSTER SESSION

Multiple authors

The following posters will be presented during the meeting. Many of these correspond to papers included in this catalogue (please see page
references here)
• Guidelines for Insulin Donations in LMICs (see page 4)
• The Fair Price of Analogue Insulin when Compared Against Human Insulin: (see page 7)
• What is Needed to Manage Diabetes in LMICs? The Eleven
Essential Elements
• Regulating Mark-ups and other Add-ons in the Supply Chain (see page 4)
• Paying the Price: Insulin Prices, Availability and Affordability in 13 LMICs
• Review of the Evidence on Insulin and Its Use in Diabetes (see page 2)
• Costing Model for Universal Diabetes Care (see page 7)

REVIEW OF THE EVIDENCE ON INSULIN AND ITS USE IN DIABETES

Sylvia Kehlenbrink, MD et alEndocrinology Fellow I Brigham and Women’s Hospital
Senior Fellow I Harvard Humanitarian Initiative

Short description of the tool

This document reviews in detail all relevant evidence on four important clinical topics:
1. Clinical outcomes of human versus analogue insulin
2. Clinical outcomes of pen delivery versus syringe and vial
3. Use of insulin in type 2 diabetes
4. Interchangeability of common insulins and biosimilars
NB: See also tools on the comparative cost-effectiveness of insulins and the interchangeability of biosimilars

Who is this tool for?

The document is directed towards national and institutional formulary committees, committees preparing national clinical guidelines on the use of
insulin, and reimbursement authorities, with a focus on low-resource settings.

How is it used?
This information can be used when formulating evidence-based recommendations on national clinical guidelines and reimbursement decisions.

Key points from the tool

• For people living with diabetes requiring insulin in low resource settings, human insulin should remain first line therapy. Analogue insulin,
particularly basal insulin, should be available for a small subset of people with severe insulin deficiency for whom all risk factors for hypoglycaemia
have been addressed but continue to exhibit recurrent severe hypoglycaemia.
• Although pen devices appear to be preferable in terms of treatment adherence and persistence, as well as quality of life, the data to support
improved clinical outcomes is lacking. Therefore, in settings where resources are limited, the use of the more affordable vial and syringe is
encouraged and justified.
• The decision to use insulin in type 2 diabetes depends on the degree of insulin deficiency of the individual and the effectiveness (or lack thereof) of
non-insulin agents. The decision to add insulin depends on the individual glycaemic target, hypoglycaemia risk, and individual/system-level
affordability. A conceptual framework to guide the use of insulin in type 2 diabetes using medications included in the 2017 WHO Model List of
Essential Medicines is presented.
• Current guidelines state that biosimilarity and interchangeability are not the same. Therefore, caution is needed when switching from one insulin to
another. Glucose monitoring, follow-up, and comprehensive diabetes education for patients and clinicians remain needed.

INTERCHANGEABILITY OF BIOSIMILARS IN THE EUROPEAN UNION

Dr. Thijs Giezen
Foundation Pharmacy for Hospitals in Haarlem
Member of the Medicines Evaluation Board, Netherlands

Short description of the tool

This document contains information on the different regulatory approaches of the FDA and the EMA towards the interchangeability of biosimilars, and
presents updated information on studies in which patients switched from an insulin reference product to a biosimilar, and advice on the use of
biosimilars in clinical practice.

Who is this tool for?

This document is directed towards national regulators, national and institutional formulary committees, committees preparing national clinical
guidelines on the use of insulin and biosimilars, and reimbursement authorities.

How is it used?
The information from this document may promote understanding of the different regulatory pathways between the FDA and the EMA, and in reaching
clinical and reimbursement decisions on the use of biosimilar insulins in the national situation.

Key points from the tool

• The FDA and the EMA have different regulatory approaches towards biosimilars.
• The EMA has a rigorous approval process for biosimilars showing convincing data on similar quality, safety and efficacy; regulatory approval
basically implies interchangeability, and that switching can safely be done.
• The FDA considers insulin biosimilars as small molecules. Market approval does not automatically imply interchangeability in clinical practice, for
which separate switching studies are needed.
• Switching studies are rare. Up till mid-2017, two biosmilars to insulin glargine have been approved by the EMA, and one (by Biocon) by the
Japanese authorities. The FDA has issued one provisional approval (see also ‘Guidelines on the Selection of Insulin’).
• Based on the rigorous regulatory pathway, ten years of clinical practice in the EU and emerging clinical evidence, there is increased confidence
that switching is safe.
ALTERNATIVE FUNDING SOURCES TO IMPROVE INSULIN ACCESS
Jing Luo, MD
Instructor in Medicine, Program on Regulation, Therapeutics, and Law (PORTAL)
Harvard Medical School, Brigham and Women’s Hospital

Short description of the tool

This document presents a literature review of four alternative
financing strategies to increase funding universal health care
coverage and insulin in LMICs, with a discussion on the pros and cons of each method. The four possible strategies discussed are:
1) A tax on sugar-sweetened beverages earmarked for insulin
2) An international transaction tax to support insulin procurement
3) A Trademark based revenue generation approaches
4) Social impact bonds

Who is this tool for?

The target audience of this report are national and international policymakers, health or finance officials, and advocates who are interested in
improving access to insulin and diabetes-related care in LMICs. Strategies 1 and 4 are national strategies; strategies 2 and 4 require international
collaboration.

How is it used?
This document can be used as background information when considering alternative funding mechanisms, with several references to practical
examples and more detailed information.

Key points from the tool

• These four approaches have varying degrees of empirical success. An excise tax on soft drinks currently has the best potential for national
replication.
• An excise tax on soft drinks can reduce consumption of taxed beverages and increase revenues at the same time (e.g. in Mexico). The effect is
more marked with low-income households; this effect can be compensated by earmarking the earnings for programmes for the poor, e.g. child
obesity or diabetes type 1 in children.
• International transaction taxes on commercial flights (e.g. UNITAID) have generated large amounts of new revenue for lower-cost antiretrovirals,
anti-malarials and anti-TB treatments. However, the programmes have not been expanded to non-communicable diseases such as diabetes.
• Trademark-based revenue generation, e.g. (Red), has raised hundreds of millions of dollars for the Global Fund, but similarly does not address
diabetes related care.
• An early model for a social impact bond (i.e. financial contract between government an intermediary organisation and private investors) to improve
insulin access is theoretically presented but not yet ready for large-scale implementation.

REGULATING MARK-UPS AND OTHER ADD-ONS IN THE SUPPLY CHAIN

Douglas Ball
Pharmaceutical Consultant, India

Short description of the tool

This document contains an overview of the various price components (mark-ups, taxes etc) in the supply chain that all contribute to the final price to
the consumer, with many country examples and references. The document also identifies a list of possible interventions to reduce the barriers to
access that these mark-ups may create, especially for those in resource poor settings and disadvantaged that have no access to free or subsidised
insulin in the public sector.

Who is this tool for?

The tool is directed towards national policy makers, national price regulation authorities, high-level policy makers in health, financing and economics,
and national diabetes programmes.

How is it used?
The document identifies the various mark-ups, taxes, tariffs, and other add-ons that add to the final price of insulin, and presents a check-list of
potential interventions at country level to reduce their impact on insulin prices.

Key points from the tool

• The price of insulin has a substantial impact on access among the poor. Lack of public sector availability forces those who need it to buy out-of-
pocket from private retailers
• Cumulative mark-ups on medicines in LMICs vary between 11 percent and 6,894 percent, but data on insulin are limited.
• Six recent case studies on insulin price components in LMICs showed no clear trends. Differences in mark-up levels were country-specific.
• Many LMICs have weak price regulation whilst most OECD countries regulate price components, such as wholesaler and retailer mark-ups, as part
of a comprehensive pricing strategy.
• Apart from good public procurement practice and the removal of tariffs and taxes, there is no one-size-fits-all approach. Price regulation requires
careful assessment of the local insulin market, cost drivers and incentives.
• For price regulations to be effective, enforcement is essential as well as sufficient national capacity to monitor prices in the market.

GUIDELINES FOR INSULIN DONATIONS IN LOW- AND MIDDLE-INCOME COUNTRIES

Hans V Hogerzeil, MD, PhD, FRCP Ed

Goningen University, The Netherlands

Short description of the tool

This document contains a short description of major insulin
donation programmes, with their impact on health and public health. It presents practical recommendations, supported with summary text on
justification and practical implications of each.
The document also presents a ten-step plan to phase out insulin donation programme in LMICs, working towards a sustainable national programme
of universal access to insulin.

Who is this tool for?

The document is directed towards agencies involved in insulin donations, national diabetes programmes, and national health policy makers.

How is it used?
Some recommendations are for immediate application (e.g. those on the quality of insulin donations, arguments for the continuation of donation
programmes, and practical advice on improved reporting), and are especially relevant for donors and national diabetes programmes. The
recommendations on a gradual transition to a sustainable national system are also directed to national health policy makers.

Main recommendations
1. Donor agencies should ensure that all donations of medicines, diagnostics and equipment follow the WHO Guidelines for Medicine Donations
2. Donor agencies should report regularly on programme targets, the number of people living with diabetes covered, health outcomes, key health
system data, the role of partners, and project financing
3. National diabetes programmes and donor agencies should plan well in advance the transition of recipients of donated insulin beyond their
eligibility to programme support. This transition should be supported with specific investments and programme activities; links with existing insulin
discount programmes should be strengthened
4. Donor-supported programmes such as LFAC and CDiC should be continued and expanded in countries in need, as long as the diagnosis and
treatment of type 1 diabetes and its complications are not yet included in national health insurance schemes
5. Ten steps to phase out an insulin donation programme (see guidelines)

THE ROAD TO FREE INSULIN: COUNTRY CASE

STUDIES
Multiple authors

Short description of the tool

These case studies contain information on the national health system, diabetes epidemiology, and the provision of free insulin to people living with
diabetes. Challenges and lessons learnt are identified, leading to some practical recommendations.

Who is this tool for?

These documents are directed towards national diabetes programme managers and senior health policymakers, including national organisations
dealing with financing health care and medical supplies.

How is it used?
The document can be used to learn about successful approaches in other LMICs in the supply of insulin as part of universal health care coverage,
with emphasis on lessons learnt. Some ideas and experiences from this document may be used when designing or improving national diabetes
programmes.

THE ROAD TO FREE INSULIN: CASE STUDY KEY

POINTS
Key points from Guyana
• Strong constitutional basis, with free health care for
all citizens; political will
• Healthcare costs covered for an estimated 80
percent of the population
• No import duties on human insulin
• National register of young diabetes patients
• No analogues on the EML, no analogues
supplied/reimbursed
• Person-centered approach; 50 strips per months reimbursed for type 1 diabetes
• Economic growth (4.7% per year in 2005-2014; 3.1-3.3% in 2015-2016) has helped
Key points from Ecuador
• The situation in Ecuador has much improved since 2000, linked to the new constitution of
2004 with a government commitment towards free medicines for all
• The national EML does not contain any insulin analogues, because the committee did not
consider them cost-effective; analogues are not supplied or reimbursed
• The national diabetes policy is more focused on
type 2 diabetes than on type 1 diabetes
• There are insufficient funds for the
supply/reimbursement of diagnostic
Key points from Kyrgyzstan
• Free supply of insulin through central procurement
• Many challenges have been identified, including:
o Insufficient funds for all needed supplies, including diagnostics
o Too many analogues supplied; not always cost-effective
o Distribution challenges
o Too much reliance on diabetologists, which are only in the cities
o Insufficient training of primary health care workers and people living with diabetes

Key points from Lebanon

• Free medicines for NCDs, including diabetes; strong emphasis on equity
• NCD care through network of 200 accredited primary health care (PHC) centres, some run
by NGOs
• National insulin coordinator to verify insulin is free; hotline for queries and complaints
• Good separation of various procurement committees (e.g. Tender Committee, Contract
specification committee, Reception Committee, and a committee to estimate needs and
costs) which reduces vulnerability for corruption
• Challenges identified include: weak forecasting of needs, lack of diagnostic capacity, lack
of education for people with diabetes, inadequate assessments by physicians of glycemic
control

Key points from Thailand

• Very good national data on diabetes epidemiology
• Universal coverage of insulin since 2002
• Nine different insulin types in 28 forms are supplied (including analogues and pens)
• Availability of national clinical guidelines
• Challenges are the lack of information on insulin use, waste by patients, and the need for
more diabetes educators

THE FAIR PRICE OF ANALOGUE INSULIN WHEN COMPARED

AGAINST HUMAN INSULIN
Jing Luo, MD
Instructor in medicine, Program on regulation, therapeutics, and law
(PORTAL)
Harvard Medical School, Brigham and Womens Hospital

Short description of the tool

This document contains a systematic literature review of published cost-effectiveness
studies comparing analogues with human insulin, with much detailed information on recent
studies, reviews and meta-analyses. In a separate section, a method is presented to
estimate a fair price for analogue insulin that reflects it marginal benefits over human
insulin.

Who is this tool for?

The document is directed towards health policy makers and reimbursement authorities in
LMICs.

How is it used?
The information can be used to support decisions regarding the reimbursement of analogue
insulin products, and at which price level.
Key points from the tool
• 20/24 (83%) cost-effectiveness analyses were conducted in North America and Europe;
there was large variability in study design, comparators, clinical outcome measures and
medicine prices.
• 22/24 (92%) of studies were sponsored by the pharmaceutical industry. All these studies
conclude that analogues are more cost-effective than human insulin.
• The only independent studies were from Canada and Thailand. These two studies
concluded that analogues are not more cost-effective than human insulin (Thailand) or
mostly not cost-effective (Canada).
• The method to estimate a fair price of insulin analogues needs more work; such value-
based pricing methods should also consider the clinical and political context, budget impact,
opportunity costs, and fairness/equity concerns.

Main recommendations
1. Policymakers in LMICs should choose long-acting analogues only when their prices are
comparable or slightly higher than human insulins. Data available from published modeling
studies suggest that the cost effectiveness of an analogue insulin is sensitive to its procured
price. Long-acting analogues are highly unlikely to be cost effective in LMICs when their
price is higher than human insulin.
2. Policymakers in LMICs should choose rapid-acting analogues only for people with type 2
diabetes when the price difference between the analogue and human insulin is negligible.
3. More independent studies are needed on the comparative cost-effectiveness of analogues
and human insulin in low-resource settings.

COSTING MODEL FOR UNIVERSAL DIABETES CARE

Veronika Wirtz
Boston University
Corrina Moucheraud
UCLA

Short description of the tool

This Excel Calculator estimates the total annual direct medical cost of providing clinical care
for people with diabetes mellitus for LMIC. It is based on prevalence estimates for diabetes
(types 1 and 2) and associated complications; normative estimates and values from the
literature about adherence to recommended treatment guidelines; and price information for
routine care and for treatment of complications.

Who is this tool for?

The tool is directed towards policy makers, health system financiers and other key
stakeholders about the appropriate degree of financing necessary to fully address the
diagnosis and treatment of diabetes in a given country context.

How is it used?
The tool estimates of the cost of diabetes care based on default values from high-income
settings, using pre-populated model parameters. However, the user can opt to enter new
(country-specific) data for certain parameters, including epidemiologic information and unit
prices.

Key points from the tool

• The tool presents a normative perspective: it does not aim to reflect a current situation but
rather to estimate the total direct medical costs if a country were to provide comprehensive
diabetes care at-scale.
• The tool allows for all underlying data to be adapted to real or assumed national values; as
such it is also useful to create various “what-if” scenarios.