scholarly journals Efficacy of the AS04-Adjuvanted HPV16/18 Vaccine: Pooled Analysis of the Costa Rica Vaccine and PATRICIA Randomized Controlled Trials

2019 ◽  
Vol 112 (8) ◽  
pp. 818-828 ◽  
Author(s):  
Joseph E Tota ◽  
Frank Struyf ◽  
Joshua N Sampson ◽  
Paula Gonzalez ◽  
Martin Ryser ◽  
...  
Keyword(s):  
Young Adults ◽  
Costa Rica ◽  
Randomized Controlled Trials ◽  
Vaccine Trial ◽  
Intraepithelial Neoplasia ◽  
Controlled Trials ◽  
High Efficacy ◽  
Randomized Controlled ◽  
Squamous Intraepithelial Neoplasia ◽  
Hpv Types

Abstract Background The AS04-adjuvanted HPV16/18 (AS04-HPV16/18) vaccine provides excellent protection against targeted human papillomavirus (HPV) types and a variable degree of cross-protection against others, including types 6/11/31/33/45. High efficacy against any cervical intraepithelial neoplasia grade 3 or greater (CIN3+; >90%) suggests that lower levels of protection may exist for a wide range of oncogenic HPV types, which is difficult to quantify in individual trials. Pooling individual-level data from two randomized controlled trials, we aimed to evaluate AS04-HPV16/18 vaccine efficacy against incident HPV infections and cervical abnormalities . Methods Data were available from the Costa Rica Vaccine Trial (NCT00128661) and Papilloma Trial Against Cancer in Young Adults trial (NCT00122681), two large-scale, double-blind randomized controlled trials of the AS04-HPV16/18 vaccine. Primary analyses focused on disease-free women with no detectable cervicovaginal HPV at baseline. Results A total of 12 550 women were included in our primary analyses (HPV arm = 6271, control arm = 6279). Incidence of 6-month persistent oncogenic and nononcogenic infections, excluding known and accepted protected types 6/11/16/18/31/33/45 (focusing on 34/35/39/40/42/43/44/51/52/53/54/56/58/59/66/68/73/70/74), was statistically significantly lower in the HPV arm than in the control arm (efficacy = 9.9%, 95% confidence interval [CI] = 1.7% to 17.4%). Statistically significant efficacy (P < .05) was observed for individual oncogenic types 16/18/31/33/45/52 and nononcogenic types 6/11/53/74. Efficacy against cervical abnormalities (all types) increased with severity, ranging from 27.7% (95% CI = 21.7% to 33.3%) to 58.7% (95% CI = 34.1% to 74.7%) for cytologic outcomes (low-grade squamous intraepithelial neoplasia lesion or greater, and high-grade squamous intraepithelial neoplasia lesion or greater, respectively) and 66.0% (95% CI = 54.4% to 74.9%) to 87.8% (95% CI = 71.1% to 95.7%) for histologic outcomes (CIN2+ and CIN3+, respectively). Comparing Costa Rica Vaccine Trial and Papilloma Trial Against Cancer in Young Adults results, there was no evidence of heterogeneity, except for type 51 (efficacy = −28.6% and 20.7%, respectively; two-sided P = .03). Conclusions The AS04-HPV16/18 vaccine provides some additional cross-protection beyond established protected types, which partially explains the high efficacy against CIN3+.

The design of randomized controlled trials of veterinary vaccines

2004 ◽  
Vol 5 (2) ◽  
pp. 235-238 ◽  
Author(s):  
Ian R. Dohoo
Keyword(s):  
Randomized Controlled Trials ◽  
Vaccine Trial ◽  
Controlled Trials ◽  
Group Level ◽  
Randomized Controlled ◽  
Vaccine Trials ◽  
Veterinary Vaccine ◽  
The Individual ◽  
Clear Statement ◽  
Group Effects

AbstractRandomized controlled trials of veterinary vaccines are essential if we are to have a reasonable understanding of how those vaccines can be expected to perform when used in the field. This manuscript reviews a few (but certainly not all) of the key elements that need to be considered in the design of veterinary vaccine trials. The first step in the design of such a trial is to have a clear statement of the objective of the trial that reflects what is expected of the vaccine (e.g. should it minimize clinical disease or does it need to prevent infection?). Because domestic animals are often managed in groups, the ‘unit of concern’ used in a vaccine trial becomes of great importance. Whether the trial should be carried out at the individual or group level will depend on the objectives of the trial and the extent of concern about ‘group effects’ affecting the trial. Sample sizes will also be influenced heavily by the choice of unit of concern and the nature of the primary outcome being assessed. Finally, while there is no easy solution (except to conduct group-level trials, which may be logistically impossible), the potential for group effects to influence the trial outcome must be considered.

Pityriasis Rosea: An Updated Review

2020 ◽  
Vol 16 ◽  
Author(s):  
Alexander K. C. Leung ◽  
Joseph M. Lam ◽  
Kin Fon Leong ◽  
Kam Lun Hon
Keyword(s):  
Young Adults ◽  
Randomized Controlled Trials ◽  
Christmas Tree ◽  
Controlled Trials ◽  
Diagnostic Challenge ◽  
Pityriasis Rosea ◽  
Active Intervention ◽  
Randomized Controlled ◽  
Clinical Variants ◽  
Children And Young Adults

Background: Pityriasis rosea is a common acute, self-limited papulosquamous dermatosis that primarily affects children and young adults. The condition and its clinical variants may pose a diagnostic challenge, especially in the absence of the herald patch. Objective: This article aimed to familiarize pediatricians with clinical manifestations, evaluation, diagnosis, and management of pityriasis rosea. Methods: A search was conducted in March 2020 in Pubmed Clinical Queries using the key term " pityriasis rosea". The search strategy included all clinical trials (including open trials, non-randomized controlled trials, and randomized controlled trials), observational studies, and reviews (including narrative reviews and meta-analyses) published within the past 10 years. Only papers published in the English literature were included in this review. The information retrieved from the above search was used in the compilation of the present article. Results: Pityriasis rosea occurs mainly in individuals between 10 and 35 years of age with a peak during adolescence. Human herpesvirus (HHV)-7 and HHV-6 have been implicated as the causative agents in some patients with pityriasis rosea. A mild prodrome consisting of headaches, fever, malaise, fatigue, anorexia, sore throat, enlarged lymph nodes and arthralgia is present in about 5% of patients. The most common presenting sign, found in approximately 80% of patients, is a "herald" or “mother” patch which is larger and more noticeable than the lesions of the later eruption. A generalized, bilateral, symmetrical eruption develops in approximately 4 to 14 days and continues to erupt in crops over the next 12 to 21 days. Typical lesions are 0.5 to 1 cm, oval or elliptical, dull pink or salmon-colored macules with a delicate collarette of scales at the periphery. The long axes tend to be oriented along the skin lines of cleavage (Langer lines). Lesions on the back may have a characteristic “Christmas tree” whereas lesions on the upper chest may have a V-shaped pattern. There are many conditions that may mimic pityriasis rosea. Pityriasis rosea in the absence of the herald patch and its variants may pose a diagnostic challenge. The typical course is 6 to 8 weeks. In the vast majority of cases, reassurance and symptomatic treatment should suffice. Active intervention may be considered for individuals with severe or recurrent pityriasis rosea and pregnant women with the disease. Treatment options include acyclovir, macrolides (in particular, erythromycin), and ultraviolet phototherapy. If active intervention is needed, there is evidence supporting the use of oral acyclovir to shorten the duration of illness. Conclusion: Pityriasis rosea is a common, acute, self-limiting exanthematous skin disease that primarily affects children and young adults. The condition is characterized by a "herald patch" after which oval erythematous squamous lesions appear along Langer's lines of cleavage on the trunk and proximal extremities, giving it a “Christmas tree” appearance. The disease presenting in its classical form can easily be diagnosed. Clinical variants of the disease may pose a diagnostic challenge for the general pediatrician. Knowledge of the disease is essential to allow a prompt diagnosis and to avoid unnecessary investigations.

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