Challenges of independent assessment of potential harms of HPV vaccines

Jørgensen, Lars Nannestad; Doshi, Peter; Gøtzsche, Peter C; Jefferson, Tom

doi:10.1136/bmj.k3694

Cited by 13 publications

(20 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In May 2014, we requested the study programmes' corresponding clinical study reports from the European Medicines Agency (EMA; via its policy 0043) and obtained those reports that were freely available on GlaxoSmithKline's online trial register. We did not request clinical study reports from the manufacturers, as this would limit our ability to use and share the data [38]. In January 2017, we registered our systematic review protocol in PROS-PERO (International prospective register of systematic reviews): CRD42017056093 [37].…”

Section: Search Strategy and Study Eligibilitymentioning

confidence: 99%

“…Nearly all control participants (48,289/48,595, 99%) received an active comparator such as HPV vaccine aluminium-containing adjuvants or hepatitis vaccines. This distorted-to an unknown extent-the assessment of harms, as the trials tested an HPV vaccine vs. an active part of the same HPV vaccine (see reference [38] for additional clarification). Furthermore, serious harms were incompletely reported for 72% of the participants (68,610/95,670; see Table 1 and Additional file 2).…”

Section: Risk Of Bias Of Included Trialsmentioning

confidence: 99%

“…Furthermore, serious harms were incompletely reported for 72% of the participants (68,610/95,670; see Table 1 and Additional file 2). All 24 clinical study reports contained redactions-especially of harms-and lacked significant parts such as serious harm narratives and case report forms (except for two reports: HPV-001 and HPV-008, which, however, included less than half of the participants' case report forms) [38]. These situations are not covered by Cochrane's risk of bias tool version 2011.…”

Section: Risk Of Bias Of Included Trialsmentioning

confidence: 99%

“…Insufficient trial data access, incomplete reporting, data fragmentation and limited trial follow-up periods were major limitations. It took 3 years to obtain an incomplete subset of the eligible clinical study reports; a process which we have documented in detail elsewhere [38]. Our review is therefore limited by reporting biasthe bias that we aimed to reduce [37].…”

Section: Limitationsmentioning

confidence: 99%

“…The use of active comparators may have underestimated harms related to the HPV vaccines [38]. The aluminium-containing comparators were used, as they provided a similar appearance to that of the HPV vaccines, which enhanced blinding and decreased the risk of performance and detection bias.…”

Section: Limitations Of Harm Assessmentmentioning

confidence: 99%

See 4 more Smart Citations

Benefits and harms of the human papillomavirus (HPV) vaccines: systematic review with meta-analyses of trial data from clinical study reports

2020

Self Cite

View full text Add to dashboard Cite

Objective: To assess the benefits and harms of the human papillomavirus (HPV) vaccines. Data sources: Clinical study reports obtained from the European Medicines Agency and GlaxoSmithKline from 2014 to 2017. Eligibility criteria: Randomised trials that compared an HPV vaccine with a placebo or active comparator in healthy participants of all ages. Appraisal and synthesis: Two researchers extracted data and judged risk of bias with the Cochrane tool (version 2011). Risk ratio (RR) estimates were pooled using random-effects meta-analysis. Outcomes: Clinically relevant outcomes in intention to treat populations-including HPV-related cancer precursors irrespective of involved HPV types, treatment procedures and serious and general harms. Results: Twenty-four of 50 eligible clinical study reports were obtained with 58,412 pages of 22 trials and 2 followup studies including 95,670 participants: 79,102 females and 16,568 males age 8-72; 393,194 person-years; and 49 months mean weighted follow-up. We judged all 24 studies to be at high risk of bias. Serious harms were incompletely reported for 72% of participants (68,610/95,670). Nearly all control participants received active comparators (48,289/48,595, 99%). No clinical study report included complete case report forms. At 4 years followup, the HPV vaccines reduced HPV-related carcinoma in situ (367 in the HPV vaccine group vs. 490 in the comparator group, RR 0.73 [95% confidence interval, CI, 0.53 to 1.00], number needed to vaccinate [NNV] 387, P = 0.05, I 2 = 67%) and HPV-related treatment procedures (1018 vs. 1416, RR 0.71 [95% CI 0.63 to 0.80], NNV 75, P < 0.00001, I 2 = 45%). The HPV vaccines increased serious nervous system disorders (exploratory analysis: 72 vs. 46, RR 1.49 [1.02 to 2.16], number needed to harm [NNH] 1325, P = 0.040, I 2 = 0%) and general harms (13,248 vs. 12,394, RR 1.07 [95% CI 1.03 to 1.11], NNH 51, P = 0.0002, I 2 = 77%) but did not significantly increase fatal harms (45 vs. 38, RR 1.19 [95% CI 0.65 to 2.19], P = 0.58, I 2 = 30%) or serious harms (1404 vs. 1357, RR 1.01 [95% CI 0.94 to 1.08], P = 0.79, I 2 = 0%).

show abstract

Section: Search Strategy and Study Eligibilitymentioning

confidence: 99%

Section: Risk Of Bias Of Included Trialsmentioning

confidence: 99%

Section: Risk Of Bias Of Included Trialsmentioning

confidence: 99%

Section: Limitationsmentioning

confidence: 99%

Section: Limitations Of Harm Assessmentmentioning

confidence: 99%

See 3 more Smart Citations

Benefits and harms of the human papillomavirus (HPV) vaccines: systematic review with meta-analyses of trial data from clinical study reports

2020

Self Cite

View full text Add to dashboard Cite

show abstract

Human Papillomavirus Vaccination and Physical and Mental Health Complaints Among Female Students in Secondary Education Institutions in Denmark

et al. 2020

View full text Add to dashboard Cite

Background: Previous studies have not explored the effect of HPV vaccination on health status at longer time interval. Similarly, self-reported physical and mental health in recipients of HPV vaccine has not been studied.Objective: To evaluate whether HPV vaccination was associated with physical and mental health complaints among girls in secondary education institutions. Design: Prospective cohort study.Participants: This study used data from girls aged 15-20 years who participated in the Danish National Youth Study (DNYS) 2014. Data on HPV vaccination was retrieved from the Danish Vaccination Register. Main Measures:Participants were asked whether they had experienced headaches, stomachache, neck pain, menstrual cramps, sore throat, sadness, irritation, nervousness and sleep problems in the past six months. Key results:Of 41,333 girls, 39,145 (94.7%) received at least one dose of HPV vaccine. The most prevalent health complaint among vaccinated and not vaccinated females was "been irritable" (88.2% and 88.4%, respectively). The lowest proportion of health complaints was stomachache (49.6% in vaccinated and in 50.4% in unvaccinated girls). Regression model, adjusted for sociodemographic characteristics and health behavior, showed that HPV vaccination was associated with lower likelihood of reporting sore throat (odd ratio [OR] 0.86, 95% confidence interval [CI] 0.78-0.95) and being sad (OR 0.86, 95%CI 0.76-0.97). Similar results were observed when HPV vaccination status was analyzed according to number of doses received. Conclusion:We conclude that HPV vaccination was not associated with physical and mental health complaints among girls in secondary education institutions in Denmark after a median of 5.3 years since HPV vaccination.

show abstract

Limited data available to assess HPV vaccine safety

2018

Reactions Weekly

View full text Add to dashboard Cite

Challenges of independent assessment of potential harms of HPV vaccines

Abstract: After three years of trying to access trial data for HPV vaccines, Lars Jørgensen and colleagues find current transparency policies unfit for their purpose

Cited by 13 publications

References 18 publications

Benefits and harms of the human papillomavirus (HPV) vaccines: systematic review with meta-analyses of trial data from clinical study reports

Benefits and harms of the human papillomavirus (HPV) vaccines: systematic review with meta-analyses of trial data from clinical study reports

Human Papillomavirus Vaccination and Physical and Mental Health Complaints Among Female Students in Secondary Education Institutions in Denmark

Limited data available to assess HPV vaccine safety

Contact Info

Product

Resources

About