Comment

the wider field of MCED research to identify which authors and not necessarily those of the NIHR, the Department of Health and
technologies present the greatest likelihood of detecting Social Care England, or NHS England. Where authors are identified as personnel
of the International Agency for Research on Cancer or WHO, the authors
early-stage disease, noting that doing so is very challenging alone are responsible for the views expressed in this Comment and they do not
for certain cancer types.5–7 Research is also required on necessarily represent the decisions, policy, or views of the International Agency
for Research on Cancer or WHO. RL reports funding indirectly related to this work
cost-effectiveness, overdiagnosis, and incidental findings. from the Royal Marsden Cancer charity, Cancer Research UK, Innovate UK (co-
It would be logical to investigate approaches in which funded by Roche), RM Partners Cancer Alliance, the NIHR, and NHS England, and
unrelated to this topic consulting fees from Royal Marsden Private Care for
multicancer screening might be improved by integrating personal private practice and is NHS England Joint National Clinical Lead for the
parallel biomarkers, and where this can best synergise Targeted Lung Health Check Programme and NIHR Clinical Research Network
National Specialty Lead for Screening, Prevention and Early Detection.
with existing screening programmes, and possibly more HAR reports funding unrelated to this work from the US National Cancer
Institute, the Institut National du Cancer (France), World Cancer Research Fund
extensively validated tumour-specific biomarkers such International, and the Lung Cancer Research Foundation.
as faecal immunochemical tests and human papilloma
*Richard Lee, Hilary A Robbins
virus testing. Ultimately, MCED screening efficacy must be [email protected]
based on reduced mortality or another similar stringent Early Diagnosis and Detection Centre, the National Institute for Health and Care
demonstration of benefit against the potential harms. Research Biomedical Research Centre at the Royal Marsden and Institute of
Another wave of MCED studies is already in progress, Cancer Research, London SW3 6JJ, UK (RL); Genomic Epidemiology Branch,
International Agency for Research on Cancer, Lyon, France (HAR)
including PATHFINDER2 (NCT05155605) and NHS- 1 Nicholson BD, Oke J, Virdee PS, et al. Multi-cancer early detection test in
GALLERI,2 but these studies will not fully address these symptomatic patients referred for cancer investigation in England and
Wales (SYMPLIFY): a large-scale, observational cohort study. Lancet Oncol
questions, and non-industry-sponsored research is scarce 2023; 24: 733–43.
thus far. 2 Neal RD, Johnson P, Clarke CA, et al. Cell-free DNA-based multi-cancer early
detection test in an asymptomatic screening population (NHS-Galleri):
The exciting data in these studies should not outshine design of a pragmatic, prospective randomised controlled trial. Cancers
2022; 14: 4818.
more sobering concerns such as low sensitivity, overlap 3 Schrag D, Beer TM, McDonnell CH 3rd, et al. Blood-based tests for
with existing, proven approaches, and unknown multicancer early detection (PATHFINDER): a prospective cohort study.
Lancet 2023; 402: 1251–60.
mortality benefit and cost-effectiveness. In the wider 4 Lennon AM, Buchanan AH, Kinde I, et al. Feasibility of blood testing
MCED setting, we must consider confidence in cancer combined with PET-CT to screen for cancer and guide intervention. Science
2020; 369: eabb9601.
detection versus exclusion, test convenience, testing 5 Chen X, Gole J, Gore A, et al. Non-invasive early detection of cancer four
years before conventional diagnosis using a blood test. Nat Commun 2020;
frequency, and added value beyond existing screening 11: 3475.
approaches as well as primary cancer prevention. Above 6 Cohen JD, Li L, Wang Y, et al. Detection and localization of surgically resectable
commercial factors, public-informed and patient- 7 cancers with a multi-analyte blood test. Science 2018; 359: 926–30.
Klein EA, Richards D, Cohn A, et al. Clinical validation of a targeted
informed design should therefore determine the course methylation-based multi-cancer early detection test using an independent
validation set. Ann Oncol 2021; 32: 1167–77.
for such innovations and future research. 8
8 Gray-Burrows KA, Willis TA, Foy R, et al. Role of patient and public
This Comment represents independent research supported by the National involvement in implementation research: a consensus study. BMJ Qual Saf
Institute for Health and Care Research (NIHR) Biomedical Research Centre at 2018; 27: 858–64.
The Royal Marsden National Health Service (NHS) Foundation Trust and the
Institute of Cancer Research, London, UK. The views expressed are those of the

New estimates of preterm birth: data gaps and quality

issues linger
Preterm birth is a major public health problem affecting disabilities, including learning disabilities, behavioural See Articles page 1261

13·4 million births worldwide in 2020 according to new disorders, and visual and hearing impairment.3 The
estimates in The Lancet, with the majority of these births true global burden of preterm birth is unknown due to
occurring in southern Asia and sub-Saharan Africa.1 a shortage of data in many countries, especially in low-
Complications of preterm birth were responsible for an income and middle-income countries (LMICs). This
estimated 1 million child deaths in 2019 and were the situation is as a result of inadequate record keeping,
leading cause of death among children younger than poor measurement of gestational age, and the absence
5 years.2 Many survivors of preterm birth face lifetime of systems in countries for routinely collecting and

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 Comment

reporting preterm birth data. The proportion of home produce a final data quality category based on several
births in LMICs has been estimated at 28% with some indicators and is a strength of the study. A Bayesian
countries in sub-Saharan Africa recording rates of hierarchical regression model was used, which adjusted
greater than 50%,4 and this also adds to the data quality for bias due to differences in data sources and quality, as
staticnak1983/Getty Images

issues. well as accounting for uncertainty in the observed data,

In 2010, Blencowe and collegues5 provided the first and is another strength of the study. However, the study
national systematic estimates of preterm birth rates has some limitations. First is the failure to control for the
and trends for the period 1990–2010 in countries where potential confounding effect of the COVID-19 pandemic
For more on Born Too Soon see sufficient data were available, as part of the Born Too on the 2020 estimates, and the proportion of the
https://www.who.int/
publications/i/
Soon report. In 2014, WHO provided global, regional, population using solid fuels. A study found preterm birth
item/9789240073890 and national estimates of preterm birth, and estimates rates to be affected by the COVID-19 pandemic.7 Also, in
of changes over time for selected countries as part of southern Asia and sub-Saharan Africa, where the majority
their commitment to addressing preterm birth within of preterm births occurs, use of solid fuels is widespread8,9
the framework of the Global Strategy for Women’s, with solid fuel use causally associated with preterm birth
Children’s and Adolescents’ Health and the Every and other adverse birth outcomes.10 Controlling for the
Newborn Action Plan.6 With the availability of new data, influence of these two factors in the model was therefore
in The Lancet, Eric O Ohuma and colleagues1 have updated necessary and their effect should be assessed in the next
the preterm birth rates, and provided trend estimates iteration. Second, the estimates produced are probably
for the period 2010–20. They also provided estimates an underestimation owing to the denominator including
according to gestational age subgroups, which is novel. only livebirths and excluding stillbirths.11 Most stillbirths
The data sources for the study were administrative data are likely to be preterm and should be accounted for in
(ie, Ministry of Health and National Statistical Office the denominator. However, the current definition of
datasets in countries and areas where the coverage of preterm birth per 100 livebirths would require a change
facility births were 80% or more) and published studies of definition if subsequent iterations are to account
in countries and areas where facility births were less for stillbirth in the denominator. This fact is something
than 80%. The published studies included were published worth considering by the bodies responsible.
between 2010 and 2020, the period of the Lancet study. The findings of Ohuma and colleagues’ study will have
Ohuma and colleagues’ study estimated the number of wide global health implications by helping to assess
children born preterm globally in 2020 to be 13·4 million progress and effectiveness of interventions used to
(95% credible interval [CrI] 12·3–15·2 million) and address preterm birth during the past decade, as well
represented 9·9% (9·1–11·2) of all livebirths. The study as inform future work and interventions targeted at
showed very little progress in the reduction of preterm reducing the burden of preterm births. These findings
birth in the past decade. The 2020 estimate was will also inform programmatic investments, decisions,
slightly lower than the 2010 estimate of 13·8 million and efforts in countries and regions designed to address
(95% CrI 12·7–15·5 million) with the global annual rate the burden of preterm birth and achieve the Sustainable
of reduction from 2010 to 2020 estimated to be –0·14%. Development Goal Target 3·2 (Ending Preventable Deaths
Southern Asia and sub-Saharan Africa accounted for of Newborns and Children Under 5 Years of Age in All
approximately 65% (8 692 000 of 13 376 200) of all Countries by 2030). Ascertaining the burden of preterm
preterm births globally in 2020. Of the 33 countries and birth and understanding the disparities in national
areas categorised as having the highest data quality, and regional estimates is essential for the allocation of
none was from these two regions. The estimates for resources for prevention and care of preterm babies.
these regions were also uncertain as evident in the wider Bridging the preterm birth data gap and addressing
credible intervals. It is therefore important to focus efforts the data quality issues in southern Asia and sub-Saharan
on improving the quantity and quality of data from these Africa is very important for generating reliable estimates.
regions. This accomplishment will require counting every baby
The study accounted for data quality by developing everywhere, whether livebirth or stillbirth, and measuring
data quality categories through an iterative process to their gestational age,1 and can be achieved by improving

1216 www.thelancet.com Vol 402 October 7, 2023

 Comment

access to health services, strengthening health reporting 5 Blencowe H, Cousens S, Oestergaard MZ, et al. National, regional, and
worldwide estimates of preterm birth rates in the year 2010 with time
systems including stopping manual record keeping of trends since 1990 for selected countries: a systematic analysis and
health data, improving measurement of gestational age, implications. Lancet 2012; 379: 2162–72.
6 Chawanpaiboon S, Vogel JP, Moller AB, et al. Global, regional, and national
and establishing population registers in countries. estimates of levels of preterm birth in 2014: a systematic review and
I declare no competing interests. modelling analysis. Lancet Glob Health 2019; 7: e37–46.
7 Calvert C, Brockway MM, Zoega H, et al. Changes in preterm birth and
A Kofi Amegah stillbirth during COVID-19 lockdowns in 26 countries. Nat Hum Behav 2023;
[email protected] 7: 529–44.
8 Bonjour S, Adair-Rohani H, Wolf J, et al. Solid fuel use for household
Public Health Research Group, Department of Biomedical Sciences, University of cooking: country and regional estimates for 1980–2010.
Cape Coast, Cape Coast, Central Region, Ghana Environ Health Perspect 2013; 121: 784–90.
1 Ohuma EO, Moller A-B, Bradley E, et al. National, regional, and global 9 Amegah AK, Jaakkola JJ. Household air pollution and the sustainable
estimates of preterm birth in 2020, with trends from 2010: a systematic development goals. Bull World Health Organ 2016; 94: 215–21.
analysis. Lancet 2023; 402: 1261–71. 10 Amegah AK, Quansah R, Jaakkola JJ. Household air pollution from solid fuel
2 Perin J, Mulick A, Yeung D, et al. Global, regional, and national causes of use and risk of adverse pregnancy outcomes: a systematic review and
under-5 mortality in 2000–19: an updated systematic analysis with meta-analysis of the empirical evidence. PLoS One 2014; 9: e113920.
implications for the Sustainable Development Goals. 11 Morisaki N, Ganchimeg T, Vogel JP, et al. Impact of stillbirths on
Lancet Child Adolesc Health 2022; 6: 106–15. international comparisons of preterm birth rates: a secondary analysis of
3 WHO. Preterm birth. 2022. https://www.who.int/news-room/fact-sheets/ the WHO multi-country survey of Maternal and Newborn Health. BJOG
detail/preterm-birth (accessed May 1, 2023). 2017; 124: 1346–54.
4 Hernández-Vásquez A, Chacón-Torrico H, Bendezu-Quispe G. Prevalence
of home birth among 880,345 women in 67 low- and middle-income
countries: a meta-analysis of Demographic and Health Surveys.
SSM Popul Health 2021; 16: 100955.

Treating metastatic pancreatic ductal adenocarcinoma:

NALIRIFOX as new standard?
Pancreatic ductal adenocarcinoma, with an annual endpoint, overall survival, was 11·1 months (95% CI
number of deaths exceeding 530 000 patients,1 10·0–12·1) with NALIRIFOX group versus 9·2 months
undoubtedly requires new, potent treatment strategies. (8·3–10·6) in the nab-paclitaxel and gemcitabine group
The Surveillance, Epidemiology, and End Results (HR 0·83 [95% CI 0·70–0·99]; p=0·036). The 12 month
(SEER) programme demonstrated that in the period overall survival rate was 45·6% in the NALIRIFOX group
from 1977 to 2013, pancreatic ductal adenocarcinoma versus 39·5% in the nab-paclitaxel and gemcitabine
remained the cancer with the worst 5-year overall group. The incidence of treatment-related treatment

andresr/Getty Images
survival rate among all common cancers. In this 36-year emergent adverse events leading to death (2% in both
period, the 5-year overall survival only improved from groups) and treatment discontinuation (25% with
2·5% to 8·7%, clearly less than for most other cancers.2 NALIRIFOX vs 23% with nab-paclitaxel and gemcitabine)
In The Lancet, Zev Wainberg and colleagues present the was similar. Rates of diarrhoea (20% with NALIRIFOX vs Published Online
September 11, 2023
results of the NAPOLI-3 trial, which randomly allocated 5% with nab-paclitaxel and gemcitabine) and vomiting https://doi.org/10.1016/
770 patients with treatment-naive metastatic pancreatic (7% vs 2%) were higher with NALIRIFOX than with S0140-6736(23)01521-0

ductal adenocarcinoma (mPDAC) to NALIRIFOX nab-paclitaxel and gemcitabine, whereas neutropenia See Articles page 1272

(iposomal irinotecan 50 mg/m², oxaliplatin 60 mg/m², (24% vs 38%) was lower. Data on quality of life and
leucovorin 400 mg/m², and fluorouracil 2400 mg/m², treatment costs were not presented. The authors state,
administered sequentially as a continuous intravenous “Our findings support use of the NALIRIFOX regimen as
infusion over 46 h) on days 1 and 15 of a 28-day a possible reference regimen for first-line treatment of
cycle or nab-paclitaxel 125 mg/m² and gemcitabine mPDAC”.
1000 mg/m².3 NAPOLI-3 included patients—mean NAPOLI-3 is clearly a pivotal trial as it presents the
age 63·4 years (SD 9·1), 336 (43·6%) women, and first major development for patients with mPDAC in
639 (83·0%) White—in 187 hospitals in 18 countries more than a decade. In 2011, Conroy and colleagues
including the USA, Canada, Brazil, 12 European published a trial which randomly assigned 342 patients
countries, Israel, South Korea, and Australia. The primary with treatment-naive mPDAC between FOLFIRINOX

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