KNOWLEDGE PORTAL
on innovation and access to medicines
RESEARCH GAPS
* Last updated April 2019
One of the objectives of the Knowledge Network for Innovation and Access to Medicines is to identify and help to fill important research gaps. This synthesized list of identified gaps was drawn from a combination of data sources gathered in 2018-19: literature reviews synthesizing the existing knowledge base, in-person research meetings, and expert opinion. The list is inclusive at this stage: it includes topics that at least some stakeholders felt merited further work beyond existing research. Under each topic we have linked to further information on this website on relevant literature and/or data sources, recognizing that these resources only partially address the research gaps.
The list may be of use to researchers, students, research funders and others who can help to fill the gaps. In addition, the list should be considered a living draft – we welcome information regarding existing research or new studies that can help to address these gaps or identify additional ones.
THEMES
PRICING
1. Mapping of the actual availability on the ground and actual prices of all priority health technologies including medicines, diagnostics and medical devices.
2. International databases of drug prices – both list prices and real transacted prices (See a selection of sources).
a. Additional empirical studies on the impact, benefit and transaction cost of pooled procurement on drug prices,
including mechanisms at international, regional and national levels, particularly in developing countries;
b. Better understanding of the conditions under which pooled procurement is most effective;
c. Further research to understand the specific needs of middle-income countries (MICs) in pooled procurement
mechanisms;
d. Data to compare quality, quantity and prices of drugs supplied inside vs. outside of pooled procurement institutions (e.g. Global Fund and Global Drug Facility - GDF).
4. Better understanding of the impact of regulatory standards on in-country availability of originators and generics, particularly biologics and biosimilars.
5. Structural causes of shortages, and the role that prices play, especially in comparison to other causal factors.
6. Relationship between price transparency and prices in different countries.
7. Affordability:
a. Methods to measure and assess financial hardship (or resource benchmarks) for different types of payers, including both individuals/households and organizations (e.g. private or public insurers, governments);
b. Use of competition policy to regulate pricing, including how to determine a line between a fair and excessive price;
c. Research on benchmarks and/or fiscal space for government spending on health: existing and suggested ways to determine how much of a country’s health resources should (or should not) be spent on medicines.
8. Donation programmes:
a. Impact of drug donations on medicines access, prices and on generics industry;
b. Sustainability of donation programs, especially in non-emergency settings and for diseases with long-term treatment periods (e.g. HIV/AIDS, TB, etc.);
c. Tracking of product donation history of different pharmaceutical companies over time (in emergency and non-
emergency contexts);
d. Better understanding of tax benefits for pharmaceutical companies that make donations.
9. Differential or tiered pricing:
a. The degree to which medicines prices correlate to different income levels across low, middle and high-income countries;
b. The determinants of price differentials and country groupings in tiered pricing policies (e.g. the methods by which such prices are established) ;
c. The impact of tiered pricing on the price of first entry generics;
d. Analysis of the feasibility and/or application of intra-country differential pricing;
e. Analysis of reference pricing policies and how they impact international differential pricing.
10. Health technology assessment:
a. More studies analyzing use or feasibility of HTA in low- or middle-income countries
b. Analyses of HTA as an input to medicines pricing and incentive for innovation.
11. Parallel import or trade:
a. Analysis of estimated or potential savings of parallel trade in medicines and impact on prices, particularly for countries outside of the EU;
b. Further analysis of the distribution of economic benefits from parallel trade (patients, distributors, etc.).
12. Price regulation or control:
a. Impact of different price regulation policies on prices and availability of medicines;
b. Further research on efficacy of current or potential price control mechanisms in relatively small markets, e.g. LMICs or HICs with small populations.
13. Mark-ups, taxes, supply-chain costs:
a. More data and analysis from different countries on the impact of increases or decreases of taxes, mark-ups, and other costs that accrue through the supply chain on the final price of a medicine;
b. Additional research to determine what level of mark-ups can support a viable supply chain while maximizing affordability.
INTELLECTUAL PROPERTY
1. Information on the patent status of medicines, diagnostics and other medical devices that are a public health priority, beyond the relatively well-documented medicines for HIV, tuberculosis and hepatitis C (See a selection of data sources here.)
2. Impact and implementation of TRIPS in national IP laws and policies:
a. Empirical evidence regarding the relationship between domestic IP policies and other economic variables such as levels of foreign direct investment, imports/exports, economic growth, or innovative activity;
b. Empirical evidence of direct and indirect effects of issuing compulsory licenses and use of other TRIPS flexibilities (e.g. strict patentability criteria, patent oppositions). Direct effects may include changes in medicines prices or access. Indirect effects may include those on the broader economy, trade relations, political relations, and innovation;
c. Analyses of factors that facilitate or impede the use of TRIPS flexibilities;
d. Empirical evidence on the relationship between patent protection and “rates” (e.g. numbers of new products) and “direction” (e.g. diseases targeted) of pharmaceutical innovation;
e. Information on how patentability standards are translated into patent examination manuals for implementation by patent offices, and empirical evidence of application of patentability standards in practice;
f. Data on Least Developed Countries’ implementation of IP laws and policies, in light of the TRIPS extension for LDCs until 2033 for pharmaceuticals (and until 2022 for TRIPS in general).
3. Impact and implementation of TRIPS-Plus measures (e.g. patent term extensions, data exclusivity) in and outside trade agreements:
a. Further mapping of free trade agreements (FTAs) and their medicines-related provisions, especially beyond intellectual property chapters (e.g. enforcement and investment chapters);
b. Methodologies and empirical evidence on the actual or projected impact of TRIPS-plus measures, on medicines prices, registration, patents and availability;
c. Empirical evidence regarding the positive and negative economic impacts of FTAs beyond pharmaceuticals.
4. Mapping of agreements between national and regional patent offices for granting of pharmaceutical patents, in particular, agreements between patent offices for automatic revalidation of patents granted by the European Patent Office.
a. Mapping of terms and conditions in voluntary licenses, including covered medicines, countries, timeframes for negotiation, period of licenses, provisions for use of TRIPS flexibilities, criteria for licensees, and suppliers in and outside of voluntary licenses;
b. Comparison between bilateral (e.g. patent-holding firm to licensees) and multilateral (e.g. Medicines Patent Pool, patent-holders to 3rd party to licensees) voluntary licenses;
c. Further research on changes in prices and availability of medicines under voluntary license and other policies (e.g. no license, compulsory license, narrower or wider voluntary licenses, tiered pricing, donations);
d. Further analysis of access concerns in voluntary licenses, such as implications for middle-income countries and for the generics industry;
e. Analysis of operation and costs of patent pools.
6. Analyses of the patentability of newer technologies such as biologics, technologies developed by artificial intelligence, and technologies that may be considered “methods of treatment” such as CAR-T (chimeric antigen receptor T-cell) immunotherapy.
7. Improved understanding of the concept of trade secrets and their use in the pharmaceutical sector.
INNOVATION/R&D
1. More in-depth mapping of actors and funding flows for biomedical R&D, including both traditional and non-traditional actors and sources of financing.
2. Clearer conceptualization and measurement of “risk” and probabilities of success in the pharmaceutical R&D process.
3. Information on specific medicines, including the history of their development, such as:
a. Cost of R&D for specific health technologies, including financial and non-financial contributions of academia, governments, philanthropies and commercial firms. Cost estimates should include direct funding (e.g. grants, investments) as well as public subsidies and tax incentives;
b. Evidence on the contribution of public funding of R&D of health technologies, and/or to the underlying basic science and/or platform technologies.
4. Empirical evidence of alternate business models of R&D such as:
a. Case studies of successful and unsuccessful drug development carried out by non-commercial actors, including the public sector and product-development partnerships, particularly outside the US and Europe;
b. Implementation of full or partial delinkage (rewarding innovation separately from prices).
5. Information on how universities are out-licensing their research, including to whom and on what terms and conditions, and the availability and prices of licensed products.
a. Analysis regarding the extent to which PRVs increase R&D efforts over business-as-usual in targeted diseases, and whether or how they shape R&D decision-making;
b. Research on the extent to which products covered by PRVs are made available, manufactured and distributed to the public, and at what price.
7. Product Development Partnerships:
a. Updated analysis of the successes and failures of PDPs, especially on new chemical entities developed by PDPs;
b. Operational costs of PDPs, in general, and costs specific to PDP R&D activities;
c. Analysis of intellectual property and access policies and practices of PDPs;
d. More information on the governance structure and processes of PDPs and the impact it can have on their decisions.
8. Analysis of impact of patent pools on biomedical R&D (see further questions on voluntary licenses for access under “Pricing”)
9. Advanced Market Commitments:
a. Study of effectiveness of AMCs in driving early-stage and/or late-stage R&D for vaccines and other pharmaceutical products;
b. Analysis of AMC’s ability to incentivize supplier competition and provide security of supply.
10. Public funding of health R&D:
a. Information on national policies for innovation and public R&D investment, particularly in advanced economies with established R&D activity;
b. More information on public spending in health R&D beyond the US and EU;
c. Information on any conditions attached to public funding of R&D (e.g. relating to affordability or availability of end products), including in laws, policies or contracts, and compliance with or enforcement of such conditions.
OTHER TOPICS
1. Industry and market structure, such as:
a. Impact of mergers and acquisitions on R&D investments, productivity and prices;
b. Mapping of sources of active pharmaceutical ingredients and analysis of implications of various degrees of market concentration among suppliers for prices and security of supply;
c. Mapping of producers of generics and biosimilars, including when owned by originator firms;
d. Analysis of benefits and risks of agreements for technology transfer between firms, including pro- and anti-competitive effects;
e. Impact and feasibility of local production.
2. Competition law and its potential impact on innovation processes, market structure and prices.
3. Further analysis on the role of investors and financial markets in shaping R&D decisions, influencing the structure of the pharmaceutical industry, and affecting access.
4. Political analysis (in addition to legal and economic analysis): how policies are influenced by lobbying and other political tools.
5. Newer technologies: Need for improved understanding of innovation and access issues (e.g. manufacturing, regulation and IP) for health technologies beyond small-molecule drugs, in particular biologics, diagnostics, medical devices and emerging technologies such as gene editing, immunotherapy, nanotechnology, artificial intelligence, and others.
6. Horizon scanning: looking at phase 3 clinical trials for all health technologies to conduct policy research and analysis on the most promising ones before they enter the market.
