Archivos argentinos de pediatria.
JP Morgans DR Advisor Series
Two were cohort studies 30 , 33 , while the other three were geographical association studies 29 , 31 , No estimates relative risks of vaccination efficacy could be obtained from any of the observational studies, so ultimately these studies could not be included in the analysis and evaluation of evidence. Instead, they were taken only as supporting evidence for the efficacy of vaccination in terms of specific outcomes details available from the authors.
One further observational study was published after the search of the literature had been completed. This analyzed data from the Australian vaccination program for the state of Victoria As the trial by De Carvalho et al. Overall, evidence quality for long-term follow-up was therefore low to very low details available from the authors. This systematic review shows that there is no evidence from long-term follow-up that vaccine protection following vaccination for HPV types 16 and 18 decreases.
Data on long-term follow-up was taken from only one study 20 , which had a considerably smaller number of participants; this explains why the effect was insignificant and the confidence interval very wide. Because only a few RCTs were conducted for five years or longer and these had considerably fewer participants than studies with shorter follow-up, the quality of evidence for long-term protection is lower than that for short-term protection.
However, the premise of stable long-term protection is supported by data that shows induction of a robust immune memory following HPV booster vaccination Our work focused on study participants in whom incident HPV infection with the types of HPV contained in the vaccine was ruled out when they were enrolled in the studies. The highest vaccination efficacy was achieved when girls and young women were vaccinated before their first possible HPV infection.
The main route of transmission of HPV infections of the cervix is sexual contact, and the probability of HPV infection rises substantially when an individual becomes sexually active HPV vaccination should therefore be completed before the beginning of sexual activity. The observational studies we identified provided no information that went beyond the data obtained from the RCTs.
This was partly because all the existing observational studies yielded data only on short-term follow-up, for which there is already relatively good evidence from RCTs. It was also partly because the designs of some observational studies were not suitable for generating data on vaccination efficacy, and others did not provide any data on girls or young women without HPV infection, which was the group focused on here.
Nevertheless, these studies are an additional source of evidence showing an effect of HPV vaccination on various outcomes following widespread use in the target group. This systematic review focuses on studies investigating efficacy of vaccination in short- and long-term follow-up; data on adverse drug reactions ADRs was not included in the evaluation according to the study protocol.
Two recent systematic reviews have analyzed data on ADRs following HPV vaccination; both concluded that the studies included did not show any significant differences between vaccinated and non-vaccinated participants in terms of relevant outcomes, and that the safety profile of vaccination was acceptable 12 , A recently published systematic review also demonstrates the efficacy and safety of HPV vaccination when coadministered with other vaccines The limitations of this article concern the focus on girls and women with no HPV infection.
The results are extrapolated to the actual target group for vaccination, girls and young women who are not yet sexually active. It must also be assumed that the data for other target groups such as older women or young men is different in terms of both efficacy data and evidence quality. The particular strength of this article is that this is the first time a comprehensive systematic review has provided a conclusion on the long-term efficacy of HPV vaccine protection for the most important vaccination target group on the basis of meta-analysis.
In addition, the standardized, international GRADE guidelines have been used to provide a conclusion on the quality of the evidence, differentiated by length of follow-up. This supports a critical assessment of this data. The following data was extracted: The GRADE guidelines 18 provide a transparent system for assessing evidence and developing recommendations.
According to GRADE, evidence quality is a measure of confidence in the correctness of estimates of effect sizes: The units of analysis used by GRADE are outcomes; in other words, evidence quality concerns a single outcome. When the body of evidence, i. Evidence quality can then be up- or downgraded on the basis of an established set of criteria covering aspects of both internal and external validity. Quality can be downgraded according to five criteria: GRADE assessment of evidence is separate from the stage at which the evidence is used as the basis for a recommendation.
Where there was heterogeneity revealed by a statistically significant chi-square test or I 2 statistics , a random-effects model was used. In other cases, data was pooled using a fixed-effects model.
Due to the limited number of studies per outcome no test for publication bias was performed, in line with the recommendations of the Cochrane Collaboration. All evaluations were performed for a follow-up duration of less than five years short-term follow-up and five years or more long-term follow-up. Conflict of interest statement.
Zepp has received reimbursement of conference fees, travel expenses, and accommodation expenses from GSK. He has received fees for conducting commissioned clinical studies from GSK and Sanofi. Harder, PD Wichmann, Dr. Klug declare that no conflict of interest exists.
Terhardt has received fees for continuing education lectures unrelated to any specific product, for which financial recompense was provided by vaccine manufacturers AstraZeneca, Sanofi. National Center for Biotechnology Information , U. Journal List Dtsch Arztebl Int v. Published online Sep 1. Author information Article notes Copyright and License information Disclaimer.
Received May 15; Accepted Jun See letter " Correspondence letter to the editor: See letter " Correspondence reply: This article has been cited by other articles in PMC. Method Systematic literature review and meta-analysis on the efficacy of vaccination, with assessment of evidence by the GRADE criteria Grading of Recommendations Assessment, Development and Evaluation. Results 15 studies were identified: Conclusion Long-term observation does not indicate any loss of antiviral protection after vaccination against HPV 16 and 18, although the evidence for long-term protection is of lesser quality than that for short-term protection.
Methods A systematic review was performed to address the following primary questions: What is the quality according to the GRADE guidelines of the evidence on the efficacy of vaccination in long-term follow-up in comparison to evidence obtained during short-term follow-up?
Study selection The study inclusion criteria were set using the PICO population, intervention, control, outcome question established before the beginning of the study and stated in the study protocol Table.
Population Girls or women aged 9 to Vaccination according to the schedule 0—1 —2 —6 months or similar , with no booster vaccination after the end of initial immunization. Open in a separate window. Results The search strategy shown in eBox 1 identified potentially relevant publications. Study characteristics The RCTs involved a total of 46 participants 23 individuals vaccinated against HPV, 23 control participants. The studies yielded the following short-term follow-up data: Study findings RCTs—short-term follow-up: Conclusion This systematic review shows that there is no evidence from long-term follow-up that vaccine protection following vaccination for HPV types 16 and 18 decreases.
Persistent infection with a high-risk human papillomavirus HPV type is a necessary prerequisite for the development of dysplasia and neoplasia of the cervix. Since , the German Standing Committee on Vaccination STIKO has recommended that girls aged between 12 and 17 receive vaccination against the high-risk types 16 and 18 of the human papillomavirus. For the first time, a systematic review has been performed using pooled estimates of the duration of vaccine protection.
This meta-analysis shows that the long-term five years or longer follow-up data published to date contains no evidence of a drop in vaccine protection following vaccination against HPV types 16 and RCTs investigating the duration of protection of HPV vaccination should be continued in order to improve the quality of evidence on long-term protection.
Observational studies estimating the efficacy of vaccination in terms of various outcomes should be initiated to support the evidence. Footnotes Conflict of interest statement Prof. Human papillomavirus and cervical cancer. Human Papillomavirus prevalence and probable first effects of vaccination in 20 to 25 year-old women in Germany: Natural history of cervical neoplasia and risk of invasive cancer in women with cervical intraepithelial neoplasia 3: Wie wirksam ist die HPV-Impfung?
A review of clinical trials of human papillomavirus prophylactic vaccines. Comprehensive control of human papillomavirus infections and related diseases. National Advisory Groups and their role in immunization policy-making processes in European countries. Clinical microbiology and infection. Prophylactic vaccination against human papillomavirus infection and disease in women: Efficacy of human papillomavirus vaccines: International journal of gynecological cancer: Efficacy and safety of prophylactic vaccines against cervical HPV infection and diseases among women: Efficacy and safety of human papilloma virus vaccine in cervical cancer prevention: Archivos argentinos de pediatria.
Cross-protective efficacy of two human papillomavirus vaccines: Foreign companies that want their stock to be limited to being traded by only certain individuals may set up a restricted program.
Rule A and Regulation S. This provision makes the issuance of shares a private placement. Shares of companies registered under Rule A are restricted stock and may only be issued to or traded by qualified institutional buyers QIBs. The other way to restrict the trading of depositary shares to U. This regulation means that the shares are not, and will not be registered with any U.
The shares are registered and issued to offshore, non-U. One can either source new ADRs by depositing the corresponding domestic shares of the company with the depositary bank that administers the ADR program or, instead, one can obtain existing ADRs in the secondary market. The latter can be achieved either by purchasing the ADRs on a U. Most ADR programs are subject to possible termination. Termination of the ADR agreement will result in cancellation of all the depositary receipts, and a subsequent delisting from all exchanges where they trade.
The termination can be at the discretion of the foreign issuer or the depositary bank, but is typically at the request of the issuer. There may be a number of reasons why ADRs terminate, but in most cases the foreign issuer is undergoing some type of reorganization or merger. Owners of ADRs are typically notified in writing at least thirty days prior to a termination.
Once notified, an owner can surrender their ADRs and take delivery of the foreign securities represented by the Receipt, or do nothing. If an ADR holder elects to take possession of the underlying foreign shares, there is no guarantee the shares will trade on any U. The holder of the foreign shares would have to find a broker who has trading authority in the foreign market where those shares trade. If the owner continues to hold the ADR past the effective date of termination, the depositary bank will continue to hold the foreign deposited securities and collect dividends, but will cease distributions to ADR owners.
Usually up to one year after the effective date of the termination, the depositary bank will liquidate and allocate the proceeds to those respective clients. Many US brokerages can continue to hold foreign stock, but may lack the ability to trade it overseas. Securities Exchange Act of From Wikipedia, the free encyclopedia.
This article needs additional citations for verification. Please help improve this article by adding citations to reliable sources. Unsourced material may be challenged and removed. September Learn how and when to remove this template message. Derivatives Credit derivative Futures exchange Hybrid security. Foreign exchange Currency Exchange rate.