Milestones :: Perspectives

Milestones :: Perspectives
 
Opinion: We need more ambitious global health targets
By Seth Berkley
Devex – Focus On: Global Health
25 August 2017
If you’re going to try to make the world a better place, it’s important to think big and aim high. Combating climate change, protecting the world’s fish stocks or ending extreme poverty, hunger and gender inequality by 2030 are global goals that do precisely this. But while achievable, the ability of governments to meet these targets, and all 17 Sustainable Development Goals promised by all world leaders, is dependent not just on the goals and their targets themselves, but on how ambitiously we measure our progress toward reaching them.

For the global health targets of ending preventable deaths of under 5 and achieving universal health coverage with access to affordable and essential vaccines for all, which are all part of SDG 3, that could be a problem. In fact, we may already be in danger of setting ourselves up to fail even before we’ve barely begun. A lack of ambition in how we measure progress toward these SDG 3 targets will not only give us a false assessment of how well we’re doing, but could also hamper our chances of success, putting the lives of millions of the most vulnerable children at risk in the process.

Keeping track of how many children receive two doses of a measles-containing vaccine is currently the SDG 3 progress indicator being considered for these two targets. At first glance, this may seem like a sensible choice; an immunization indicator is a great idea because it is universal and has such a direct impact on reducing childhood mortality. Also, measles, is an important vaccine that has been saving lives for more than half a century, and is already used as a tracer vaccine to gauge how many children have access to routine immunization, so a reporting system is already in place. The problem is MCV2 alone simply doesn’t go far enough.
It’s the equivalent of assessing the health of the oceans only on acidity samples taken from around our coastlines, or measuring poverty by only counting those people living in households that already have access to basic services. If we did this, then we’d end up with a very incomplete picture. It is the same with our immunization health indicators.

While measles is a certainly a big killer, claiming more than 130,000 lives every year — mainly children — there are new vaccines that can have a potentially even bigger impact on reducing childhood mortality, vaccines such as pneumococcal conjugate vaccine and rotavirus. Yet, despite protecting against the two biggest killers of under 5, pneumonia and diarrhea, they are relatively recently introduced vaccines and so coverage is still relatively low, at 42 percent and 25 percent, respectively. Other vaccines protect against cancer, meningitis and birth defects. Our worry now is that if we base progress purely on MCV2, then we could end up in a situation where we think we are doing better than we actually are, and in doing so miss the opportunity to save more lives.

The World Health Organization currently recommends that all children are vaccinated to protect them against 11 different infectious diseases. Confining our measurement to just one of those antigens will not capture how many children are fully immunized. Today, global coverage of children receiving MCV2 stands at 64 percent, suggesting that one-third of all children are missing out. But if you instead look at how many children are receiving all of the 11 antigens, then a very different picture emerges. Based on Gavi’s best analysis just 7 percent of the children living in the 73 world’s poorest countries — those we need to be focusing on to decrease child mortality — are fully immunized. This means we have considerably further to go to meet our targets than MCV2 alone would suggest, with more than nine out of 10 children not getting the minimum protection against infectious diseases.

So why isn’t the global health community considering using the proportion of fully immunized children to track progress instead? One reason is that it’s a lot more difficult, both to measure and to achieve. Today immunization coverage data is based on how many vaccine doses are given, rather than counting the number vaccines each child has received. Given that one-in-three children don’t officially exist, because their birth was not formally registered, it’s easy to see why. And even though more children have vaccination cards than birth certificates, the systems that would be needed to monitor these generally do not exist.

But with a little help from technology they could. The technology sector is already striving to achieve global penetration, reaching everyone. So, it’s quite conceivable that we could have new and affordable digital ID systems capable of working in poorly resourced settings, even where there is no reliable electricity. By leapfrogging existing and often archaic paper-based methods used to certify births we will improve our ability to reach everyone and keep track of those that are missing out, whether they are living in remote village or urban slums. This is not just wishful thinking; SDG 16 already demands it, with everyone on this planet required to have a legal form of identity by 2030.

Ultimately, MCV2 alone will simply not cut it. We need to be more ambitious. Even choosing one of the powerful new vaccines that are making a difference in child mortality would make more of a difference. But going even further and making the child the focal point of immunization monitoring would be nothing short of revolutionary. Not only will it help radically reduce childhood mortality, but it will represent a significant step toward the WHO’s goal of achieving universal health coverage, which aims to ensure that everyone has access to affordable, quality health care — no matter who they are or where they live — and that includes ensuring every child has access to the most cost-effective health intervention and is fully immunized.

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Progress and Challenges with Achieving Universal Immunization Coverage: 2016 Estimates of Immunization Coverage
WHO/UNICEF Estimates of National Immunization Coverage (Data as of July 2017)
[Excerpts]
DTP3 coverage remains at 86% in 2016, leaving 19.5 million children vulnerable to vaccine preventable diseases.
86% of the world’s children received the required 3 doses of diphtheria-tetanus-pertussis containing vaccines (DTP3) in 2016, a coverage level that has remained stable at about 85% since 2010. As a result, 19.5 million children did not receive routine life-saving vaccinations. This falls short of global immunization targets.
In 2012, all 194 WHO Member States endorsed the Global Vaccine Action Plan (GVAP) and
committed to ensuring no one misses out on vital immunizations, with a target of achieving 90% DTP3 vaccination coverage in all countries by 2015.
Unvaccinated includes all children that didn’t complete the three-dose schedule of a diphtheria-tetanus-pertussis containing vaccine, as well those that didn’t receive any dose of the same
vaccine

1 in ten children remain unreached by immunization programmes
The recently released vaccination coverage estimates also suggest that about 1 in 10 infants worldwide do not have access to vaccination, not having received even the first DTP-containing vaccine dose (DTP1). Most of the children that remain un-immunized are the same ones missed by health systems.

To reach GVAP objectives, nearly 10 million additional infants would need to have been vaccinated in 2016
If all countries are to reach at least 90% DTP3 vaccination coverage, 9.9 million additional
children would need to be vaccinated in 64 countries. Three in four of these children live in fragile countries, including countries that are affected by conflict; 4 out of 10 live in the three countries that have yet to interrupt polio transmission, namely Nigeria, Afghanistan and Pakistan….
 
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Bulletin of the World Health Organization
Volume 95, Number 9, September 2017, 609-664
http://www.who.int/bulletin/volumes/95/9/en/
RESEARCH
Estimated economic impact of vaccinations in 73 low- and middle-income countries, 2001–2020
Sachiko Ozawa, Samantha Clark, Allison Portnoy, Simrun Grewal, Meghan L Stack, Anushua Sinha, Andrew Mirelman, Heather Franklin, Ingrid K Friberg, Yvonne Tam, Neff Walker, Andrew Clark, Matthew Ferrari, Chutima Suraratdecha, Steven Sweet, Sue J Goldie, Tini Garske, Michelle Li, Peter M Hansen, Hope L Johnson & Damian Walker
http://dx.doi.org/10.2471/BLT.16.178475
Abstract [HTML]
Objective
To estimate the economic impact likely to be achieved by efforts to vaccinate against 10 vaccine-preventable diseases between 2001 and 2020 in 73 low- and middle-income countries largely supported by Gavi, the Vaccine Alliance.
Methods
We used health impact models to estimate the economic impact of achieving forecasted coverages for vaccination against Haemophilus influenzae type b, hepatitis B, human papillomavirus, Japanese encephalitis, measles, Neisseria meningitidis serogroup A, rotavirus, rubella, Streptococcus pneumoniae and yellow fever. In comparison with no vaccination, we modelled the costs – expressed in 2010 United States dollars (US$) – of averted treatment, transportation costs, productivity losses of caregivers and productivity losses due to disability and death. We used the value-of-a-life-year method to estimate the broader economic and social value of living longer, in better health, as a result of immunization.
Findings
We estimated that, in the 73 countries, vaccinations given between 2001 and 2020 will avert over 20 million deaths and save US$ 350 billion in cost of illness. The deaths and disability prevented by vaccinations given during the two decades will result in estimated lifelong productivity gains totalling US$ 330 billion and US$ 9 billion, respectively. Over the lifetimes of the vaccinated cohorts, the same vaccinations will save an estimated US$ 5 billion in treatment costs. The broader economic and social value of these vaccinations is estimated at US$ 820 billion.
Conclusion
By preventing significant costs and potentially increasing economic productivity among some of the world’s poorest countries, the impact of immunization goes well beyond health
 
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FDA approval brings first gene therapy to the United States
CAR T-cell therapy approved to treat certain children and young adults with B-cell acute lymphoblastic leukemia
August 30, 2017   FDA News Release

The U.S. Food and Drug Administration issued a historic action today making the first gene therapy available in the United States, ushering in a new approach to the treatment of cancer and other serious and life-threatening diseases.

The FDA approved Kymriah (tisagenlecleucel) for certain pediatric and young adult patients with a form of acute lymphoblastic leukemia (ALL).

“We’re entering a new frontier in medical innovation with the ability to reprogram a patient’s own cells to attack a deadly cancer,” said FDA Commissioner Scott Gottlieb, M.D. “New technologies such as gene and cell therapies hold out the potential to transform medicine and create an inflection point in our ability to treat and even cure many intractable illnesses. At the FDA, we’re committed to helping expedite the development and review of groundbreaking treatments that have the potential to be life-saving.”

Kymriah, a cell-based gene therapy, is approved in the United States for the treatment of patients up to 25 years of age with B-cell precursor ALL that is refractory or in second or later relapse.

Kymriah is a genetically-modified autologous T-cell immunotherapy. Each dose of Kymriah is a customized treatment created using an individual patient’s own T-cells, a type of white blood cell known as a lymphocyte. The patient’s T-cells are collected and sent to a manufacturing center where they are genetically modified to include a new gene that contains a specific protein (a chimeric antigen receptor or CAR) that directs the T-cells to target and kill leukemia cells that have a specific antigen (CD19) on the surface. Once the cells are modified, they are infused back into the patient to kill the cancer cells.

ALL is a cancer of the bone marrow and blood, in which the body makes abnormal lymphocytes. The disease progresses quickly and is the most common childhood cancer in the U.S. The National Cancer Institute estimates that approximately 3,100 patients aged 20 and younger are diagnosed with ALL each year. ALL can be of either T- or B-cell origin, with B-cell the most common. Kymriah is approved for use in pediatric and young adult patients with B-cell ALL and is intended for patients whose cancer has not responded to or has returned after initial treatment, which occurs in an estimated 15-20 percent of patients.

“Kymriah is a first-of-its-kind treatment approach that fills an important unmet need for children and young adults with this serious disease,” said Peter Marks, M.D., Ph.D., director of the FDA’s Center for Biologics Evaluation and Research (CBER). “Not only does Kymriah provide these patients with a new treatment option where very limited options existed, but a treatment option that has shown promising remission and survival rates in clinical trials.”

The safety and efficacy of Kymriah were demonstrated in one multicenter clinical trial of 63 pediatric and young adult patients with relapsed or refractory B-cell precursor ALL. The overall remission rate within three months of treatment was 83 percent.

Treatment with Kymriah has the potential to cause severe side effects. It carries a boxed warning for cytokine release syndrome (CRS), which is a systemic response to the activation and proliferation of CAR T-cells causing high fever and flu-like symptoms, and for neurological events. Both CRS and neurological events can be life-threatening. Other severe side effects of Kymriah include serious infections, low blood pressure (hypotension), acute kidney injury, fever, and decreased oxygen (hypoxia). Most symptoms appear within one to 22 days following infusion of Kymriah. Since the CD19 antigen is also present on normal B-cells, and Kymriah will also destroy those normal B cells that produce antibodies, there may be an increased risk of infections for a prolonged period of time.

The FDA today also expanded the approval of Actemra (tocilizumab) to treat CAR T-cell-induced severe or life-threatening CRS in patients 2 years of age or older. In clinical trials in patients treated with CAR-T cells, 69 percent of patients had complete resolution of CRS within two weeks following one or two doses of Actemra.

Because of the risk of CRS and neurological events, Kymriah is being approved with a risk evaluation and mitigation strategy (REMS), which includes elements to assure safe use (ETASU). The FDA is requiring that hospitals and their associated clinics that dispense Kymriah be specially certified. As part of that certification, staff involved in the prescribing, dispensing, or administering of Kymriah are required to be trained to recognize and manage CRS and neurological events. Additionally, the certified health care settings are required to have protocols in place to ensure that Kymriah is only given to patients after verifying that tocilizumab is available for immediate administration. The REMS program specifies that patients be informed of the signs and symptoms of CRS and neurological toxicities following infusion – and of the importance of promptly returning to the treatment site if they develop fever or other adverse reactions after receiving treatment with Kymriah.

To further evaluate the long-term safety, Novartis is also required to conduct a post-marketing observational study involving patients treated with Kymriah.

The FDA granted Kymriah Priority Review and Breakthrough Therapy designations. The Kymriah application was reviewed using a coordinated, cross-agency approach. The clinical review was coordinated by the FDA’s Oncology Center of Excellence, while CBER conducted all other aspects of review and made the final product approval determination.

The FDA granted approval of Kymriah to Novartis Pharmaceuticals Corp. The FDA granted the expanded approval of Actemra to Genentech Inc.