DIAlog AI: Part Two: Cookes' New Position Predecessor’s Past: Drug Safety Debacle Leads to Death of a WhistleBlower Due to Bias & an Up-to-Date Check Up of Drug Safety Personnel

Dial-a-Docs Dirty Dozen 4 to 6: Chronological Citations from the Cochrane Crisis over the HPV Vaccine Review; Rapporteurs to Raconteurs; Co-chairs Co-llaborations & watch out for UN/EU Revolving Door.

Jan 30, 2023

Dial-a-Docs 4) Chronological Citations from Emer’s Predecessor’s Prevaricating patents to the decade long debacle of the Cochrane Crisis of the HPV vaccine review due to BIAS.

1 - Kelly’s Eye

“A potential safety signal with the HPV vaccines in relation to two neurological conditions, Postural Orthostatic Tachycardia Syndrome (POTS) and Complex Regional Pain Syndrome (CRPS) was raised by the Danish Health and Medicines Authority in July 2015. This Article-20 referral procedure was triggered where the EMA was asked to give an opinion on whether there was evidence of a causal association between HPV vaccines and CRPS and/or POTS” https://www.ema.europa.eu/en/documents/referral/hpv-vaccines-article-20-procedure-notification_en.pdf

2 – One Little Duck

At the conclusion of the referral procedure in November 2015, the EMA opinion was formalised in an Assessment Report, which found no evidence of a causal association between HPV vaccines and CRPS and/or POTS.

“Taking into account the totality of the available data, the PRAC concluded that the available evidence does not support that HPV vaccines cause CRPS or POTS...

..The PRAC adopted, by consensus, the maintenance of the marketing authorisations” https://www.ema.europa.eu/en/documents/minutes/minutes-prac-meeting-3-6-november-2015_en.pdf

3 - Cup of Tea

On the 26th May 2016, Professor Peter C. Gøtzsche, Director of the Nordic Cochrane Centre along with others, filed an official complaint with the EMA about how the Agency had conducted the HPV safety referral procedure. https://web.archive.org/web/20161205121429/http://nordic.cochrane.org/sites/nordic.cochrane.org/files/public/uploads/ResearchHighlights/Complaint-to-EMA-over-EMA.pdf

4 - Knock at the door

EMA response to their complaint dated 17 June 2016: https://www.ema.europa.eu/en/documents/other/ema-response-nordic-cochrane-letter-human-papillomavirus-hpv-vaccines-conflict-interest-issues_en.pdf

5 - Man Alive

Dissatisfied with this EMA response Professor Gøtzsche and the signatories to the initial complaint to the EMA escalated their complaint to the European Ombudsman on the 10th Oct 2016 , supported by several eminent scientists. https://cijepljenje.info/wp-content/uploads/2016/10/Complaint-to-ombudsman-over-EMA.pdf

6 - Tom Mix

“European Ombusdman’s Case opened: “The European Medicines Agency’s handling of the so-called referral procedure of a particular pharmaceutical product CASE 1475/2016/JAS - OPENED ON Monday | 05 December 2016” https://www.ombudsman.europa.eu/en/opening-summary/en/72812

7 - Lucky 7

“European Ombusdman’s Case Description 1475/2016/JAS : Strasbourg, 05/12/2016: In Oct 2016, the Ombudsman received a complaint alleging that the European Medicines Agency had not dealt properly with a so-called referral procedure related to a pharmaceutical product and alleging a lack of transparency. The complaint does not concern the safety of the product…… The Ombusdman is not in a position to question scientific conclusions made by the competent scientific bodies.” http://www.ombudsman.europa.eu/en/case/en/48828

8 - Garden Gate

“European Ombusdman’s Case Decision: 1475/2016/JAS on the European Medicines Agency’s handling of the referral procedure relating to human papillomavirus (HPV) vaccines DECISION CASE 1475/2016/JAS - DECISION ON Monday | 16 October 2017 - INSTITUTION CONCERNED European Medicines Agency (No maladministration found).” https://www.ombudsman.europa.eu/en/decision/en/84736

9 - Doctor’s Orders

“July 2018 Peter C Gøtzsche: The Cochrane HPV vaccine review was incomplete and ignored important evidence of bias” https://www.researchgate.net/publication/326661408_The_Cochrane_HPV_vaccine_review_was_incomplete_and_ignored_important_evidence_of_bias

10 – Theresa’s Den

“Sept 2018 Peter C Gøtzsche: Challenges of independent assessment of potential harms of HPV vaccines” https://pubmed.ncbi.nlm.nih.gov/30249615/

11 – Legs Eleven

“Oct 2018 Raghavan Srivatsan: Storm in a teacup? General implications of the Cochrane crisis: What is at stake? On the one hand, if the Cochrane Board is right, Gøtzsche’s pronouncements, under the garb of Cochrane authority, unethically mislead doctors and the people at large by misinforming them about false ﬂaws in these drugs, thus putting many young girls at risk of preventable cervical cancer. On the other hand, if Gøtzsche et al are right, the Cochrane reviews of the HPV vaccines are faulty. These vaccines can cause serious iatrogenic disability: postural orthostatic tachycardia syndrome (POTS) and complex regional pain syndrome (CRPS), are two documented side-effects of the vaccine (6). The disagreement between Gøtzsche and the Board is regarding the relative risk and beneﬁt. Gøtzsche’s charge is that these problems arise because the Cochrane Review Board which had started out as a noble institution to ensure the truth of medical research is corrupted by the pressure of pharma. So, the storm in this teacup has some potentially serious repercussions on our lives. For example, doctors blithely recommend the use of HPV vaccines ignoring (or perhaps in genuine ignorance of) doubts about their side effects (7). How do we decide what to do?” https://www.researchgate.net/publication/328633153_Storm_in_a_teacup_General_implications_of_the_Cochrane_crisis

12 – One Dozen

“July 2019 Peter C. Gøtzsche: Death of a Whistleblower and Cochrane’s Moral Collapse” https://s3.amazonaws.com/crossfitpubliccontent/Gotzsche_DDC_Lecture.pdf

Dial-a-Docs 5) Un News Flashback Sep 2018

“Ebola, fake drugs and other 21st century challenges for health regulators Dr. Cooke explained how regulators play a vital role in strengthening global collaboration - and ensuring patient safety”

Source:

https://news.un.org/en/audio/2018/09/1018741

Dial-a-Docs 6a) Up-to-date check up of Drug Safety Personnel from Original HPV Safety Signal Decade Long Debacle

Gliding right along past Guido Rassi Emer’s predeccessor’s prevaricating patents and revolving door partner with the WHO and the mysterious case of the Cochrane mis-identity of the Replicating PRAC Rapporteur Julie Andrews as the Welsh Honourable.…..

We have some co-incidental signals of interest:

Jean-Michel Dogne: Still doggedly PRACtising his craft Rapporteur’ing for the EMA at the Pharmacovigilance Risk Assessment Committee (PRAC) & promoted in 2020: “Thanks to his recognised expertise in vaccine pharmacovigilance, he will participate to the formulation of scientific advice to the WHO on general vaccine safety issues of potential global importance”

DIAl-a-Docs 6b) From MD Researcher and Rapporteur to Raconteur at UPpsala UNder everyones RADAR WHO likes tweets on BERT and Markets Drug Safety PRACtises

Qun-Ying Yue MD UMC at the “International Society of Pharmacovigilance (ISoP), Pharmacogenomic Special Interest Group(PGx SIG), Uppsala Monitoring Centre(UMC), Bredgränd 7, 753 20 Uppsala, Sweden": The new PGx SIG at the ISoP will contribute to the goal of identifying patients at risk and to improve the benefit-risk balance of drug treatment in genomic sub-populations..”

Source:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8184708/#

Uppsala Monitoring Centre (UMC) Hello Researcher: RESEARCH / 10 APRIL 2020:

“i’m working through a couple of interesting things. The first is the book Pharmacovigilance: Critique and Ways Forward, edited by Ralph Edwards and Marie Lindquist – UMC’s former and current director, respectively…...

….The potential use of chloroquine on the novel coronavirus SARS-CoV-2 in an urgent situation is an example… to be very clear that the current available evidence of the drug’s efficacy and safety for treating COVID-19 is limited and relatively weak….

…We also need to advise doctors and patients very clearly that chloroquine can lead to serious cardiac problems in some patients – it is known to cause QT interval prolongation – and other side effects, particularly with high dose. In fact, there have been some media reports of serious poisoning cases arising out of self- experimentation.”

Source:

https://www.uppsalareports.org/articles/hello-researcher-what-are-you-reading-qun-ying-yue/

May 2021: “Listen up: Every outlier is still a patient in need of safe treatment.”

Sources:

https://isoponline.org/special-interest-groups/pharmacogenomics/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8184708/

https://www.uppsalareports.org/articles/pharmacogenomics-group-aims-to-refine-patient-safety-options/

Bart Cobert: “Pharmacovigilance, Drug, Safety and Regulatory Affairs Author & Expert: Nov 28 2012: Vigibase: This is a very large (probably the largest) drug safety database in the world. It has over 7 million individual case safety reports from 100 plus countries. It covers primarily marketed products and receives its data primarily from individual health agencies worldwide. Companies do not submit cases directly. What is most interesting and useful is that the UMC provides safety data from Vigibase to companies, governments and other interested parties. They are quite refreshingly frank in stating that they help pharmaceutical companies “extract valuable information about the safety profile of their drug products as well as their competitors.’””

Source:

https://lifesciencescare.hcltech.com/blog/the-uppsala-monitoring-centre-umc/

Uppsala Monitoring Centre, the WHO Collaborating Centre for International Drug Monitoring: “Drug Safety Matters brings you the best stories from the world of pharmacovigilance. Through in-depth interviews with our guests, we cover new research and trends, and explore the most pressing issues in medicines safety today”.

#How do we change behaviour around antimicrobial resistance April 2021 #10 Tailoring drug therapy to your genes – Qun-Ying Yue July 2021 #Uppsala Reports Long Reads – Convincing the vaccine hesitant August 2021 #12 Improving signal detection with vigiGroup –Jim Barrett & Joe Mitchell” 16 Dec 2021

“….Busy filtering vigibase now has 29 million reports….

…No technique is perfect ..we were able to identify known & expected signals of the vaccines, also as reporting developed we were seeing clusters to the adverse events became more apparent after the initial marketing of the vaccines we saw, for example, .. clusters relating too localised delayed reactions around the vaccination site OR myocarditis and inflammation of the heart muscle which have been sort of discussed at length by stakeholders and are recognised as side effects” 16 Dec 2021

“Appendicitis as a possible safety signal for the COVID-19 vaccines Joseph Mitchell /Qun-Ying Yue: …has been suggested as an adverse event of special interest post-vaccination against COVID-19 after a numerical increase in the vaccine arm of a clinical trial. The case series may be affected by differences in global patterns of reporting, and it is not possible to prove nor disprove causality from this case series. Global longitudinal studies are required to clarify any possible relationship”.

Sources:

https://www.drugsafetymatterspod.org/618871

https://pubmed.ncbi.nlm.nih.gov/34746743/

“… vigiGroup, UMC’s novel consensus clustering algorithm developed to identify groups of reports with similar adverse events, complementing existing data screening methods in pharmacovigilance…. “Consensus clustering for case series identification and adverse event profiles in pharmacovigilance” was published in Artificial Intelligence in Medicine” Feb 2022

Source:

https://uppsalareports.org/articles/vigigroup-in-action-new-method-identifies-groups-of-related-reports/

International Society of Pharmacovigilance Committed to safer use of medicines worldwide Intelligent Automation in Pharmacovigilance 2022 6th ISoP Seminar (Hybrid event) 5-6December 2022 In-person venue: Cambridge Biogen Campus: Hybrid Meeting format: The Boston seminar is a hybrid event, giving you the option to attend in-person or virtually using the ISoP Zoom platform (streamed live from Boston (EST time)).

Eva-Lisa Meldau (Data Scientist): “Safety monitoring and signal detection for the novel COVID-19 vaccines Eva-Lisa Meldau (Data Scientist, Uppsala Monitoring Centre): Automated redaction of narratives from the UK Yellow Card Scheme using BERT” Nov 2022

Sources:

https://twitter.com/ISoPonline/status/1599863359804874752?s=20

https://isoponline.org/wp-content/uploads/2022/11/2022-ISoP-Boston-Seminar-final.pdf

DIAl-a-Docs 6c)To the CO-Chair’s CONvenient DIA COllaborations, family DOCTOT and circling back co-incidentally to Emer Cookes Co-Chair at DARWIN EU Big Data HQ as Farma Industry Observer - observed in turn by LSTMH at Imperial

“Álmath was the first Vice Chair of EMA's PRAC and served from 2012-2018…

…called to the Bar of Ireland in 2018 and practiced in Commercial Law prior to joining AbbVie's Global Regulatory Policy and Intelligence team as Director in 2020…

….global policy lead for Patient Focused Drug Development and Pharmacovigilance and European lead for Real World Evidence (RWE), Digital Health and clinical pharmacology”

Source:

https://www.diaglobal.org/en/conference-listing/meetings/2023/02/dia-middle-east/speakers

“DIA Vision: is your essential partner in catalyzing knowledge creation and sharing to accelerate healthcare product development….

…Today, professionals from 80 countries continue to engage with DIA through our membership network..

…defines its thought leadership to span Translational Science and Medicine, Regulatory Science, Patient Engagement, and Value & Access…

..recognized as an authorized training partner of the International Council on Harmonization (ICH)…facilitates China’s inclusion as official ICH member. launches tailored programs ..Drug Discovery Innovation conference in China…

2019 Report: In the gene-editing space, we fostered critical conversations among stakeholders at a various DIA meetings, bringing researchers and leading gene editing companies together with regulators to discuss manufacturing processes and create efficient regulatory pathways for cutting-edge gene therapies….

…In collaboration with the Boston Consulting Group (BCG) Market Access Roundtable, the Sustainability of Healthcare Funding initiative progressed further, studying the emerging payment models—ranging from annuity payments, as promoted by companies such as Novartis, to subscription models—set forward by several US States.”

Sources:

https://globalforum.diaglobal.org/annualreport-2019/

https://www.diaglobal.org/en/about-us

AlMath First cousins Fergal and Padraig: “learned countless important lessons, many of which became guiding principles for them in business… Highlighting …just one first cousin from .. family, to exemplify:

- From Almath Spooner, who claimed all 6 prizes in her Kings' Inn Legal Studies class whilst simultaneously working full-time as the Pharmacovigilance and Risk Management Lead with the Health Products Regulatory Authority Ireland (not to mention representing the European Union at the ICH, and Vice-Chairing the European Medicine Agency's PRA Committee at the very same time);

Padraig and Fergal realised you can always do more….

An abbreviation of DOC's Tools Of Trade (whilst simultaneously being a portmanteau of "Doctor" and "Robot"), we're an intrinsically motivated Health Informatics Consortium dedicated to the promotion of Best Practice.

Clinical Diagnosis Aids provide solutions in disease areas such as Neurology, Cardiology, COPD, Geriatric Medicine, Diabetes and Pain Management.

Working in conjunction with Healthcare giants such as the World Health Organisation, SINTEF, AO Foundation, GOLD and the Royal College of Physicians; elegantly crafted native Apps, which pre-existing tools cannot match for accuracy, efficiency or usability, are made available for download.”

Sources:

http://www.tailteann.org/family-values

https://www.doctot.com/

GOLD 2019: “GLOBAL INITIATIVE FOR CHRONIC OBSTRUCTIVE LUNG DISEASE (GOLD) DISCLOSURE OF FINANCIAL INTEREST” : See Sources too many disclosures to list here.

GOLD April 2020 Example:

Sources:

https://goldcopd.org/wp-content/uploads/2020/03/GOLD-2019-Disclosures_Board-and-SC.pdf

https://erj.ersjournals.com/content/54/1/1900914.long

https://www.eurekalert.org/news-releases/720790

MedNous editor [Victoria English] on the basis of interviews with Peter Arlett of the EMA and Álmath Spooner of Efpia & a literature search [References: 1. Discussion paper: use of patient disease registries for regulatory purposes, EMA/644749/2018. 2. National Institute for Health and Care Excellence, Glossary, www.nice.org.uk] ©2022 Evernow Publishing Ltd APRIL 2022:

Peter Artlett DARWIN EU EMA project team representative:

“The role of industry in the DARWIN EU project is central because it is their products that will be evaluated under the new procedures. The European pharmaceutical industry federation Efpia has an OBSERVER role on the project’s advisory board. The Efpia representative is Álmath Spooner, director of regulatory policy and intelligence at AbbVie Inc. …Dr Spooner identified four principles that industry would like to see …

..first is transparency .. clarity on how we go from data to evidence… algorithms and methods are being used,….”

..Second, well established use cases ..develop confidence in the platform

..third, to learn from and share with US also expanding the use of real-world evidence in regulatory decision making.

..Finally, industry would like regulators to take the opportunity presented by the new data to reconfigure scientific advice into a more iterative scientific dialogue”.