Table 1 Studies of trade agreements

EU trade agreements

Grootendorst and Hollis 2011 [22]

Prospective modelling to determine how proposed provisions in CETA would affect public and private health care costs

CETA’s TRIPS-plus IP provisions would delay the market entry of generics and increase Canada’s annual pharmaceutical expenditure. Payers – consumers, businesses, unions and government insurers – would face substantially higher drug costs as exclusivity is extended on top-selling prescription drugs, with the annual increase in costs likely to be in the range of $C2.8 billion per year.

Lexchin 2014 [23]

Prospective modelling study to determine the impact of the 3 settings in CETA - patent term restoration, data protection, rights of appeal on the cost of prescription drugs in Canada

Using 2010 data, the CETA data exclusivity provisions would have increased the average duration of market exclusivity for patented drugs by 358.4 days, or 0.98 years, which would bring an additional yearly cost of $C795 million, or 6.2% of the total annual cost of patented drugs. If data exclusivity were extended to non-innovative drugs, the average delay would increase by 741 days, or 2.03 years, which represents an additional yearly cost of $C1,645 million, or 12.9% of total costs of patented drugs.

Beall et al.^a 2019 [24]

Prospective modelling study to evaluate the total combined impact of prolonging market protection by extending competition-blocking patent and data exclusivity terms implicit in the Canada, United States, and Mexico Trade Agreement and the Comprehensive Economic and Trade Agreement with the European Union.

The collective impact of these policy changes would be to extend the regulatory protection period for new drugs from an average of 10.0 years to 11.1 years. An 11% increase equates to an average of $C410 million annually (with a minimum estimate of $C40 million and a maximum of $C1.4 billion).

IFARMA HAI EU 2009- Andean FTA (Peru) [22]

Prospective scenario planning used to evaluate the foreseen impact on access to medicines in Peru from the IP measures (data exclusivity and patent term extensions through Supplementary Protection Certificates (SPCs)) proposed by the European Union as part of the EU- Andean FTA.

Estimates that these two measures would increase Peru’s total pharmaceutical expenditure in 2025 by $US 459 million if current consumption is maintained. Consumption decrease would be caused by the result of an 11% increase in the number of API protected, which in turn would lead to a 26% price increase. Implementing Article 9.3 SPC measures (thus extending the effective patent period by 4 years), would lead to a $US 159 million increase in pharmaceutical expenditure in 2025. At the same time, implementing the proposed 10-year test data exclusivity period would lead to an increase of more than $US 300 million USD in 2025 expenditure.

IFARMA/HAI EU 2009- Andean FTA (Columbia) [23]

Prospective scenario planning used to evaluate the foreseen impact on access to medicines in Colombia from the IP measures proposed by the European Union as part of the EU-Andean FTA. Specifically assesses the impact of increasing the effective duration of pharmaceutical patents and test data protection.

It is estimated that the introduction of the two measures on data exclusivity and SPC would lead to an increase of $US756 million in Colombia’s total pharmaceutical expenditure in 2025, and at the same time, a decrease in consumption of 10%. The consumption decrease is caused by an 8% increase in the number of IPR protected products, which in turn would produce a 16% price increase.

US trade agreements

Yoongthong 2015 [25]

Prospective modelling study to estimating impact of TRIPS-plus measures on the Thailand economy through consumer welfare estimate.

The enforcement of proposed TRIPS-plus would result in a substantial loss to the Thai economy, ranging between 30 billion baht and 136 billion baht, within a 10-year period from 2012 to 2021.

Kessomboon et al. 2010 [26]

Prospective scenario modelling of the impact of the TRIPS-plus provisions set out by the Thai-US FTA proposal – a 10-year patent term extension, 10-year data exclusivity and patent linkage leading to a 5-year delay in generic entry. It used the Model of Impact of Changes in Intellectual Property Rights (MICIPR) framework.

The findings for all scenarios demonstrated a negative impact on the pharmaceutical market, particularly increasing drug expenditures, reducing access to medicines, and shrinking the domestic pharmaceutical industry.

Comparison of the single provisions of the US proposal revealed the 10-year patent extension scenario would have the greatest negative impact: a 32% increase in the price index for medicines; increased spending on medicines to approximately US$11,191 million; the domestic industry would lose US$3370 million. The impact of all three provisions combined, over the next 20 years (2027) would be: 67% of medicine prices would increase: pharmaceutical expenditures would increase to US$23,595 million; the domestic industry could lose US$9000 million.

Akaleephan et al. 2009 [27]

Prospective modelling study to estimate the impact of market exclusivity extension on the price of medicines under the proposed TRIPS-plus US-FTA model and to estimate the current potential cost saving loss and accessibility to medicines.

In 2003, the availability of generics would help to save 104.5% of actual expense and accessibility would increase by 53.6%. The extension of market exclusivity was estimated to lead to a cumulative potential expense of $US 6.2 million for the first year rising to $US 5215.8 million in the tenth year.

Malpani 2009 [28]

Retrospective analysis of the impact of TRIPS-plus measures on affordability and availability of medicines in Jordan. Evaluates the claims of the benefits of TRIPS-plus rules for Jordan.

Data exclusivity prevents generic competition for 79% of medicines launched by 21 multinational pharmaceutical companies between 2001 and 2006. Additional expenditures for medicines with no generic competitor, as a result of enforcement of data exclusivity, were between $US6.3 m and $US22.04 m.

Abbott et al. 2019 [26]

Retrospective analysis of the impact of Jordan’s increased IP protection, as a result of WTO accession and the US-Jordan FTA, on access to medicines. Quantifies the impact from delaying the entry of generics due to IP protections on the private retail market.

When assessing originator medicines that were marketed in both 1999 and 2004, and for which there were generic equivalents, the weighted average price of originator medicines increased while the weighted average price of equivalent generic medicines decreased. Delayed market entry of generics due to enhanced IP protection is estimated to have cost Jordanian private consumers approximately $US18 million in 2004. After adjusting for increased sales volume and inflation, from 1999 to 2004 there was a 17% increase in total annual expenditure for medicines in Jordan.

Oh and Kim 2012 [29]

Prospective study to estimate the impact of IP measures in the KORUS trade agreement on market size and welfare on the Korean economy.

When KORUS is finalized, estimated producers’ annual sales loss and consumers’ annual loss will be 0.223 and 0.155% of the total market size, respectively, due to patent extensions compensating for delayed patent registration. In the case of linking original patents to generic drug approval, producers’ annual sales loss and consumers’ annual loss will be 0.789 and 0.546% of total market size, respectively. When the market size of original drugs and generics is assumed to be $US3.0 billion, total welfare loss (the sum of producer’s loss and consumer’s loss) will be $US11.34 million due to delayed registration and $US 40.03 million due to patent linkage.

Son 2020 [30]

A prospective statistical modelling study to capture the availability of new medicines, measure drug lags for new medicines, and to demonstrate the effect of the KORUS FTA on the timely availability of new medicines in the Korean market.

The KORUS FTA does not increase the availability of new medicines or shorten the drug lag of new medicines. However, the presence of the manufacturer in Korea was significantly related to the availability and drug lag in the Korean market. It is noteworthy that the presence of the manufacturer, which is a kind of by-product of free trade in pharmaceuticals, affected drug lag.

Beall et al.^a 2019 [24]

Prospective modelling study to evaluate the total combined impact of prolonged periods of market protection by extending competition-blocking patent and data exclusivity terms implicit in the Canada, United States, and Mexico Trade Agreement and the Comprehensive Economic and Trade Agreement with the European Union.

The collective impact of these policy changes will be to extend the regulatory protection period for new drugs from an average of 10.0 years to 11.1 years. An 11% increase equated to an average of $US 410 million annually (with a minimum estimate of $US 40 million and a maximum of $US 1.4 billion).

Lexchin 2019 [31]

Prospective statistical modelling to investigate the effect the renegotiated North American Free Trade Agreement’s (NAFTA) increase in data protection for biologics from 8 to 10 years on drug spending in Canada.

Depending on how much of the market is captured by biologic competitors and how strong the patents are, lost savings from data protection extension could range from $US 0 to $US 305.8 million. One biologic competitor currently on the market could theoretically have been affected by an increase in data protection. Increased data protection would have had minor effects on products that have already lost data protection.

Parliamentary Budget Office 2019 [32]

Prospective modelling to estimate the potential cost of the extended term of data protection. It defines that cost as the additional expenditures on originator prescription biologics relative to their potential competitors.

In 2015, some 16 biologics worth $US 422.4 million in prescription sales had data protection expiring between 2015 and 2023. By 2023, all drugs with data protection in 2015 would have lost it, were it not for CUSMA. On average, $US52.8 million worth of sales would have lost data protection annually over that period ($US422.4 million divided by eight years). Effectively, for those drugs whose primary patent expires before the extended data protection, CUSMA would have delayed the entry of lower cost biosimilars that would have competed for market share. PBO assumed that the discount from a biosimilar would be 30% and that biosimilars would affect sales in 75% of the market of the biologics losing data protection. As a result of the delay, the annual average increase in drug costs would amount to $US11.9 million per year. Doubling this number to account for the fact that it is a two-year extension produces an annual average increase in costs of $US23.8 million between 2015 and 2023.

Shaffer and Brenner 2009 [33]

Retrospective study of effect of data exclusivity in CAFTA on access to medicines in Guatemala

CAFTA’s data exclusivity and patent rules as implemented in Guatemala through domestic law and regulation are limiting access to some more affordable generic drugs. Some drugs would become open for generic competition in the US (where they were first launched) before Guatemala. Some generic competitors denied entry to market, or removed from market, in Guatemala.

Trachtenberg et al. 2020 [34]

Retrospective study to measure the strength of IP provisions in Chile’s FTAs and to examine the extent to which FTAs with strong IP provisions impact the volume, unit value and overall value of imported biologic medicines into Chile.

FTAs with more stringent IP provisions increase both the volume and the unit value of imported biologics, suggesting greater availability of imported biologics at a higher price.

Moir et al. 2018 [35]

Prospective modelling to estimate the potential impact of the TPP on cost and thus access to HIV treatment in Vietnam.

At current funding levels 82% of Vietnam’s eligible people living with HIV would receive ARVs if TRIPS legal flexibilities were fully utilised, while as few as 30% may have access to ARVs under the TPP Agreement – more than halving the proportion currently treated.

Bollyky 2016 [36]

Prospective modelling study to determine whether trade deals with the US have increased medicine prices, spending on medicines or caused a shift away from lower cost generics.

For countries with trade deals with the USA: national pharmaceutical spending as a share of total health expenditure has not increased; growth in per capita pharmaceutical spending has not increased in comparison with comparator countries; consumption of pharmaceuticals has not increased; proportions of branded vs generic drugs consumed has not increased; and average price of off-patent originator medicines launched before and after US trade deals has not increased. The study does not take into account that many of the TRIPS-plus provisions in the trade agreements did not come into effect during the period studied.