Rennes 15 januari 2016, Frankrijk (BIA 10-2474)
Richtlijnen en een selectie van in het nieuws en de media verschenen berichtgeving (bijgewerkt 23 juli 2016).
Tijdslijn van gebeurtenissen
- Tijdslijn (Engels), gecorrigeerde versie 29/01/2016: Chronology of the evaluation and performance of the clinical trial sponsored by BIAL laboratories and conducted by BIOTRIAL in Rennes (28/01/2016)
@Bia 10-2474 @Biotrial like for TGN 1412 all data on this drug should be made public today so that the scientific community can take action
— Adam Cohen (@adamfrederik) January 19, 2016
Autoriteiten
European Medicines Agency (EMA)
- Proposals to revise guidance on first-in-human clinical trials
Comments invited on a concept paper on changes intended to support best practices (21 July 2016). http://www.ema.europa.eu/ema/index.jsp?curl=pages/news_and_events/news/2016/07/news_detail_002572.jsp - Improving safety of first-in-human clinical trials. EMA starts EU-wide reflection on necessary changes to best practices (27 May 2016). http://www.ema.europa.eu/ema/index.jsp?curl=pages/news_and_events/news/2016/05/news_detail_002538.jsp
Frankrijk
ANSM
- Mesures de sécurisation des essais cliniques de phase I sur les volontaires sains – Point d’Information (31/03/2016) http://ansm.sante.fr/S-informer/Actualite/Mesures-de-securisation-des-essais-cliniques-de-phase-I-sur-les-volontaires-sains-Point-d-Information
- Rennes clinical trial: information on studies carried out on animals (29/02/2016). http://ansm.sante.fr/content/download/86157/1086271/version/2/file/Clinical-trial-rennes-studies-animal-fev2016.pdf
- BIAL Laboratory Clinical Trial BIA-102474-101: Publication of the Clinical Protocol. (22 January 2016). http://ansm.sante.fr/content/download/84709/1069533/version/1/file/PI_essai_clinique_bial_220116english.pdf
Vrijgegeven onderzoeksdossier
- Clinical Study Protocol N° BIA-102474-101: “A double-blind, randomised, placebo-controlled, combined single and multiple
ascending dose study including food interaction, to investigate the safety, tolerability, pharmacokinetic and pharmacodynamic profile of BIA 10-2474, in healthy volunteers.” version 1.2, 1 July 2015 (EudraCT N°: 2015-001799-24)
(Versie 2.0 te downloaden via Le Figaro, zie 21 januari 2016).
Temporary Specialist Scientific Committee (TSSC)
- Rapport final du CSST “Inhibiteurs de la FAAH” 24/03/2016 (19/04/2016) http://ansm.sante.fr/content/download/87867/1106005/version/1/file/CSST_FAAH_Rapport-Final_18-04-2016.pdf
- Relevé de conclusions du CSST Inhibiteur de la FAAH du 24/03/2016 (31/03/2016) http://ansm.sante.fr/content/download/87265/1099157/version/1/file/releve-conclusions-CSST-FAAH-230316.pdf
- Minutes of the Temporary Specialist Scientific Committee (TSSC) meeting on “FAAH (Fatty Acid Amide Hydrolase) Inhibitors” of 15/02/2016 (08/03/2016) http://ansm.sante.fr/content/download/86439/1089765/version/1/file/CR_CSST-FAAH_15-02-2016_Version-Anglaise.pdf
- Final Report by the Temporary Specialist Scientific Committee (TSSC), “FAAH (Fatty Acid Amide Hydrolase)”, on the causes of the accident during a Phase 1 clinical trial in Rennes in January 2016 (25/04/2016). http://ansm.sante.fr/content/download/88057/1108293/version/1/file/CSST_FAAH_Rapport-Final_Version-Anglaise_18-04-2016.pdf
- Temporary Specialist Scientific Committee on inhibitors of the FAAH (Fatty Acid Amide Hydrolase) – Summary of conclusion (17/02/2016). http://ansm.sante.fr/content/download/85719/1081179/version/2/file/Summary-of+conclusion-CSST-FAAH-+170216.pdf
Inspection Générale des Affaires Sociales (IGAS)
- Le rapport de l’IGAS : Enquêtes sur des incidents graves suervenus dans le cadre de la réalisation d’un essai clinique
- Rapport d’étape de l’IGAS sur l’accident survenu dans le cadre d’un essai clinique (05/02/2016). http://social-sante.gouv.fr/IMG/pdf/fevrier_2016_-_note_etape_-_accident_essai_clinique.pdf
Ministère des Affaires sociales et de la Santé
- Communiqué de presse: Suites de l’accident grave survenu à Rennes : Marisol Touraine renforce la sécurité des volontaires qui participent à des essais cliniques (23-05-2016)
- Discours de Marisol Touraine: Intervention de Marisol Touraine : Conférence de presse – Accident d’essai clinique – rapport IGAS (23-05-2016)
Sponsor en uitvoerder
BIAL
- News Release (23 May 2016)
- News Release (4 February 2016)
- News Release (19 January 2016)
- News Release (15 January 2016)
Biotrial
- Press release (23 May 2016). Biotrial strongly contests Marisol Touraine’s statement and is astonished at the behavior of the IGAS
- Press release (22 May 2016). Investigation into the accident during the clinical trial in Rennes: The three major shortcomings of the IGAS.
- Press release (25 February 2016). Rennes Clinical Trial Accident: Clarifications from Biotrial.
- Communication from Biotrial – Rennes, France (5 February 2016)
23 mei 2016
PR #Biotrial: Investigation into the accident during the clinical trial in Rennes: 3 major shortcomings of the IGAS https://t.co/s63NGjrVKt
— Biotrial (@Biotrial) May 23, 2016
#Biotrial strongly contests Marisol Touraine’s statement and is astonished at the behavior of the IGAS https://t.co/f6CL9ydZt8
— Biotrial (@Biotrial) May 23, 2016
5 februari 2016
Following the IGAS status report our organization, working processes and professionalism have been noted.
— Biotrial (@Biotrial) February 5, 2016
Regarding the alleged “major shortcomings” in the IGAS report, the items are not critical observations in relation to GCP.
— Biotrial (@Biotrial) February 5, 2016
These items have been underlined for the sole purpose of modifying legislation.
— Biotrial (@Biotrial) February 5, 2016
We have received a preliminary draft of the report from the French National Agency for the Safety of Medicines and Health Products (ANSM).
— Biotrial (@Biotrial) February 5, 2016
No critical observations were reported by the ANSM and we have responded to all comments.
— Biotrial (@Biotrial) February 5, 2016
We are confident that our responses will shed light on any remaining questions from the ANSM, and that a final report will soon be available
— Biotrial (@Biotrial) February 5, 2016
Korte achtergrond informatie
Wikipedia (korte inleiding)
- BIA 10-2474 https://en.wikipedia.org/wiki/BIA_10-2474
- Fatty acid amide hydrolase (FAAH) https://en.wikipedia.org/wiki/Fatty_acid_amide_hydrolase
- Anandamide https://en.wikipedia.org/wiki/Anandamide
Richtlijnen & documenten
UK
- Expert Group on Phase One Clinical Trials. 7 December 2006
(Chairman: Professor Gordon W. Duff). Final report of the Expert Scientific Group (ESG) which was set up following the very serious adverse reactions that occurred in the first-in-man clinical trial of TGN412 in March 2006.
- The Academy of Medical Sciences: Testing Antibody Therapies: Position Paper. 5 April 2006
- The Royal Society: Consultation response. July 2006
EU/EMA
- Strategies to identify and mitigate risks for first-in-human clinical trials with investigational medicinal products.l
- Committee for Medicinal Products for Human Use (CHMP). Guideline on strategies to identify and mitigate risks for first-in-human clinical trials with investigational medicinal products of 19 July 2007 (EMEA/CHMP/SWP/28367/07).
ICH (EU)
- ICH Q3 A (R2) Impurities in new drug substances.
- ICH Q3 C (R5) Impurities: guideline for residual solvents.
- ICH M3 (R2) Non-clinical safety studies for the conduct of human clinical trials for pharmaceuticals.
- ICH S3A Toxicokinetics: the assessment of systemic exposure in toxicity studies.
- ICH S6 (R1) Preclinical safety evaluation of biotechnology-derived pharmaceuticals.
- ICH S7B Non-clinical evaluation of the potential for delayed ventricular repolarization (QT interval prolongation) by human pharmaceuticals
- ICH S7A Safety pharmacology studies for human pharmaceuticals.
- ICH S9 Non-clinical evaluation for anticancer pharmaceuticals.
FDA
Professional organisaties
British Pharmacological Society, UK
- British Pharmacological Society (22 January 2016). Improve early access to data from catastrophic clinical trials: A statement on behalf of the British Pharmacological Society https://www.bps.ac.uk/news-events/news/society-news/articles/improve-early-access-to-data-from-catastrophic-cli
Royal Statistical Society, UK (RSS)
- RSS issues statement regarding tragic ‘first-in-man’ clinical trial. StatsLife (26 January 2016). Royal Statistical Society. https://www.statslife.org.uk/news/2660-rss-issues-statement-regarding-tragic-first-in-man-clinical-trial
- Royal Statistical Society (26 January 2016). RSS statement on the publication of the study-protocol BIA-102474-101 for the French “first-in-man” trial. http://www.rss.org.uk/Images/PDF/about/press-releases/2016-01-22-rss-statment-BIA-102474-101-french-first-trial-in-healthy-volunteers.pdf
Discussion
- Bowman Rogers, M. (2 February 2016). Will Death in French Drug Trial Lead to Tighter Phase 1 Rules? Multiple Sclerosis Discovery Forum. DOI: doi/10.7493/msdf.10.26258.1
- Bowman Rogers, M. (29 January 2016). Will Death in French Drug Trial Lead to Tighter Phase 1 Rules? Alzforum. http://www.alzforum.org/news/community-news/will-death-french-drug-trial-lead-tighter-phase-1-rules
Nieuws en media
1 juni 2016
- Miseta, E. (1 June 2016). France Tragedy Update: Bial & Biotrial At Fault; EMA Reviews Guidelines. Clinical Leader. http://www.clinicalleader.com/doc/france-tragedy-update-bial-biotrial-at-fault-ema-reviews-guidelines-0001
23, 24 & 27 mei 2016
- Blamont, M. (23 May 2016). France faults Bial and Biotrial over fatal drug trial. Reuters. http://www.reuters.com/article/us-france-health-tests-idUSKCN0YE132
- Köhler, W. (27 May 2016). Ernstige fouten bij fatale medicijnproef Frankrijk. NRC. http://www.nrc.nl/handelsblad/2016/05/27/ernstige-fouten-bij-fatale-medicijnproef-frankrijk-1624482
- Murray, S. (24 May 2016). French authorities pins blame on Bial and Biotrial for fatal drug trial. Pharmafile. http://www.pharmafile.com/news/504650/french-authorities-pins-blame-bial-and-biotrial-fatal-drug-trial
BIAL phase 1 debacle rpt: BIAL removed + preclin control data (gabapentin) frm trial brochure, hiding BIA 10-2474 minimal effect in animals.
— Jonathan Kimmelman (@KimmelmanJ) May 26, 2016
BIAL phase 1 disaster in France- crappy preclinical data given a pass by regulators & IRBs: No dose/resp; hidden + control; tiny effect size
— Jonathan Kimmelman (@KimmelmanJ) May 26, 2016
6 Mei 2016
- Toutoungi, A. (6 May 2016). French clinical trial tragedy. Dead for €1900. Eversheds International. http://www.eversheds.com/global/en/what/articles/index.page?ArticleID=en%2FHealthcare%2FFRENCH_CLINICAL_TRIAL_TRAGEDY_Dead_for_1900
20 april 2016
- Feldwisch-Drentrup, H. (20 April 2016). Expertenkommission gibt BIA 10-2474 die Schuld. Deutsche-Apotheker-Zeitung. https://www.deutsche-apotheker-zeitung.de/news/artikel/2016/04/20/expertenkommission-gibt-bia-10-2474-die-schuld-br-p-p
- Surugue, L. (20 April 2016). Rennes clinical trial: Fatal errors in dosing led to death of study participant. International Business Times. http://www.ibtimes.co.uk/rennes-clinical-trial-fatal-errors-blamed-lack-gradual-progression-volunteer-dosages-1555799
15 & 16 maart 2016
- Eddleston, M., Cohen, A.F. & Webb, D.J. (15 March 2016). Implications of the BIA-102474-101 study for review of first-into-human clinical trials. British Journal of Clinical Pharmacology
Volume 81, Issue 4, pages 582–586, April 2016 DOI: 10.1111/bcp.12920 - Experts urge more cautious dosing after fatal French drug trial. Dailymail. (16 March 2016) http://www.dailymail.co.uk/wires/reuters/article-3494253/Experts-urge-cautious-dosing-fatal-French-drug-trial.html
9 & 10 maart 2016
- Brennan, Z. (10 March 2016). ANSM Committee Delves Into Nitty-Gritty of Fatal French Phase I Trial. Regulatory Focus. http://raps.org/Regulatory-Focus/News/2016/03/10/24519/ANSM-Committee-Delves-Into-Nitty-Gritty-of-Fatal-French-Phase-I-Trial/
- Miseta, E. (10 March 2016). France Tragedy: Molecule Likely Caused “Off Target” Effect. Clinical Leader. http://www.clinicalleader.com/doc/france-tragedy-molecule-likely-caused-off-target-effect-0001
- Murray, S. (9 March 2016). French clinical trial tragedy “astonishing and unprecedented”, says report. Pharmafile. http://www.pharmafile.com/news/503311/french-clinical-trial-tragedy-astonishing-and-unprecedented-says-report
- Von Schaper, E. (10 March 2016). Bial incident raises FAAH suspicions. Nature Biotechnology 34, 223 doi:10.1038/nbt0316-223a
1 maart 2016
- Marlowe, L. (1 March 2016). Survivor of lethal French drug trial speaks out. The Irish Times. http://www.irishtimes.com/news/world/europe/survivor-of-lethal-french-drug-trial-speaks-out-1.2554593
24, 25, 26 & 29 februari 2016
- Feldwisch-Drentrup, H. (29 February 2016). Mit Paracetamol und Eiswürfeln gegen BIA 10-2474. Deutsche-Apotheker-Zeitung. https://www.deutsche-apotheker-zeitung.de/news/artikel/2016/02/29/mit-paracetamol-und-eiswurfeln-gegen-bia-10-2474
- Hawkes, N. (29 February 2016). Dogs died in studies of drug that killed man in French trial. BMJ 2016; 352 doi: http://dx.doi.org/10.1136/bmj.i1228
- Biotrial und Gesundheitsbehörde wehren sich (26 February 2016). Deutsche-Apotheker-Zeitung. https://www.deutsche-apotheker-zeitung.de/news/artikel/2016/02/26/biotrial-und-gesundheitsbehorde-wehren-sich
- MacDonald, G. (26 February 2016). Bial cannot rule out link between BIA 10-2474 and lung lesions in study dogs. In-PharmaTechnologist.com. http://www.in-pharmatechnologist.com/Regulatory-Safety/Bial-cannot-rule-out-link-between-BIA-10-2474-and-lung-lesions-in-study-dogs
- Willsher, K. (25 February 2016). French drug trial scandal: ‘dogs died in pre-clinical test’. The Guardian. https://www.theguardian.com/science/2016/feb/25/french-drug-trial-scandal-dogs-died-in-pre-clinical-test
- Jouanfigaro, A. & Mascret, D. (24 February 2016). Biotrial: de nouvelles révélations troublantes dans l’essai clinique mortel de Rennes. Le Figaro. http://sante.lefigaro.fr/actualite/2016/02/24/24667-biotrial-nouvelles-failles-beantes-dans-lessai-clinique-mortel-rennes
Bial BIA 10-2474 Study: Biotrial did not perform any of the non-clinical studies/animal tests.
— Biotrial (@Biotrial) February 25, 2016
17 februari 2016
- Feldwisch-Drentrup, H. (17 February 2016). Arzneimittelbehörde sucht Grund für Studien-Desaster. Deutsche-Apotheker-Zeitung. https://www.deutsche-apotheker-zeitung.de/news/artikel/2016/02/17/arzneimittelbehorde-sucht-grund-fur-studien-desaster
2, 3, 4 & 5 februari 2016
- French CRO under fire for trial death. European Biotechnology News (5 February 2016). http://www.european-biotechnology-news.com/news/news/2016-01/biotrial-under-fire-for-trial-death.html
- Enserink, M. (5 February 2016). French company bungled clinical trial that led to a death and illness, report says. ScienceInsider. http://www.sciencemag.org/news/2016/02/french-company-bungled-clinical-trial-led-death-and-illness-report-says
- Garde, D. (4 February 2016). French authorities still don’t know what happened in fatal drug trial. FierceBiotech. http://www.fiercebiotech.com/story/french-authorities-still-dont-know-what-happened-fatal-drug-trial/2016-02-04
- France Faults Lab for Failing to Swiftly Halt Drug Trial. (4 February 2016). Dow Jones Business News. NASDAQ.com. http://www.nasdaq.com/article/france-faults-lab-for-failing-to-swiftly-halt-drug-trial-20160204-01139
- Fassbender, M. (2 February 2016). Clear statistical reservations’ surround Bial’s fatal clinical trial. in-PharmaTechnologist.com. http://www.in-pharmatechnologist.com/Regulatory-Safety/Clear-statistical-reservations-surround-Bial-s-fatal-clinical-trial
1 februari 2016
- Miseta, E. (1 February 2016). Report: EMA Recommendations Were Not Followed In France. Clinical Leader. http://www.clinicalleader.com/doc/report-ema-recommendations-were-not-followed-in-france-0001
25 januari 2016
- Fassbender, M. (25 January 2016). Pharma fallout: Biotrial details emerge. Outsourcing-Pharma.com. http://www.outsourcing-pharma.com/Clinical-Development/Pharma-fallout-Biotrial-details-emerge
- Miseta, E. (25 January 2016). Did Poor Protocol Design Lead To The Clinical Accident In France? Clinical Leader. http://www.clinicalleader.com/doc/did-poor-protocol-design-lead-to-the-clinical-accident-in-france-0001
22 januari 2016
- Brennan, Z. (22 January 2016). FDA Conferring With EU Counterparts on Trial Fiasco in France. Regulatory Focus.
Regulatory Affairs Professionals Society. http://raps.org/Regulatory-Focus/News/2016/01/22/23956/FDA-Conferring-with-EU-Counterparts-on-Trial-Fiasco-in-France - Callaway, E. & Butler, D. (22 January 2016). Researchers question design of fatal French clinical trial. UK’s Royal Statistical Society among those demanding more information after the release of trial’s protocol. Nature doi:10.1038/nature.2016.19221
21 januari 2016
- Butler, D. & Callaway, E. (21 January 2016). Scientists in the dark after French clinical trial proves fatal. Knowledge about the drug’s structure would help researchers understand what happened. Nature 529, 263–264. doi:10.1038/nature.2016.19189
- Jouan, A. (21 January 2016). Drame de Rennes : le protocole de l’essai clinique en accusation. Le Figaro. http://sante.lefigaro.fr/actualite/2016/01/21/24518-drame-rennes-protocole-lessai-clinique-accusation
- Via Le Figaro: Clinical Study Protocol N° BIA-102474-101, version 2.0, 16 October 2015. EudraCT N°: 2015-001799-24.
20 januari 2016
- Miseta, E. (20 January 2016). Is There A Link Between The France Tragedy And Legal Highs? Clinical Leader. http://www.clinicalleader.com/doc/is-there-a-link-between-the-france-tragedy-and-legal-highs-0001
19 januari 2016
- Levy, J. (19 January 2016). French Health Minister criticises CRO’s slow response to clinical trial accident. Pharmafile. http://www.pharmafile.com/news/502427/french-health-minister-criticises-cro-s-slow-response-clinical-trial-accident
- MacDonald, G. (19 January 2016). FAAH inhibitor safety under microscope after Bial drug trial death. In-PharmaTechnologist.com. http://www.in-pharmatechnologist.com/Regulatory-Safety/FAAH-inhibitor-safety-under-microscope-after-Bial-drug-trial-death
18 januari 2016
- Christensen, J. (18 January 2016). Drug trial participant dies, 5 others hospitalized in France. CNN. http://edition.cnn.com/2016/01/18/health/france-drug-trial-participant-dies/
- Kroll, D. (18 January 2016). Scientists Speculate On What Caused The Bial Drug Testing Tragedy In France. Forbes. http://www.forbes.com/sites/davidkroll/2016/01/18/scientists-speculate-on-what-caused-the-bial-drug-testing-tragedy-in-france
- MacDonald, G. (18 January 2016). SAEs the only similarity between the BIA 10-2474 trial and ‘elephant man’ study, says MHRA. Outsourcing-Pharma.com. http://www.outsourcing-pharma.com/Clinical-Development/SAEs-the-only-similarity-between-the-BIA-10-2474-trial-and-elephant-man-study-says-MHRA
- Fassbender, M. (18 January 2016). What we know: Biotrial clinical trial tragedy. Outsourcing-Pharma.com. http://www.outsourcing-pharma.com/Clinical-Development/What-we-know-Biotrial-clinical-trial-tragedy
- Levy, J. (18 January 2016). Man left brain dead after clinical trial dies in hospital. Pharmafile. http://www.pharmafile.com/news/502401/man-left-brain-dead-after-clinical-trial-dies-hospital
16 januari 2016
- Brennan, Z. (16 January 2016). EMA Will Assess ANSM Review of Botched Clinical Trial in France. Regulatory Focus. Regulatory Affairs Professionals Society. http://raps.org/Regulatory-Focus/News/2016/01/19/23925/EMA-Will-Assess-ANSM-Review-of-Botched-Clinical-Trial-in-France/
- Enserink, M. (16 January 2016). More details emerge on fateful French drug trial. ScienceInsider. DOI: 10.1126/science.aae0247
- Mulholland, R. (16 Jan 2016). Multiple investigations launched into France drug trial that left man brain dead. The Telegraph. http://www.telegraph.co.uk/news/worldnews/europe/france/12103715/Multiple-investigations-launched-into-France-drug-trial-that-left-man-brain-dead.html
15 januari 2016
- AllTrials (15 January 2016). Comment from Ben Goldacre on the phase 1 clinical trial disaster in France. http://www.alltrials.net/news/comment-from-ben-goldacre-on-the-phase-1-clinical-trial-disaster-in-france/
- Breizh-info.com (15 January 2015). Essai thérapeutique mortel à Biotrial Rennes. Le contenu du test du Bia 10 – 2474 de Bial révélé. http://www.breizh-info.com/2016/01/15/rennes-biotrial-bialessai-therapeutique/
- Brennan, Z. (15 January 2016). France’s ANSM Investigating Trial Halted After Five Patients Hospitalized, One Brain-Dead. Regulatory Focus. Regulatory Affairs Professionals Society. http://raps.org/Regulatory-Focus/News/2016/01/15/23905/France’s-ANSM-Investigating-Trial-Halted-After-Five-Patients-Hospitalized-One-Brain-Dead/
- Chrisafis, A. (15 January 2016). French drug trial leaves one brain dead and five critically ill. The Guardian. http://www.theguardian.com/world/2016/jan/15/french-drug-trial-one-person-in-coma-and-five-critically-ill
- Enserink, M. (15 January 2016). What we know so far about the clinical trial disaster in France. ScienceInsider. DOI: 10.1126/science.aae0243
- Levy, J. (15 January 2016). Clinical trial accident leaves six critical, one ‘brain dead’. Pharmafile. http://www.pharmafile.com/news/502339/clinical-trial-accident-leaves-six-critical-one-brain-dead
- Lowe, D. (January 15, 2016). A Clinical Disaster in France. In the Pipeline. Science Translational Medicine. http://blogs.sciencemag.org/pipeline/archives/2016/01/15/a-clinical-disaster-in-france
- MacDonald, G. (15 January 2016). Biotrial run PhI study halted after patient declared brain dead. Outsourcing-Pharma.com. http://www.outsourcing-pharma.com/Clinical-Development/Biotrial-run-PhI-study-halted-after-patient-declared-brain-dead
- Sky News (15 January 2016). Man Brain Dead After Medical Trial Goes Wrong. http://news.sky.com/story/1623371/man-brain-dead-after-medical-trial-goes-wrong
