Rotavirus vaccination has been a global health success story. In 2008, RotaTeq® received
World Health Organization (WHO) prequalification, which was followed by the prequalification
of ROTARIX® in 2009 [1]. Over the following decade, these two vaccines were introduced
in around 100 countries’ immunization programs and have contributed to significant
declines of the global rotavirus disease burden [2], [3], [4], [5]. Then, in 2018,
two new rotavirus vaccines made in India, ROTAVAC® and ROTASIIL®, also received WHO
prequalification. This was a landmark achievement for the rotavirus community, as
it expands product choice and has the potential to help lower prices, mitigate supply
concerns, and enhance rotavirus vaccine impact around the world through the broader
use of rotavirus vaccines, particularly in low- and middle-income countries. However,
having a range of rotavirus vaccine options with heterogeneous characteristics including
different presentations, dosing schedules, and prices can also present decision-makers
with more complex choices in selecting a vaccine product. This challenge is likely
most pressing in countries where rotavirus burden is highest, resources are particularly
constrained, and the feasibility of fully assessing and comparing all options is most
limited.
Gavi, the Vaccine Alliance, and international partners recognized this challenge and
have been working to compile information to help country decision-makers evaluate
the available rotavirus vaccine products [1]. These resources include details on the
vaccines’ efficacy, effectiveness, safety, cost, cost-effectiveness, storage and transportation
requirements, and other programmatic considerations. Despite considerable effort,
decision-making remains challenging for those seeking to optimize rotavirus vaccine
product choices. Reasons for this difficulty may include the breadth and depth of
the available information, challenges in prioritizing different product attributes,
the dynamic nature of the rotavirus vaccine market, the lack of guidance on when and
how to consider product switches and in some cases, interpretation of the available
information.
Cost and cost-effectiveness are important considerations in making rotavirus vaccine
product choices; they also exemplify some of the challenges that countries face. A
recent publication in this journal (written by the authors of this commentary) compared
the costs and cost-effectiveness of three alternative rotavirus vaccines in three
countries supported by Gavi (Bangladesh, Ghana, and Malawi), assuming common efficacy
in each country across the three products [6]. The analysis concluded that all three
rotavirus vaccines examined were likely to be cost-effective in each country compared
to no vaccination. In addition, one of the products was consistently the least costly
and most cost-effective of the three examined (Table 1). While this finding was consistent
across countries, it was also reported as “sensitive to relatively modest changes”
in vaccine prices or vaccine delivery costs. In short, the previously published analysis
showed that: (1) all three vaccines were likely cost-effective compared to no vaccination,
(2) ROTARIX was the least costly and most cost-effective product in the three examined
Gavi-supported countries, and (3) the results were consistent but sensitive to small
changes in input values, in particular where there is significant uncertainty (e.g.
vaccine prices or vaccine delivery costs).
Table 1
Cost and cost-effectiveness by country and vaccine product, initial analysis.
Bangladesh
Ghana
Malawi
Cost per DALY* averted (country perspective, with Gavi subsidy)
$61 (ROTARIX);$153 (ROTAVAC);$216 (ROTASIIL)
$230 (ROTARIX);$283 (ROTAVAC);$358 (ROTASIIL)
$7 (ROTARIX);$38 (ROTAVAC);$32 (ROTASIIL)
Total country cost of vaccination program with Gavi subsidy**
$41.6 M (ROTARIX);$53.5 M (ROTAVAC); $61.7 M (ROTASIIL)
$67.9 M (ROTARIX);$81.5 M (ROTAVAC); $100.5 M (ROTASIIL)
$10.2 M (ROTARIX); $14.5 M (ROTAVAC); $13.5 M (ROTASIIL)
Least costly and most cost-effective product
ROTARIX
ROTARIX
ROTARIX
*
Disability adjusted life year.
**
All cost and cost-effectiveness estimates in this article incorporate wastage rates
as previously reported [6].
In less than a year since the publication of this cost-effectiveness analysis, the
reported prices for all three vaccines have changed, some dramatically. In addition,
new information is emerging on the delivery costs (e.g. administration, cold chain,
training) for the new rotavirus vaccines. While the initial analysis remains an accurate
portrayal of the world at that time and illustrated key uncertainties that would influence
findings, the results no longer accurately reflect the choices now facing these three
countries. In fact, if the initial analysis had been undertaken with today’s best
information, all vaccines would remain cost-effective compared to no vaccination,
but the rank order might now be very different.
Table 2 illustrates two additional scenarios using the previously reported modelling
approach and data inputs [6]. We again assume common efficacy values across products
in each country as we do not believe there is yet enough evidence to differentiate
by product. Scenario 1 incorporates updated pricing data for ROTAVAC (five-dose vial,
frozen presentation) and ROTASIIL (two-dose vial, lyophilized presentation) and emerging
information from a single setting outside of our examined countries which suggests
that delivery costs for ROTAVAC are lower than those for ROTARIX by approximately
$0.30, primarily due to lower cold chain costs [1], [7]. Scenario 2 incorporates these
changes and assumes that emerging findings on ROTAVAC delivery costs could also apply
to ROTASIIL. While there are some data to support these scenarios, evidence remains
limited. As such, Table 2 is meant to illustrate the sensitivity of the results to
relatively small changes to input parameters rather than a clear argument for a single,
economically preferred product across these countries.
Table 2
Cost and cost-effectiveness by country and vaccine product, subsequent analysis.
Bangladesh
Ghana
Malawi
Scenario 1: Updated vaccine prices; applying lower delivery costs for ROTAVAC
Cost per DALY averted (country perspective, with Gavi subsidy)
$76 (ROTARIX);Cost-saving (ROTAVAC);$126 (ROTASIIL)
$249 (ROTARIX);$220 (ROTAVAC);$251 (ROTASIIL)
$7 (ROTARIX);Cost-saving (ROTAVAC);$32 (ROTASIIL)
Total country cost of vaccination program with Gavi subsidy
$43.6 M (ROTARIX);$29.5 M (ROTAVAC); $50.0 M (ROTASIIL)
$72.6 M (ROTARIX);$65.3 M (ROTAVAC); $73.3 M (ROTASIIL)
$10.2 M (ROTARIX);$7.3 M (ROTAVAC); $13.5 M (ROTASIIL)
Least costly and most cost-effective product
ROTAVAC
ROTAVAC
ROTAVAC
Scenario 2: Updated vaccine prices; applying lower delivery costs for ROTAVAC and
ROTASIIL
Cost per DALY averted (country perspective, with Gavi subsidy)
$76 (ROTARIX);Cost-saving (ROTAVAC);Cost-saving (ROTASIIL)
$249 (ROTARIX);$220 (ROTAVAC);$207 (ROTASIIL)
$7 (ROTARIX);Cost-saving (ROTAVAC);Cost-saving (ROTASIIL)
Total country cost of vaccination program with Gavi subsidy
$43.6 M (ROTARIX);$29.5 M (ROTAVAC); $28.0 M (ROTASIIL)
$72.6 M (ROTARIX);$65.3 M (ROTAVAC); $62.0 M (ROTASIIL)
$10.2 M (ROTARIX);$7.3 M (ROTAVAC); $6.4 M (ROTASIIL)
Least costly and most cost-effective product
ROTASIIL
ROTASIIL
ROTASIIL
There are two important findings from Scenario 1. First, ROTAVAC is now projected
to be cost-saving in two of the three countries examined. This means the cost of averted
illnesses exceeds the cost of the vaccination program, so the vaccination program
both enhances health and saves money. Second, ROTAVAC is the least costly and most
cost-effective product in all countries in this scenario, a result distinct from the
previously published analysis. Scenario 2, however, shows ROTASIIL to also be cost-saving
in two of three countries and suggests ROTASIIL is the least costly and most cost-effective
product in all three countries. In short, the economically preferred vaccine product
is sensitive and subject to change across relatively similar scenarios.
One might conclude from this revised analysis that economic information does not enhance
rotavirus vaccine product decisions because the economically preferred product is
so sensitive small changes in key inputs. That interpretation, however, overlooks
the utility of using economic evaluation to identify these sensitive parameters and
millions of dollars that a country might save through the selection of an economically
preferred product. We argue that economic considerations remain critical to product
choice but require better data on delivery costs and careful consideration of key
tradeoffs, especially the interaction of vaccine price, incremental delivery costs,
and the number of doses per course. It is likely that the least costly product in
one country may be the most expensive for a neighboring country, but we might also
see one product favored by groups of countries. For example, countries ineligible
for Gavi support might favor one product over others and we may see different trends
in the Gavi market.
This commentary avoids specific guidance to countries seeking to select an economically
preferred product but offers a few thoughts. First, economic considerations should
continue to be part of a product selection criteria and can help identify critical
uncertainties that influence results. As this discussion demonstrates, these choices
are not simple, but international partners can help provide impartial perspective
and experience. Second, any of the prequalified rotavirus vaccines are likely to be
cost-effective in most countries. Assuming products under consideration are affordable,
which should be assessed, any of the prequalified products are likely to be good economic
choices. However, the “best” choice may be highly sensitive to country context including
vaccine prices and delivery costs. Third, a periodic assessment of current product
availability, product characteristics, and prices can help ensure an effective, affordable,
and sustainable rotavirus vaccination program.
Declaration of Competing Interest
The authors declare that they have no known competing financial interests or personal
relationships that could have appeared to influence the work reported in this paper.