Delinkage of the cost of research and development from drug prices

James Love, Director of Knowledge Ecology International

This was a fascinating talk that proposed an alternative model for R+D of new drugs that would reduce the cost of new drugs and improve access for all.

Love outlines how the current drug patent and monopoly for funding the R+D of new drugs has many challenges. Pharmaceutical companies invariably set prices for maximum profitability and costs have risen dramatically even over the past 10 years. The current trajectory means that high and middle-income countries will likely limit access and impose restrictions on those who receive these treatments, and resource-limited settings will face further inequities.

Love proposes an alternative model that funds R+D by “delinkage” of the cost or R+D of new drugs, from the final price of the product.  Alternative funding models for R+D have been proposed; drug research grants and contracts, R+D subsidies, incentives and innovation prize funds.

Some of the above initiatives already exist. There are NIH and EU framework grants, R+D subsidies such as the Orphan Drug tax-credits which are funds available for R+D on drugs for rare diseases (apparently 47% of new US drug approvals in 2015 fell under this model).

Love proposes expansion of current incentives, and progressively switching from the current system of monopolies to alternative models of funding. Progressive delinkage mechanisms could be introduced by governments over time that sequentially move prices closer to the marginal cost of production of the drug.

Love talked about the $15 billion spent on HIV drugs in the US annually with the return of on average one new HIV drug per year. Recently Bernie Sanders in his US election campaign proposed that $3 billion of this money be set aside to fund R+D for new HIV drugs and at the same time eliminate monopolies. He also advocated setting aside funds to reward scientists and researchers who contributed to the development of a drug via open source platforms. 

There seems to be growing support for Love’s model with many seeing the current system as unfair and ridiculously expensive. Apparently several members of the European parliament have expressed interest in the delinkage model, the Human Rights Council has asked states to support the principles of delinkage, India and the World Health Assembly have endorsed the model, the CEO of GSK has endorsed the delinkage model in the context of expensive drugs for rare diseases and several companies have endorsed it for the development of new antibiotics.

This issue has repercussions the world over, and is pertinent at a conference being hosted in sub-Saharan Africa that addresses the HIV and viral Hepatitis epidemics. While we come from a relatively privileged position in Australia, we do face shortages in provision of access to many of the new cancer medications, and one wonders how our health budget will fund the escalating pharmaceutical costs in the future.  This talk outlined an elegant alternative model of funding R+D that would be more equitable and allow universal access to new drugs for all.

 

With the rapid scale up of access to ART and with countries working towards the 90-90-90 and 2030 targets, this session seemed very pertinent in addressing the final tier of the cascade – that 90% of those on treatment should have an undetectable viral load. Meg Doherty from WHO discussed that this is particularly important in settings where access to viral load and drug resistance testing is limited.

Several low and middle income countries have reported levels of HIVDR at or above 10% in ART naive patients and up to 37% in those restarting ART with prior exposure to ART. *

The WHO speaker cautioned that a “one size fits all approach” would be a mistake and this was certainly evidence by presentations from certain countries with varying resistance rates. However access to viral load, not to mind genotypic resistance testing is lacking in many low and middle income resource countries and each country needs to collect this data to guide and tailor its own response.

Modeling suggests that the cost of inaction is a costly price to pay with increased morbidity and mortality, increased transmitted resistance, increased program costs with second and third line ARVs and increases in new infection rates.

WHO recommends that each country should have a HIVDR surveillance strategy that is based on 1) Early Warning Indicators which essentially reflect the quality of care of the program and include data on prescribing practices, loss to follow-up, ARV supply continuity, viral load etc, 2) National surveys of pre-treatment resistance, 3) National surveys of acquired drug resistance, and 4) Nationally representative surveys that measure drug resistance in <18month olds.

Other interesting comments from panel members at the session emphasised the importance of monitoring drug resistance in pregnant women returning to care with PMTCT option B+ and also in children and adolescents who have lower viral load suppression rates than with adults.

The Global Fund panelist talked about the important implications of HIVDR rates in reaching other targets such as 90% of people who have need of PrEP having access to it, and HIVDR rates being important for effective PrEP.

Dr Anna Flavia presented some of the drug resistant data from Brazil where pre-treatment Efavirenz resistance rates are 7%. This has prompted discussions about whether the national program should recommend routine resistance testing prior to ART initiation, or whether the country simply switch to including Dolutegravir in the first line regimen. All cost benefit analyses favour the switch to Dolutegravir rather than performing resistance testing on all commencing treatment.

The take home message from this presentation was that drug resistance is rising and if the target of ending AIDS by 2030 is to be achieved, then monitoring and responding to HIVDR will be a critical element and that each country is called to act and collect more and better data in order to tailor their response in terms of thinking about switching ART regimens and quality improvements to their HIV programs.

*The WHO draft of the Global Action Plan on Drug Resistance (2017-2021)