Immunisation Horizon Scanning Volume 6 Issue 5

Non-publication and delayed publication of randomized trials on vaccines: survey

Source: British Medical Journal, 2014; 348

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Date of publication: May 2014

Publication Type:  Journal Article

In a nutshell: Objective: To evaluate the extent of non-publication or delayed publication of registered randomized trials on vaccines, and to investigate potential determinants of delay to publication.

Design: Survey.

Data sources: Trials registry websites, Scopus, PubMed, Google.

Study selection: Randomized controlled trials evaluating the safety or the efficacy or immunogenicity of human papillomavirus (HPV), pandemic A/H1N1 2009 influenza, and meningococcal, pneumococcal, and rotavirus vaccines that were registered in ClinicalTrials.gov, Current Controlled Trials, WHO International Clinical Trials Registry Platform, Clinical Study Register, or Indian, Australian-New Zealand, and Chinese trial registries in 2006-12. Electronic databases were searched up to February 2014 to identify published manuscripts containing trial results. These were reviewed and classified as positive, mixed, or negative. We also reviewed the results available in ClinicalTrials.gov.

Main outcome measures: Publication status of trial results and time from completion to publication in peer reviewed journals.

Data synthesis: Cox proportional hazards regression was used to evaluate potential predictors of publication delay.

Results: We analysed 384 trials (85% sponsored by industry). Of 355 trials (404 758 participants) that were completed, 176 (n=151 379) had been published in peer reviewed journals. Another 42 trials (total sample 62 765) remained unpublished but reported results in ClinicalTrials.gov. The proportion of trials published 12, 24, 36, and 48 months after completion was 12%, 29%, 53%, and 73%, respectively. Including results posted in ClinicalTrials.gov, 48 months after study completion results were available for 82% of the trials and 90% of the participants. Delay to publication between non-industry and industry sponsored trials did not differ, but non-industry sponsored trials were 4.42-fold (P=0.008) more likely to report negative or mixed findings. Negative results were reported by only 2% of the published trials.

Conclusions: Most vaccine trials are published eventually or the results posted in ClinicalTrials.gov, but delays to publication of several years are common. Actions should focus on the timely dissemination of data from vaccine trials to the public.

Length of publication: 11-page article.

Delayed publication of vaccine trials

Source: British Medical Journal, 2014; 348

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Date of publication: May 2014

Publication Type: Editorial

In a nutshell: Among medical interventions to improve human health, vaccination has been and remains one of the most important.1 Given the huge number of deaths from influenza pandemics in recent history, the ability to rapidly develop effective vaccines for new strains of influenza is particularly critical. Making and testing a new influenza vaccine that can be administered to the public takes six months or less.2 For example, the pandemic A/H1N1 2009 influenza strain was first identified in April of 2009; four vaccines were approved by the US Food and Drug Administration in September. After the approval of a vaccine, however, important questions remain regarding dosage, effectiveness, and safety. These questions are best answered by randomized clinical trials, and getting complete results from these trials to policy makers, clinicians, and the general public in a timely manner is essential.

The problems of delayed publication and non-publication of clinical trials have been described in a variety of settings.3 4 5 In this issue of The BMJ, Manzoli and colleagues (doi:10.1136/bmj.g3058) examine delays to publication and non-publication for the vitally important area of vaccine trials.6 The authors searched …

Length of publication: 2-page article.

Measles cases in the US reach 20-year high

Source: BBC News

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Date of publication: May 2014

Publication Type: News Item

In a nutshell: Public health experts in the US are urging people to get vaccinated after a spike in measles cases in the country this year.

Length of publication:  1-page article.

Evaluation of safety of A/H1N1 pandemic vaccination during pregnancy: cohort study

Source: British Medical Journal, 2014; 348

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Date of publication: May 2014

Publication Type: Journal Article

In a nutshell:  Objective To assess the risk of maternal, fetal, and neonatal outcomes associated with the administration of an MF59 adjuvanted A/H1N1 vaccine during pregnancy.

Design Historical cohort study.

Setting Singleton pregnancies of the resident population of the Lombardy region of Italy.

Participants All deliveries between 1 October 2009 and 30 September 2010. Data on exposure to A/H1N1 pandemic vaccine, pregnancy, and birth outcomes were retrieved from regional databases. Vaccinated and non-vaccinated women were compared in a propensity score matched analysis to estimate risks of adverse outcomes.

Main outcome measures Main maternal outcomes included type of delivery, admission to intensive care unit, eclampsia, and gestational diabetes; fetal and neonatal outcomes included perinatal deaths, small for gestational age births, and congenital malformations.

Results Among the 86 171 eligible pregnancies, 6246 women were vaccinated (3615 (57.9%) in the third trimester and 2557 (40.9%) in the second trimester). No difference was observed in terms of spontaneous deliveries (adjusted odds ratio 1.02, 95% confidence interval 0.96 to 1.08) or admissions to intensive care units (0.95, 0.47 to 1.88), whereas a limited increase in the prevalence of gestational diabetes (1.26, 1.04 to 1.53) and eclampsia (1.19, 1.04 to 1.39) was seen in vaccinated women. Rates of fetal and neonatal outcomes were similar in vaccinated and non-vaccinated women. A slight increase in congenital malformations, although not statistically significant, was present in the exposed cohort (1.14, 0.99 to 1.31).

Conclusions Our findings add relevant information about the safety of the MF59 adjuvanted A/H1N1 vaccine in pregnancy. Residual confounding may partly explain the increased risk of some maternal outcomes. Meta-analysis of published studies should be conducted to further clarify the risk of infrequent outcomes, such as specific congenital malformations.

Length of publication: 11-page article.

H1N1 influenza vaccination during pregnancy

Source: British Medical Journal, 2014; 348

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Date of publication: May 2014

Publication Type: Editorial

In a nutshell: H1N1 safety data look reassuring, but we need ongoing surveillance of all influenza vaccines given to pregnant women

Risks to pregnant women from influenza infection have long been recognized.1 The recent 2009-10 H1N1 pandemic was no exception—pregnant women were at higher risk of severe H1N1 influenza illness compared with the general population,2 and those with H1N1 influenza had higher rates of adverse pregnancy outcomes than did uninfected pregnant women.3 Despite limited safety data for use of the monovalent H1N1 vaccines in pregnancy, pregnant women were widely prioritized for H1N1 vaccination programs.4 Fortunately, enhanced surveillance of pregnant women during the pandemic has enabled retrospective evaluation of the safety of monovalent H1N1 vaccine in obstetric populations around the world.

One such evaluation is published in this issue of The BMJ (doi:10.1136/bmj.g3361). Trotta and colleagues report findings from their large retrospective cohort study assessing the relation between an adjuvanted monovalent pandemic H1N1 vaccine administered during pregnancy and adverse maternal and fetal/neonatal outcomes.5 The study was conducted in the Lombardy region of northern Italy and examined a population of 86 171 women with a singleton pregnancy ending in a live birth or stillbirth between 1 October 2009 and 30 September …

Length of publication: 2-page article.

Systematic review of human papillomavirus vaccine coadministration

Source: Vaccine, 2014; 32(23); 2670–2674

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Date of publication: April 2014

Publication Type:  Review

Human papillomavirus (HPV) vaccination is recommended in early adolescence, at an age when other vaccines are also recommended. Administration of multiple vaccines during one visit is an opportunity to improve uptake of adolescent vaccines. We conducted a systematic review of safety and immunogenicity of HPV vaccines coadministered with other vaccines. Our review included 9 studies, 4 of quadrivalent HPV vaccine and 5 of bivalent HPV vaccine; coadministered vaccines included: meningococcal conjugate, hepatitis A, hepatitis B, combined hepatitis A and B, tetanus, diphtheria, acellular pertussis, and inactivated poliovirus vaccines. Studies varied in methods of data collection and measurement of immunogenicity and safety. Noninferiority of immune response and an acceptable safety profile were demonstrated when HPV vaccine was coadministered with other vaccines.

Length of publication: 5-page article.

Cluster randomized trial of a toolkit and early vaccine delivery to improve childhood influenza vaccination rates in primary care

Source: Vaccine, 2014; pii: S0264-410X(14)00595-7

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Date of publication: April 2014

Publication Type: Journal Article

In a nutshell: Purpose: To increase childhood influenza vaccination rates using a toolkit and early vaccine delivery in a randomized cluster trial.

Methods: Twenty primary care practices treating children (range for n = 536–8183) were randomly assigned to Intervention and Control arms to test the effectiveness of an evidence-based practice improvement toolkit (4 Pillars Toolkit) and early vaccine supplies for use among disadvantaged children on influenza vaccination rates among children 6 months–18 years. Follow-up staff meetings and surveys were used to assess use and acceptability of the intervention strategies in the Intervention arm. Rates for the 2010–2011 and 2011–2012 influenza seasons were compared. Two-level generalized linear mixed modeling was used to evaluate outcomes.

Results: Overall increases in influenza vaccination rates were significantly greater in the Intervention arm (7.9 percentage points) compared with the Control arm (4.4 percentage points; P < 0.034). These rate changes represent 4522 additional doses in the Intervention arm vs. 1390 additional doses in the Control arm. This effect of the intervention was observed despite the fact that rates increased significantly in both arms – 8/10 Intervention (all P < 0.001) and 7/10 Control sites (P-values = 0.04 to <0.001). Rates in two Intervention sites with pre-intervention vaccination rates >58% did not significantly increase. In regression analyses, a child’s likelihood of being vaccinated was significantly higher with: younger age, white race (Odds ratio [OR] = 1.29; 95% confidence interval [CI] = 1.23–1.34), having commercial insurance (OR = 1.30; 95%CI = 1.25–1.35), higher pre-intervention practice vaccination rate (OR = 1.25; 95%CI = 1.16–1.34), and being in the Intervention arm (OR = 1.23; 95%CI = 1.01–1.50). Early delivery of influenza vaccine was rated by Intervention practices as an effective strategy for raising rates.

Conclusions: Implementation of a multi-strategy toolkit and early vaccine supplies can significantly improve influenza vaccination rates among children in primary care practices but the effect may be less pronounced in practices with moderate to high existing vaccination rates.

Length of publication:

Influenza vaccine in pregnancy: policy and research strategies

Source: The Lancet, 2014; 383(9929); 60583-3

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Date of publication: May 2014

Publication Type: Comment

In a nutshell: Influenza vaccination in pregnancy reduces maternal illness, improves fetal outcomes, prevents influenza in the infant up to 6 months of age, and potentially improves long-term adult outcomes for the infant ( table 1 ). These effects on four life stages are not widely known by policy makers, and we provide a summary with recommendations for policy and needed research.

Length of publication: 3-page article.

Faster vaccination response is needed to curb effects of flu pandemics, study concludes

Source: British Medical Journal, 2014; 348

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Date of publication: May 2014

Publication Type: News Item

In a nutshell: To substantially reduce illness, deaths, and costs from severe flu pandemics, vaccination campaigns need to be launched much sooner than they were in the United States during the H1N1 “swine flu” pandemic in 2009, a new computer modeling study indicates.

The study appears in the current issue of Annals of Internal Medicine.1 Nayer Khazeni of the Division of Pulmonary and Critical Care Medicine, Stanford University Medical Center in Stanford, California, was the study’s lead author.

Large scale vaccination against H1N1 influenza A in 2009 did not occur in the US until nine months after the beginning of the pandemic, by which time two waves of infections had already passed through the population. Fortunately, the virus proved to be far less virulent than was initially thought, and the death rate …

Length of publication: 1-page article.