See; Cochrane HPV vaccine review – Table 1<\/a><\/h5>\nOur analysis reinforces the view that Cochrane HPV review is incomplete. We found an additional 25,550 females (and possibly up to 30,195 for the Cochrane HPV review\u2019s serious adverse events meta-analyses) that are eligible for the Cochrane HPV review\u2019s meta-analyses. Furthermore, we found freely available clinical study reports for 6 of the 21 studies on GlaxoSmithKline\u2019s trial register, which the Cochrane authors used data from. Clinical study reports are far more reliable than published reports (4), in particular in relation to possible serious harms. It is therefore not merely the studies the authors of the Cochrane review missed; they also missed benefits and harms data from the studies they included. In addition, the criteria that the Cochrane authors used for inclusion of data in their primary serious adverse events analysis (Analysis 7.6) are not clear: \u201cThe primary analysis for these outcomes included data that we considered to represent the most complete follow-up\u201d (3).<\/p>\n
2) The Cochrane editors\u2019 considerations on harms <\/strong><\/p>\nThe Cochrane HPV review\u2019s harms analyses (“Comparison 7\u201d) include seven meta-analyses (four of which report injection site harms) where the three most clinically important ones\u2014deaths (Analysis 7.7), serious adverse events (Analysis 7.6) and systemic adverse events (Analysis 7.5)\u2014contain errors or are incomplete.<\/p>\n
Deaths<\/u><\/strong><\/p>\nThe Cochrane HPV review’s authors found 5% (90 vs 86) more deaths in \u201cAnalysis 7.7\u201d (journal publication and registry data) vs \u201cFigure 11 (only journal publication data). We found that this discrepancy reflects the difference between the study FUTURE III\u2019s (V501-019) journal publication and registry entry (8 vs 12 deaths). We also found that the Cochrane HPV review gave an incorrect number of deaths for the VIVIANE study (HPV-015): 13 deaths in the HPV vaccine group and 5 deaths in the AlOH3<\/sub> group; according to VIVIANE\u2019s journal publication (8), there were 14 deaths in the HPV vaccine group and 3 deaths in the Al(OH)3 <\/sub>group.<\/p>\nThe Cochrane authors state that \u201cThe deaths reported in the trials had an identified cause, and none were assessed to be due to vaccination\u201d (3), but such judgements are biased, particularly in industry sponsored trials, and the analysis of deaths should be based on all events (4).<\/p>\n
Serious adverse events<\/u><\/strong><\/p>\nThere are 11% (4,758\/4,291) more serious adverse events in \u201cAnalysis 7.6\u201d (journal publication and register data) compared to \u201cFigure 10\u201d (only journal publication data). Since there were more serious adverse events and more deaths in the register entry data, we wonder why the Cochrane authors did not include register entry data for all their outcomes.<\/p>\n
We also wonder why three (possibly four) studies were not included in the Cochrane HPV review\u2019s serious adverse events meta-analyses (see Table 1). The Cochrane editors write that we \u201cclaim that the [Cochrane] review authors made an error in their reporting of serious adverse events in relation to the PATRICIA [HPV-008] study. This is not the case\u201d (1). We stated that \u201cthe Cochrane authors did not explain what the serious adverse events consisted of or whether some of them were more common in the HPV vaccine groups,\u201d (2) and gave the example that \u201cthe PATRICIA trial publication only included two thirds (1400\/2028) of the serious adverse events listed on ClinicalTrials.Gov\u201d (2). The 2,028 individual serious adverse events listed in ClinicalTrials.Gov are listed with the total denominators of randomised women for PATRICIA, for example, \u201cHeadache: participants affected\/at risk: 5\/9319 [in the HPV vaccine group] (0.05%) vs. 1\/9325 [in the hepatitis a vaccine group] (0.01%)\u201d (9), suggesting that the numbers represent participants with serious adverse events.<\/p>\n
The Cochrane editors did not consider our highly relevant observations about the incomplete reporting of serious harms (1). For example, we wrote that \u201cFUTURE I, FUTURE II and FUTURE III, which in total included 21 441 women with up to 4 years follow-up, only reported serious adverse events occurring within 14 days post-vaccination\u201d (2). The editors did not comment on how such reporting of serious adverse events for only about 3% of the trial periods (FUTURE I, II and III: [(14 days*3 vaccinations)\/(365 days*4 years)]) resulted in the Cochrane authors\u2019 judgements of \u201clow risk of bias\u201d for reporting bias (1).<\/p>\n
Both the 1st<\/sup> Cochrane review protocol from 2011 (10) and the 2nd<\/sup> protocol from 2013 (11) list the primary outcome of “serious adverse events observed after four weeks<\/u> of administration of the vaccine during the trial” (emphasis added), i.e., an incomplete reporting of serious adverse events was already a criterion at protocol stage.<\/p>\nSystemic adverse events<\/u><\/strong><\/p>\nThe Cochrane editors (1) did not comment on our criticism of the lack of studies (2)\u2014including PATRICIA (HPV-008)\u2014from the Cochrane HPV reviews\u2019 \u201cAnalysis 7.5: systemic adverse events\u201d (3). Analysis 7.5 is incomplete\u2014in particular, for Cervarix studies where the Cochrane review only included numbers for \u201csolicited general adverse events\u201d for two studies (3): HPV-009 and HPV-015, although data for such events are eligible from several additional studies, for example, HPV-001, HPV-008, HPV-013, HPV-029, HPV-030, HPV-033, HPV-035, HPV-038 and HPV-058. The inclusion of these studies could change the Cochrane review\u2019s conclusion that \u201cSystemic events with generally mild symptoms were similarly frequent in vaccinated recipients and placebo or control vaccine recipients\u201d (3). As we wrote, \u201cOn ClinicalTrials.gov, PATRICIA has 7129 vs 6557 systemic events listed under \u2018Results: Other Adverse Events (General disorders)\u2019, which in itself is a significantly increased risk: RR 1.09 (95% CI 1.07 to 1.11)\u201d (2).<\/p>\n
Furthermore, the Cochrane authors did not address that \u201csolicited general adverse events [Cervarix]\u201d only were reported 7-days post-vaccination and \u201csystemic adverse events [Gardasil]\u201d only 14-days post-vaccination (3).<\/p>\n
Assessment of safety signals<\/u><\/strong><\/p>\nThe Cochrane editors did not comment on our safety signal section (1). Some potential HPV vaccine-related harms to the nervous system\u2014or \u201cautonomic dysfunction syndromes,\u201d as the Cochrane editors described them (1)\u2014have been reported (2). The Cochrane authors should have used trial register data to investigate such safety signals; for example, if they had summarised the nervous system disorders from PATRICIA\u2019s (HPV-008) ClinicalTrials.gov list of serious adverse events (9), they would have found more serious nervous system disorders in the HPV vaccine arm: 39\/9,319 vs. 25\/9,325 in the hepatitis A vaccine arm, risk ratio 1.56 (95% CI 0.95 to 2.58). The Cochrane authors write that \u201cAll estimates of adverse effects in our review were restricted to those reported from randomised trials and therefore could not detect rare events, for which post-marketing surveillance, pharmacovigilance activities and linkage studies, joining vaccine and morbidity registries, are needed\u201d (3), but the review\u2019s results might have been different had the authors included serious adverse events on both an individual and organ system level.<\/p>\n
Additional points on the editors\u2019 harms assessment<\/u><\/strong><\/p>\nThe Cochrane HPV review (3) did not include the following harms categories that were reported in the eligible studies\u2019 clinical study reports and in some journal publications: \u201cunsolicited adverse events\u201d (Cervarix), \u201cmedically significant conditions\u201d (Cervarix), \u201cnew onset chronic\/auto-immune disease\u201d (Cervarix) and \u201cnew medical history\u201d (Gardasil), even though the Cochrane authors mention the two first categories (reported in \u201cAngelo 2014\u201d) (3).<\/p>\n
3) The editors\u2019 considerations of the trials\u2019 adjuvant and vaccine comparators<\/strong><\/p>\nThe Cochrane editors stated that \u201cThe trials comparators [sic] were unambiguously, transparently, and accurately described\u201d (1), but in the Cochrane HPV review\u2019s \u201cPlain language summary\u201d intended for lay readers, the review authors state that \u201cThe risk of serious adverse events is similar in HPV and control vaccines (placebo<\/u> or vaccine against another infection than HPV\u201d (emphasis added) (3), and the word \u201cplacebo\u201d is repeated throughout the review and all its meta-analyses, which make the review ambiguous, opaque and inaccurate, as no included trial in the review used a placebo comparator.<\/p>\n
The WHO states that using adjuvant or another vaccine as comparators instead of placebo makes it difficult to assess the harms of a vaccine (12). The HPV vaccine trials\u2019 adjuvant comparators\u2014Merck\u2019s amorphous aluminium hydroxyphosphate sulphate (AAHS) and GlaxoSmithKline\u2019s aluminium hydroxide (Al[OH]3<\/sub>)\u2014have not been tested against an inert comparator in human trials. The adjuvants\u2019 clinical properties are largely unknown; they are not regulated on their own, as regulators do not regard them as \u201cactive ingredients\u201d (13). For example, Merck\u2019s AAHS has a confidential formula and its properties are variable from batch to batch and even within batches (14). Because the HPV vaccines and their adjuvants had similar harms profiles, the manufacturers and the regulators concluded that the HPV vaccines are safe. However, this is like saying that cigarettes and cigars must be safe because they have similar harms profiles.<\/p>\nIn addition, in those trials with a non-HPV vaccine comparator, the HPV vaccine aluminium adjuvant was used in nearly all the non-HPV comparator vaccines; for example, PATRICIA\u2019s hepatitis A (Havrix) comparator contains Al(OH)3<\/sub> (only the studies HPV-032 and HPV-063 used a non-aluminium containing comparator: the hepatitis a vaccine Aimmugen). Thus, the presence of AAHS or Al(OH)3 <\/sub>in nearly all arms of the studies thwarted the harms assessment. The studies tested the vaccine antigens\u2014not the vaccines.<\/p>\nThe exclusion criteria of the Cochrane review\u2019s included trials<\/u><\/strong><\/p>\nThe Cochrane editors (1) did not consider our point that many of the Cochrane HPV review\u2019s included studies had excluded female participants \u201cif they had received the [aluminium] adjuvants before or had a history of immunological or nervous system disorders; for example, in the PATRICIA trial with 18 644 women and the FUTURE II trial with 12 167 women\u201d (2). These exclusion criteria lower the external validity of the studies and suggest that there were concerns about harms caused in such participants by the adjuvants.<\/p>\n
4) The Cochrane editors\u2019 response on the Cochrane HPV review\u2019s included outcomes<\/strong><\/p>\nThe Cochrane editors state that \u201cThe selection of outcomes for benefits was appropriate and was consistent with the World Health Organization [WHO] guidance\u201d (1).<\/p>\n
In 2004, the WHO recommended the use of cervical intraepithelial neoplasia or worse: CIN2+<\/sup>, as the primary outcome (15). CIN2+<\/sup> is a composite surrogate outcome for cervical cancer and includes CIN2, CIN3, AIS and cervical cancer. In 2014, the WHO recommended persistent HPV infection instead of CIN2+<\/sup> (16). The WHO\u2019s CIN2+<\/sup> and persistent HPV infection recommendations were approved to \u201caccelerate vaccine development and evaluation\u201d (16). Since 2014, HPV vaccines have only been required to show benefits against persistent HPV infection for getting regulatory approval as a vaccine against HPV related cancer (16).<\/p>\nAccording to the 2004 WHO recommendations, \u201cRepresentatives of industry did NOT participate in the drafting of recommendations\u201d of the use of CIN2+<\/sup> (15), but researchers with conflicts of interest did participate in the recommendations, for example, Ian Frazer\u2014the co-inventor of the HPV vaccine who \u201creceives royalties from sales of HPV prophylactic vaccines, and is a consultant for Merck, [and] GlaxoSmithKline\u201d (17). In 2014, all 17 members of the WHO group that recommended persistent HPV infection instead of CIN2+<\/sup> as the primary outcome had financial ties with the HPV vaccine manufacturers. For example, the group included two patent-holders of the HPV vaccines antigens (or \u201cvirus-like particles\u201d), who are entitled \u201cto a limited share of royalties [that] the NIH [National Institutes of Health] receives for these technologies\u201d (16).<\/p>\nOutcomes such as CIN2+<\/sup> can be difficult to interpret, and significant clinical differences can be hidden in the Cochrane HPV review\u2019s meta-analyses (3). For example, as an extreme example, if there were 5 participants with CIN2+<\/sup> in the HPV vaccine group and 10 in the comparator group, the 5 participants in the HPV vaccine group could theoretically all have cervical cancer while the 10 in the comparator group could have CIN2 lesions that often regress (18,19).<\/p>\nThe Cochrane editors (1) did not address our point that the VIVIANE study (HPV-015) included in its register entry \u201cone case of \u2018Adenocarcinoma of the cervix\u2019 and one case of \u2018Cervix cancer metastatic\u2019 \u2026 in the HPV vaccine group\u201d (2), and that the Cochrane HPV review includes a death caused by \u201cCervix cancer metastatic\u201d in the HPV vaccine group, which was not mentioned in the main text (3). The Cochrane editors (1) did not address our point that the \u201cCochrane review\u2019s 26 trials mainly included women below age 30 and used frequent cervical screening (often every 6 months) that did not reflect real-life practice (often every 3\u20135 years),\u201d which also lower the external validity of the studies (2).<\/p>\n
The Cochrane HPV review\u2019s primary analysis\u2014Analysis 1.1 that includes four trials (CVT, FUTURE I, II and PATRICIA)\u2014was of \u201cHigh\u2010grade cervical lesions in hr[high risk]HPV DNA negative women at baseline: CIN2+<\/sup> associated with HPV 16\/18 [HPV types 16 and 18 are targeted by the HPV vaccines]\u201d. Analysis 1.1 is affected by selection bias. Up to 15% of cervical cancers may not contain HPV (20), and many cervical cancers are infected with more than one HPV type. For example, in the clinical study report that we received for PATRICIA (HPV-008), 63 of the 102 of CIN2+<\/sup> cases were co-infected with two or more HPV types. In PATRICIA, if an HPV vaccine and a comparator participant were both diagnosed with CIN2+<\/sup> and positive for HPV types 31 and 33, and HPV 16\/18, 31 and 33, respectively, the HPV vaccine CIN2+<\/sup> case would be assigned as caused by non-vaccine types (31 and 33) and excluded from the analyses (such as Analysis 1.1), while the comparator case would be caused by HPV 16\/18 (HPV vaccine types) and included in the analyses; even though HPV types 31 and 33 could have caused the CIN2+<\/sup> lesions in both participants. The Cochrane review\u2019s analyses of HPV infection (\u201cComparison 4, 5 and 6\u201d) include 21 meta-analyses that all analyse infection of HPV vaccine types (i.e., HPV types 6, 11, 16 and 18)\u2014not an infection of any HPV type, which would decrease confounding by HPV co-infection.<\/p>\nAnother issue with Analysis 1.1 (3) is the large proportion of excluded females: 23,676 participants were included, but the included four studies (CVT, FUTURE I, II and PATRICIA) randomised 43,732 participants, so 46% females were excluded. The Cochrane authors did not mention that FUTURE I, II and PATRICIA\u2014that contained 49% (36,266\/73,428) of the Cochrane review\u2019s sample (3)\u2014were stopped early when HPV 16\/18-related CIN2+<\/sup> was significantly reduced for the HPV vaccine populations. Trials stopped early for benefits are known to exaggerate the effects by 29% on average compared to completed trials of the same intervention (21).<\/p>\nThe majority (24 of 31) of the Cochrane HPV review\u2019s meta-analyses of histological outcomes (\u201cComparison 1, 2 and 3\u201d) consider cervical lesions associated with HPV vaccine types (3). A less biased meta-analysis of cervical lesions is \u201cAnalysis 3.7: High\u2010grade cervical lesions in women regardless of baseline HPV DNA status: Any CIN2+ irrespective of HPV types, at least 1 dose.\u201d The Cochrane HPV review\u2019s primary analysis\u2014Analysis 1.1\u2014is much more statistically significant than Analysis 3.7 (3): risk ratio 0.01 (95% CI 0.01 to 0.05) vs. 0.79 (95% CI 0.65 to 0.97), i.e., a ratio of relative risks of 0.01 (95% CI 0.006 to 0.03), which may reflect the selection bias in Analysis 1.1.<\/p>\n
Both the 1st<\/sup> Cochrane HPV review protocol from 2011 (10) and the 2nd<\/sup> protocol from 2013 (11) list “Invasive cervical cancer” as a primary outcome. The protocols state that the Cochrane authors \u201cwill contact study authors or data owners to request data on the outcomes that were not reported\u201d (11), which they did not do for invasive cervical cancer. Also, \u201cIf data are reported for grouped end points, we will contact trial authors or data owners to request data on the separated outcomes\u201d (11), which the authors did not do for CIN2+<\/sup> and CIN3+<\/sup>. But the Cochrane authors could have looked in the journal publications; for example, CIN3 irrespective of HPV type in intention-to-treat populations was reported in FUTURE I (22) (\u201c79\/2723 [in the HPV vaccine group] vs. 72\/2732 [in the AAHS group]\u201d) and FUTURE II (23) (\u201c127\/6087 [in the HPV vaccine group] vs. 161\/6080 [in the AAHS group]\u201d: in total 206\/8,810 vs. 233\/8,812; risk ratio 0.91 [95% CI 0.66 to 1.27]).<\/p>\nFurthermore, the Cochrane authors write that \u201cNo results were found for the outcomes any [sic] CIN3+ or AIS+ irrespective of HPV type\u201d (3). If the Cochrane authors had looked in the freely available clinical study reports on GlaxoSmithKline\u2019s trial register that the authors assessed, they would have found the outcomes CIN3+<\/sup> irrespective of HPV type for PATRICIA (86\/9,319 vs. 158\/9,325) and HPV-032\/063 combined (9\/464 vs. 14\/463).<\/p>\n5) The Cochrane editors\u2019 assessment of the Cochrane authors\u2019 conflicts of interest<\/strong><\/p>\nThe Cochrane editors state that \u201cThe review was compliant with Cochrane\u2019s current conflict of interest policy\u201d (1). If that is the case, we believe Cochrane should reconsider its policy.<\/p>\n
The HPV vaccines are expensive blockbuster vaccines generating billions of dollars of revenue (24), and the Cochrane review ought, therefore, to have been independent of any financial conflicts of interests.<\/p>\n
The Cochrane editors are confident that the Cochrane authors have no relevant conflicts of interest (2). We do not agree. For example, the Cochrane HPV review\u2019s first author, Professor Marc Arbyn\u2014who, according to the Cochrane review (3), only \u201creceived travel grants from MSD\u2010Sanofi\u2010Pasteur and GSK, (ceased in 2008)\u201d\u2014was until 2008 on GlaxoSmithKline\u2019s advisory board: \u201cMarc Arbyn (GSK advisory Board (interrupted in 2008))\u201d) (25); in 2011, \u201cEUROGIN covered his [Marc Arbyn\u2019s] travel and lodging expenses \u2026 EUROGIN conferences are financially supported by a range of pharmaceutical companies with an interest in cervical cancer\u201d (26); in 2014, \u201cMarc Arbyn’s research unit at The Scientific Institute of Public Health received research support not exceeding 48,000 Euros from MSD-Sanofi Pasteur [co-manufacturer of Gardasil] for a surveillance study of the effects of HPV vaccination in Belgium (SEHIB study) … His [Marc Arbyn\u2019s] unit has also received research support from BD, Bio-Greiner, Abbot, and Cepheid for validation studies of HPV genotyping tests (through the VALGENT studies, valued at 21,000, 21,000 & 38,000\u20ac respectively)\u201d (27); and in 2018, Marc Arbyn is on the EUROGIN programme committee where Merck is a platinum sponsor (28). The Cochrane review\u2019s last author, Dr. Markowitz is sponsored by Merck via Medscape (\u201csponsored by the manufacturer of the quadrivalent vaccine (\u201csupported by an independent educational grant from Merck\u201d) (29).<\/p>\n
The Cochrane editors (1) do not think that the Costa Rica trial (\u201cCVT\u201d, aka HPV-009) was industry funded, and they refer to its publication in JAMA that states that the trial was “funded by the NCI (grant N01-CP-11005).\u201d The editors write, with reference to JAMA, that \u201cVaccine was provided for our trial by GSK [GlaxoSmithKline] Biologicals, under a Clinical Trials Agreement with the NCI” (1). GlaxoSmithKline also provided support for aspects of the trial associated with regulatory submissions under \u201cFDA BB-IND 7920\u201d (30). We consider this industry funding.<\/p>\n
6) The Cochrane editors\u2019 assessment of the media coverage<\/strong><\/p>\nThe Cochrane editors (1) did not comment on our note that \u201cTwo of the experts had financial conflicts of interest with the HPV vaccine manufactures \u2026 [and that] No expert criticised the review\u201d (2).<\/p>\n
The editors (1) write that \u201cpress coverage could be made more explicit on our organizational websites and other communications, essentially noting that these opinions represent personal perspectives from a range of contributors and do not reflect the views or policies of Cochrane\u201d (1). We agree, but stress that Cochrane\u2019s press officer ought to only include researchers with no financial conflicts of interest.<\/p>\n
7) <\/strong>The Cochrane editors appear to advocate scientific censorship<\/strong><\/p>\nThe Cochrane editors wrote that \u201cScientific debate is to be welcomed, and differences of opinion between different Cochrane ‘voices’ is not unexpected. However, public confidence may be undermined, unnecessary anxiety caused, and public health put at risk, if that debate is not undertaken in an appropriate way. This is especially true when such debates take place in public. There is already a formidable and growing anti-vaccination lobby. If the result of this controversy is reduced uptake of the vaccine among young women, this has the potential to lead to women suffering and dying unnecessarily from cervical cancer.\u201d We believe that our criticism of the Cochrane review is appropriate and has general interest. We believe that providing an assessment of all the evidence reduces uncertainty and allows the public to make informed decisions based on the benefits and the harms of HPV vaccines. Debates over sources of evidence must take place in public, especially when public health interventions are at stake.<\/p>\n
8) Conclusion <\/strong><\/p>\nWe did not \u201csubstantially overstate\u201d (1) our criticisms of the Cochrane HPV vaccine review (2). The Cochrane editors substantially ignored several of our criticisms. The Cochrane HPV review is still incomplete and ignores important evidence of bias.<\/p>\n
The Cochrane editors stated that \u201cSome of the criticisms will inform the next version of this Cochrane Review and the planned review of comparative studies of HPV vaccines,\u201d and that the editors \u201crecognize public concerns about the aluminium-based adjuvants\u201d (1).<\/p>\n
The editors also stated that \u201creliance on the published reports in scientific journals may introduce bias due to incomplete and selective reporting\u201d (1). We agree and remind the Cochrane editors that the Cochrane review on neuraminidase inhibitors substantially changed its conclusions after it got updated and became based on clinical study reports instead of journal publications (31).<\/p>\n
With our analysis (2), we have contributed to a scientific debate in an area that is complex and biased. The Cochrane HPV review authors stated that they will make a \u201cRequest for non\u2010published available data\u201d such as clinical study reports that \u201cwill be integrated in future updates of the review\u201d (3). We can offer them these data, which we have used for our own systematic review that we have submitted for publication.<\/p>\n
Article info<\/strong><\/p>\nConflicts of interest<\/u>: LJ and PCG have no conflicts of interest to declare. TJ was a recipient of a UK National Institute for Health Research grant for a Cochrane review of neuraminidase inhibitors for influenza. In addition, TJ receives royalties from his books published by Il Pensiero Scientifico Editore, Rome and Blackwells. TJ is occasionally interviewed by market research companies about phase I or II pharmaceutical products. In 2011-13, TJ acted as an expert witness in litigation related to the antiviral oseltamivir, in two litigation cases on potential vaccine-related damage and in a labour case on influenza vaccines in healthcare workers in Canada. He has acted as a consultant for Roche (1997-99), GSK (2001-2), Sanofi-Synthelabo (2003), and IMS Health (2013).In 2014 he was retained as a scientific adviser to a legal team acting on oseltamivir. TJ has a potential financial conflict of interest in the drug oseltamivir. In 2014-16, TJ was a member of three advisory boards for Boerhinger Ingelheim. TJ was holder of a Cochrane Methods Innovations Fund grant to develop guidance on the use of regulatory data in Cochrane reviews. TJ was a member of an independent data monitoring committee for a Sanofi Pasteur clinical trial on an influenza vaccine. Between 1994 and 2013, TJ was the coordinator of the Cochrane Vaccines Field. TJ was a co-signatory of the Nordic Cochrane Centre Complaint to the European Medicines Agency (EMA) over maladministration at the EMA in relation to the investigation of alleged harms of HPV vaccines and consequent complaints to the European Ombudsman. TJ is co-holder of a John and Laura Arnold Foundation grant for development of a RIAT support centre (2017-2020) and Jean Monnet Network Grant, 2017-2020 for The\u00a0Jean Monnet Health Law and Policy Network. TJ is an unpaid collaborator to the project Beyond Transparency in Pharmaceutical Research and Regulation led by Dalhousie University and funded by the Canadian Institutes of Health Research (2018-2022).<\/p>\n
Authors’ experience<\/u>: PCG has co-authored 17 Cochrane reviews, including several reviews based on clinical study reports. TJ has co-authored 17 Cochrane reviews including the first Cochrane review that used clinical study reports. LJ has co-authored several articles on the HPV vaccines.\u00a0<\/u><\/p>\n
Authors’ contributions<\/u>: LJ wrote the first draft. LJ, PCG and TJ contributed to the conception, drafting,<\/p>\n
critical revision for important intellectual content and the final approval of the article.<\/p>\n
Acknowledgements<\/u>: We would like to thank the Cochrane editors for taking our analysis into consideration and the BMJ-EBM editors for allowing us to respond via their journal.<\/p>\n
Provenance and peer review<\/u>: Commissioned; not externally peer-reviewed.<\/p>\n
Copyright information<\/u>: \u00a9 Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.<\/p>\n
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<\/p>\n","protected":false},"excerpt":{"rendered":"
J\u00f8rgensen,\u00a01G\u00f8tzsche\u00a01\u00a0and Jefferson\u00a01\u00a0\u00a0consider their analysis was appropriate and that the Cochrane editors substantially ignored several of their criticisms. 1Nordic Cochrane Centre, Rigshospitalet 7811, Tagensvej 21, 2100 Copenhagen, Denmark. Originally posted at: The Cochrane HPV vaccine review was incomplete and ignored important evidence of bias: Response to the Cochrane editors. at BMJ EBM on 17 September […]<\/p>\n
Read More…<\/a><\/p>\n","protected":false},"author":1,"featured_media":1818,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[14373],"tags":[],"class_list":["post-1811","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-evidence-synthesis"],"yoast_head":"\nResponse to Cochrane editors: J\u00f8rgensen, G\u00f8tzsche and Jefferson - BMJ EBM Spotlight<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/blogs.bmj.com\/bmjebmspotlight\/2018\/09\/23\/response-to-cochrane-editors-jorgensen-gotzsche-and-jefferson\/\" \/>\n<meta property=\"og:locale\" content=\"en_GB\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Response to Cochrane editors: J\u00f8rgensen, G\u00f8tzsche and Jefferson - BMJ EBM Spotlight\" \/>\n<meta property=\"og:description\" content=\" J\u00f8rgensen,\u00a01G\u00f8tzsche\u00a01\u00a0and Jefferson\u00a01\u00a0\u00a0consider their analysis was appropriate and that the Cochrane editors substantially ignored several of their criticisms. 1Nordic Cochrane Centre, Rigshospitalet 7811, Tagensvej 21, 2100 Copenhagen, Denmark. 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