Essais Cliniques et COVID-19

Accueil Essais Cliniques et COVID-19



Mise à jour le 25 mars 2020 à 19h00

Pour ses propres besoins, Sunnikan maintient une Base de Connaissances d’analyse réglementaire portant sur plus de 800 thèmes relatifs à la recherche clinique et la pharmacovigilance.

Dans le contexte actuel, Sunnikan met à votre disposition l’analyse réglementaire relative à l’impact de l’épidémie de Covid-19 sur les essais cliniques.

Merci par avance de nous remonter vos commentaires pour améliorer cette page mise au service de tous !

Sélectionnez un ou plusieurs pays (Ne fonctionne pas avec Internet Explorer) :

     

Sites Internet et contacts

       
  fr France ANSM : questions.clinicaltrials@ansm.sante.fr en mentionnant COVID-19 dans le sujet de votre message
DGS : ccs-pole-recherche@sante.gouv.fr
  eu Europe Eudralex – Volume 10
  DE Allemagne COVID@bfarm.de (Questions seulement, ne pas soumettre les demandes d’autorisation ou d’amendements par cette adresse)
  BG Bulgarie clintrialsquestions@bda.bg / 0894195544
       
     

Référentiels applicables

       
2020 eu Europe Guidance on the Management of Clinical Trials during the COVID-19 (Coronavirus) pandemic, EMA,
Updated on 24 March 2020
2020 UK Royaume-Uni MHRA Good Practice (GxP) inspections during the COVID19 outbreak, MHRA, Great-Britain, 23 March 2020
2020 fr France FAQ – Covid 19 – Essais cliniques en cours, ANSM, France, 20 mars 2020 QnA – Covid 19 – Ongoing clinical, ANSM, France, 20 March 2020
2020 fr France Essais cliniques : procédures accélérées pour l’évaluation des traitements du COVID-19 et recommandations aux promoteurs sur les essais en cours – Point d’information, ANSM, France, 20 mars 2020
2020 eu Europe Guidance to sponsors on how to manage clinical trials during the COVID-19 pandemic – Press Release – EMA, 20 March 2020
2020 DE Allemagne  « Genehmigungsverfahren », BfARM Internet site, Germany, 19 März 2020
2020 BG Bulgarie Recommandations aux commanditaires concernant la conduite des essais cliniques dans le cadre du risque complexe de Covid-19 d’une déclaration de l’état d’urgence dans le pays, BDA, Bulgarie, 18 mars 2020 (Traduction) Bulgare ПРЕПОРЪКИ КЪМ СПОНСОРИТЕ ОТНОСНО ПРОВЕЖДАНЕТО НА КЛИНИЧНИ ИЗПИТВАНИЯ ВЪВ ВРЪЗКА С УСЛОЖНЕНАТА ОБСТАНОВКА ОТ ПОВИШЕН РИСК ОТ COVID-19 И ОБЯВЕНОТО ИЗВЪНРЕДНО ПОЛОЖЕНИЕ В СТРАНАТА, BDA, Bulgaria, 18  March 2020
2020 us Etats-Unis Coronavirus (COVID-19) Update: FDA Issues Guidance for Conducting Clinical Trials, FDA, USA, 18 March 2020
2020 DK Danemark Fast-track Approval of Clinical Trials investigating COVID-19, Danish Medicines Agency, Denmark, 17 March 2020
2020 UK Royaume-Uni COVID-19: Guidance for sponsors, sites and researchers V2, MHRA, United Kingdom, 17 March 2020
2020 eu Europe Call to pool research resources into large multi-centre, multi-arm clinical trials to generate sound evidence on COVID-19 treatments, European Commission, 16 March 2020
2020 ES Espagne Medidas excepcionales aplicables a los ensayos clínicos para gestionar los problemas derivados de la emergencia por COVID-19, AEMPS, Espana, 16 de marzo de 2020
2020 BE Belgique Directive sur la délivrance directe de médicaments aux patients dans le cadre d’essais cliniques, AFMPS, Belgique, 16 mars 2020
2020 NL Pays-Bas Information CCMO due to coronavirus outbreak, CCMO, The Netherlands, March 2020
2020 NL Pays-Bas Recommendations for the conduct of clinical research at the time of restrictive measures due to the coronavirus, CCMO, The Netherlands, March 2020
2020 UK Royaume-Uni Advice for Management of Clinical trials in relation to Coronavirus, MHRA, United Kingdom, 12 March 2020
2020 IT Italie Notice – Clinical trials’ management in Italy during the COVID-19 (coronavirus disease 19) emergency, AIFA, Italia, 12 march 2020
2020 IT Italie Guidance on submission of Marketing Authorization/Extension, MA Variation and Renewal applications, up to the end of the restrictions related to COVID-19 emergency, AIFA, Italia, 12 march 2020
2020 UK Royaume-Uni Research in a public health emergency, MHRA, United Kingdom, 8 March 2020

Délivrance du médicament / produit de santé

La livraison au domicile du patient est possible sous certaines conditions

fr L’ANSM accepte la livraison à domicile du traitement expérimental sous réserve de prise de Mesures Urgentes de Sécurité (MUS), puis de soumission d’une Modification Substantielle (MSA)

fr France « La délivrance à domicile des traitements expérimentaux est-elle autorisée ? Oui dans le respect des consignes de sécurité, de l’information du patient et de la traçabilité.

  • MUS puis MSA précisant les conditions de délivrance (voir ci-dessous), de suivi et d’information des participants

En cas de délivrance à domicile, quel est le circuit préconisé ? La délivrance des produits expérimentaux au patient reste sous la responsabilité de l’investigateur et, si le lieu de recherche en dispose, de la pharmacie à usage intérieur.
Mise en place par le promoteur pour les PUI de lieux de recherche d’une offre de prestation à la charge du promoteur :

  • Le promoteur fournit les emballages et les étiquetages
  • Il vérifie les conditions de transport garantissant la bonne conservation du produit, la sécurité et un acheminement dans un délai adapté,
  • Il s’assure que la PUI dispose des informations relatives au patient pour lui expédier le traitement (adresse de résidence)
  • La traçabilité notamment de l’acheminement et de la réception, doit être assurée et transmise par le transporteur à la PUI assurant la dispensation

Il relève de la responsabilité du promoteur de s’assurer que, dans le contexte de crise sanitaire, le transporteur qu’il a sélectionné apporte toutes les garanties nécessaires à la traçabilité et au respect du délai d’acheminement. » (FAQ – Covid 19 – Essais cliniques en cours, ANSM, France, 20 mars 2020)

fr France « Is delivery of investigational products to the patient’s home allowed? Yes in compliance with safety instructions, patient information and traceability.

  • USM then SM-A specifying the conditions for delivery (see below), monitoring and information of participants

In case of delivery to the patient’s home, what are the requirements? The delivery of investigational products to the patient remains under the responsibility of the investigator and, if available at the research site, of the site’s pharmacy. Implementation by the sponsor for the trial site/pharmacy of a specialised delivery service solution, to be paid for by the sponsor:

  • The sponsor should provide packaging and labelling material,
  • The sponsor should determine the transport conditions guaranteeing the good storage of the product, safety and an appropriate delivery time,
  • The sponsor should ensure that the trial site has the patient’s information in order to send the treatment (home address),
  • The traceability, in particular of routing and receipt, must be ensured and transmitted by the delivery service to the trial site/pharmacy ensuring the dispensing.

It is the sponsor’s responsibility to ensure that, in the context of a health crisis, the transporter it has selected provides all the necessary guarantees for traceability and compliance with delivery times. » (QnA – Covid 19 – Ongoing clinical, ANSM, France, 20 March 2020)

eu L’EMA accepte la livraison du produit expérimental au patient si cela ne compromet pas l’insu et respecte les normes relatives au transport

eu « In line with the reduction of physical site visits, we foresee that there will be a need for delivery of the IMP directly to trial participants during the COVID-19 pandemic to avoid that the trial participant has to reach the site with the consequent risk of spreading/acquiring infection. The delivery is generally expected to happen from investigator sites (e.g. via hospital (or other) pharmacies as applicable) to trial participants; Direct from sponsor to trial participant IMP delivery is accepted in a few member states under this emergency situation. The sponsor should check the NCA guidance regarding the possibility of direct sponsor to trial participant shipment, as it is likely that such measures can only be implemented under specified conditions (e.g. agreement with sites, dedicated couriers with procedures to only allow delivery directly to a trial participant or his/her carer, solid shipment and receipt procedures, informed consent provisions if necessary for the sponsor’s third party to handle personal information etc.), and for a limited period. Alternative shipping and storage arrangements should not compromise the treatment blinding. » (Guidance on the Management of Clinical Trials during the COVID-19 (Coronavirus) pandemic, EMA, 20 March 2020)

BE L’Autorité Compétente belge autorise l’envoi de médicaments expérimentaux au domicile du patient dans des conditions garantissant la confidentalité de la recherche, l’intégrité et la traçabilité des produits envoyés

BE Belgique « Si un patient ne peut pas accéder à l’hôpital, ou si cela n’est pas souhaitable dans le contexte actuel, il est permis d’envoyer des médicaments expérimentaux (Investigational Medicinal Products, IMP) directement au patient. Cela relève de la responsabilité du chercheur principal. Le promoteur d’un essai clinique ne peut intervenir dans ce processus pour des raisons de confidentialité et d’intégrité. Bien entendu, les conditions d’expédition appropriées doivent être respectées. Ce processus doit être documenté et entièrement traçable. » (Directive sur la délivrance directe de médicaments aux patients dans le cadre d’essais cliniques, AFMPS, Belgique, 16 mars 2020 )

UK Au Royaume-Uni, les mesures temporaires mises en place pour l’envoi à domicile ou la récupération du traitment par une personne désignée, doivent être traitées comme des Modifications Non Substantielles (MNS)

UK Royaume-Uni  » 3.1.3. Studies where treatment or investigational medicinal product need to be sent by courier direct to participants or other alternative mechanisms of provision Sponsors must assess the risks relating to the product and consider any shipping and storage arrangements. Participants must consent verbally to providing contact details for shipping purposes. Where participants are self-isolating or in quarantine, arrangements for a nominated person to collect product may be implemented with the participant’s verbal consent. Any such temporary arrangements should be handled as a non-substantial amendment that does not require HRA/HCRW Approval or R&D agreement. For studies involving the NHS/HSC, these should be marked by the sponsor as category C and not requiring assessment and sent directly to sites following the instructions above. These should be implemented at sites on the date specified by the sponsor. » (COVID-19: Guidance for sponsors, sites and researchers V2, MHRA, United Kingdom, 17 March 2020 )

ES En Espagne, l’envoi à domicile ou la réception par une personne autorisée sont possibles durant les mesures prises pour lutter contre le Covid-19 sous réserve que le Promoteur et la PUI puissent s’assurer de la bonne réception et de la bonne administration du traitement au patient

ES Espagne « 3. Acceso al tratamiento del ensayo Los Servicios de Farmacia de los hospitales podrán tomar las medidas que consideren necesarias, por ejemplo, la dispensación a una persona autorizada por el paciente del ensayo de un tratamiento que deba tomarse en casa o el envío desde el Servicio de Farmacia del tratamiento al domicilio del paciente cuando sus circunstancias lo hagan aconsejable. En relación con esto último, deberá asegurarse la conservación del tratamiento durante el transporte y la comunicación con el paciente que permita la recepción y adecuada administración del mismo. Se tendrá en cuenta la sección 10 del documento “Q&A: Good clinicalpractice (GCP)” – GCP Matters”. Deberá valorarse la situación en cada caso particular, por parte del promotor, el investigador principal y el Servicio de Farmacia. » (Medidas excepcionales aplicables a los ensayos clínicos para gestionar los problemas derivados de la emergencia por COVID-19, AEMPS, Espana, 16 de marzo de 2020 )

NL Aux Pays-Bas, l’envoi du traitement à domicile ne doit pas faire l’objet d’une information du Review Commitee mais la procédure doit être enregistrée par écrit

NL Pays-Bas « Study medication can be sent directly to the research subject by courier from the (hospital) pharmacy for reasons of subject safety; you need not inform the review committee about this, but do record this temporary procedure in writing » (Recommendations for the conduct of clinical research at the time of restrictive measures due to the coronavirus, CCMO, The Netherlands, March 2020 )

Possibilité, lors des visites programmées, de fournir au patient le traitement pour une durée plus longue qu’initialement prévu

fr France « La délivrance des traitements expérimentaux pour des durées supérieures est-elle autorisée ? Oui dans le respect des consignes de sécurité, de l’information du patient et de la traçabilité. En cas de suppression des visites lors desquelles les médicaments ou dispositifs expérimentaux auraient dû être délivrés aux patients, des dispositions doivent être prévues afin d’évaluer la tolérance au traitement et d’adapter celui-ci si nécessaire, par exemple par téléconsultation;

  • Soumission à l’ANSM d’une MSI incluant des mesures additionnelles sur le suivi.

Attention : les produits stupéfiants sont exclus de cette mesure.«  (FAQ – Covid 19 – Essais cliniques en cours, ANSM, France, 20 mars 2020)

fr France « Is the delivery of investigational products for longer durations allowed? Yes in compliance with safety instructions, patient information and traceability. If visits during which the investigational medicinal products or devices should have been delivered to patients are skipped, arrangements must be made to assess the tolerability of the treatment and to adjust the treatment if necessary, for example by teleconsultation.

  • Submission to ANSM of a SM-I including additional measures on follow-up.

Caution : narcotic products are excluded from this measure. » (QnA – Covid 19 – Ongoing clinical, ANSM, France, 20 March 2020)

ES Espagne « 3. Acceso al tratamiento del ensayo Se debe garantizar el acceso de los pacientes a la medicación del ensayo en las mismas condiciones en las que se estaba dando. Se recomienda que el investigador valore la posibilidad y conveniencia de que, cuando el paciente acuda a una visita programada reciba una cantidad de medicamento que permita cubrir un periodo mayor de tratamiento. Los Servicios de Farmacia de los hospitales podrán tomar las medidas que consideren necesarias, por ejemplo, la dispensación a una persona autorizada por el paciente del ensayo de un tratamiento que deba tomarse en casa o el envío desde el Servicio de Farmacia del tratamiento al domicilio del paciente cuando sus circunstancias lo hagan aconsejable. En relación con esto último, deberá asegurarse la conservación del tratamiento durante el transporte y la comunicación con el paciente que permita la recepción y adecuada administración del mismo. Se tendrá en cuenta la sección 10 del documento “Q&A: Good clinical practice (GCP)” – GCP Matters”. Deberá valorarse la situación en cada caso particular, por parte del promotor, el investigador principal y el Servicio de Farmacia. » (Medidas excepcionales aplicables a los ensayos clínicos para gestionar los problemas derivados de la emergencia por COVID-19, AEMPS, Espana, 16 de marzo de 2020 )

IT Italie « 1. Investigational medicinal product (IMP) management If possible, when the patient goes to the study site for a visit, it may be useful to provide an amount of medicinal product covering a longer period of time than is normally estimated.
According to current legislation (article 7 of the Ministerial Decree 21st December 2007), the Sponsors must send investigational drugs needed for the trial to the pharmacy of the investigational site, that is in charge for their registration, appropriate storage and delivery to the investigator. Therefore, considering the COVID-19 serious emergency, even if the priority mode remains the delivery to the hospital pharmacy that then proceeds to the subsequent delivery to the investigational centre, direct deliveries from the hospital pharmacy to the trial subjects also through dedicated couriers can be arranged, upon indications of both the hospital pharmacy Director and the Principal Investigator (PI). It is intended that the hospital pharmacy is responsible for the process supervision; the pharmacy and the PI must be constantly informed on the delivery, according to procedures established for the correct conduction of the trial and by the above-said risk plan, that must take into account the IMP typology, administration methods, conservation and transport. Adequate remote communication ways with involved subjects must be implemented to replace the information that will no longer be provided in person. Depending on the case, telephone and/or video call can be used to inform the patient, where deemed necessary. Adequate tracking of what is being implemented in this emergency situation is recommended. All this without prejudice, if possible, to conditions set out in FAQ 10 of the EMA Document “Q&A: Good clinicalpractice (GCP)” – GCP Matters (https://www.ema.europa.eu/en/human-regulatory/research-development/compliance/good-clinical-practice/qa-good-clinical-practice-gcp). If the CRA of the study is not able to carry out the control on the final accounting of the investigational medicinal product for the purpose of reconciliation, and this operation is considered as impossible to be postponed, it can be carried out by a pharmacist of the hospital pharmacy or by the study coordinator/data manager, appropriately trained. The IMP can be returned to the Sponsor directly by the hospital pharmacy. »
(Notice – Clinical trials’ management in Italy during the COVID-19 (coronavirus disease 19) emergency, AIFA, Italia, 12 march 2020 )

Possibilité de redistribuer les médicaments expérimentaux entre différents sites

eu « In case of urgent shortage of IMP at some sites or transfer of trial participants from one site to another clinical trial site, there might be a need to potentially re-distribute the IMP between sites in accordance with GMP annex 13 (section 47). This should only be considered in cases where a direct distribution of the IMP to a trial site by the usual distributor is not possible or in the exceptional circumstance where a trial participant is transferred from one site to another. Sponsors should assess whether sites can handle and control such a re-distribution process, especially in case of restricted conditions for storage such as the need for specific conditions other than room temperature (e.g. +2-8° C). Re-distribution should follow a written procedure established in cooperation with the Qualified Person or the person responsible for distribution of the IMP, and sites should be provided with sufficient information to ensure that the process can be performed securely. Associated records should be included in the transfer » (Guidance on the Management of Clinical Trials during the COVID-19 (Coronavirus) pandemic, EMA, 20 March 2020)

BG Bulgarie « 6. Il est recommandé de maintenir les médicaments et les dispositifs médicaux des essais cliniques en quantité appropriée pour assurer la continuité du traitement en cas de difficulté de livraison. Dans des cas exceptionnels, en cas de pénurie, une redistribution des quantités entre centres agréés est autorisée. Le promoteur doit s’assurer que les conditions de stockage et la sécurité de l’approvisionnement sont maintenues, en suivant une procédure écrite et une documentation bien établies à chaque étape du processus. Ces actions nécessitent une notification à la BDA. » (Traduction des Recommandations aux commanditaires concernant la conduite des essais cliniques dans le cadre du risque complexe de Covid-19 d’une déclaration de l’état d’urgence dans le pays, Version Bulgare )

Procédures accélérées

Procédure accélérée d’examen des demandes d’amendements nécessités par l’épidémie de Covid-19

DE En Allemagne, les demandes d’amendements consécutives à la situation pandémique sont prioritaires

DE Allemagne Les demandes d’amendements consécutives à la situation pandémique seront considérées comme prioritaires (une référence « COVID-19 » est requise en objet). (« Genehmigungsverfahren », BfARM Internet site, Germany, 19 März 2020)

BG En Bulgarie, les demandes de modifications substantielles sont prioritaires

BG Bulgarie « 3. Le promoteur, en collaboration avec le chercheur principal, devrait déterminer si les visites physiques (visites sur place dans les centres) peuvent être transformées en suivi à distance, appels téléphoniques, différés ou annulés entièrement en appliquant l’approche basée sur les risques, les capacités du protocole de test ou son amendement visant à garantir que seules les visites nécessaires soient effectuées dans les centres. En cas de modification substantielle du protocole, dans ces cas, accompagné de la documentation pertinente, il sera considéré comme prioritaire. 4. En l’absence d’alternative, le transfert des participants d’un centre à un autre – un centre nouveau / déjà approuvé dans le règlement est possible en cas d’urgence. Dans de tels cas, il est important de s’assurer que les patients sont traités en continu. Les participants au test et les deux chercheurs principaux doivent s’entendre sur la relocalisation, et le centre d’accueil devrait avoir un accès rapide aux informations – données collectées auprès des participants au test. Si une ou des demandes de modification substantielle sont nécessaires dans ces cas-là, elles devront être accompagnées d’une documentation pertinente, et leur examen sera priorisé.«  (Traduction des Recommandations aux commanditaires concernant la conduite des essais cliniques dans le cadre du risque complexe de Covid-19 d’une déclaration de l’état d’urgence dans le pays, Version Bulgare )

Procédure accélérée d’examen des essais relatifs au Covid-19

fr En France, mise en place d’une procédure dérogatoire au tirage au sort des CPP et l’évaluation initatiale des demandes d’autorisations

fr France « Modalités d’évaluation des essais cliniques en lien avec la prise en charge de la pandémie COVID-19 Des procédures accélérées pour l’évaluation initiale des demandes d’autorisations ont été mises en place par l’ANSM, la DGS et l’ensemble des CPP. Afin de garantir le bon suivi de ces dossiers, il convient de prendre contact avec l’ANSM et la DGS afin de prioriser l’essai clinique, d’orienter l’évaluation et d’établir si des informations additionnelles sont nécessaires. Un contact avec la DGOS sera utile avant finalisation de la procédure d’autorisation initiale afin d’anticiper l’ouverture des centres : DGOS-PF4@sante.gouv.fr Comme demandé à l’Organisation Mondiale de la Santé, le promoteur doit veiller inclure dans le titre de la recherche la mention de l’acronyme officiel de l’infection par SARS-CoV-2 (COVID-19). De même, pour toute soumission, il est demandé de mentionner COVID-19 dans l’objet du mail. Les équipes développant des médicaments ou des vaccins sont invitées à contacter l’EMA dès que possible pour partager des informations sur leur projet en envoyant un courriel à 2019-ncov@ema.europa.eu. L’EMA offre une dispense de frais et une procédure accélérée pour les avis scientifiques . » (FAQ – Covid 19 – Essais cliniques en cours, ANSM, France, 20 mars 2020)

fr France « Modalities for the evaluation of clinical trials related to the management of the pandemic COVID-19 Accelerated procedures for the initial assessment of applications for authorisation have been put in place by ANSM, DGS and all ECs. In order to ensure the proper follow-up of these dossiers, contact should be made in order to prioritise the clinical trial, guide the evaluation and determine whether additional information is needed. Contact with Ministery of Health (DGOS) is also useful before finalisation of the initial authorisation procedure in order to anticipate the opening of the centers : DGOS-PF4@sante.gouv.fr It should be noted that the developers of medicines or vaccines are invited to contact EMA as soon as possible with information about their proposed development by emailing 2019-ncov@ema.europa.eu . EMA provides a full fee waiver and a fast-track procedure for scientific advice. As requested by the WHO, sponsor must ensure that the WHO official acronym for the coronavirus disease (COVID-19) is entered in the title field of the trial registration data set. » (QnA – Covid 19 – Ongoing clinical, ANSM, France, 20 March 2020)

eu En Europe, les Promoteurs sont encouragés à utiliser l’évaluation rapide de la Voluntary Harmonisation Procedure (VHP)

eu « The Member States support the submission of large, multinational trial protocols for the investigation of new treatments for COVID19. In addition, sponsors are encouraged to consider the submission of such applications for an accelerated Voluntary Harmonisation Procedure (VHP) assessment when possible. In order to avoid or minimise delays due to the harmonised review, sponsors are recommended to prospectively contact the proposed Ref NCA to explore the feasibility of an accelerated VHP (plus) process. It should be noted that the developers of medicines or vaccines are invited to contact EMA as soon as possible with information about their proposed development by emailing 2019-ncov@ema.europa.eu. EMA provides a full fee waiver and a fast-track procedure for scientific advice. »(Guidance on the Management of Clinical Trials during the COVID-19 (Coronavirus) pandemic, EMA, 20 March 2020)

IT En Italie, une procédure accélérée est mise en place pour les demandes de renouvellement et d’extention d’Autorisations de Mise sur le Marché (AMM)

IT Italie « Please be informed that, due to COVID-19 emergency and the difficulties that some MA holders are facing, as exception to the provisions given in the guidance published the 7th May 2019, the Marketing Authorizations Department will accept:

  1. 1. the submission of MA variation and renewal applications/noifications through the relevant portals; the submission of what required in the above mentioned guidance can be postponed
  2. 2. the submission through CESP of MA/extension applications (N,MR,DC); the submission of what required in the above mentioned guidance can be postponed
    The provisions given above are also applicable to responses/additional documents

The provisions given above are also applicable to responses/additional documents » (Guidance on submission of Marketing Authorization/Extension, MA Variation and Renewal applications, up to the end of the restrictions related to COVID-19 emergency, AIFA, Italia, 12 march 2020)

DK Au Danemark, les projets de recherche clinique portant sur le Covid-19 seront étudiés sous 3 jours

DK Danemark « Clinical trials investigating treatments for COVID-19 will be processed within 3 days. The processing time is extended if major objections is raised but we prioritise to have these solved immediately. (…) We prioritise all inquiries about COVID-19 (please clearly mark the topic ‘COVID-19’) at . We can also be contacted by phone (4488 9123). » Fast-track Approval of Clinical Trials investigating COVID-19, Danish Medicines Agency, Denmark, 17 March 2020)

NL Aux Pays-Bas, une procédure accélérée est mise en place pour les recherches portant sur le développement de vaccins contre le Covid-19

NL Pays-Bas « Accelerated procedure (fast track) assessment of coronavirus research files Given the current developments around the outbreak of the new coronavirus (COVID-19), CCMO facilitates an accelerated assessment of research files on the development of vaccines against this coronavirus (fast-track procedure). If you would like to make use of this fast-track procedure, please contact CCMO via ccmo@ccmo.nl or telephone number 070 340 6700. CCMO will then determine whether your research qualifies for the fast-track procedure. The fast-track procedure means that the time at which the assessment normally starts can be brought forward and the procedure is handled by a subcommittee mandated by CCMO. For a fast-track assessment by the competent authority, please send a message to bi@ccmo.nl stating FAST TRACK COVID-19. » (Information CCMO due to coronavirus outbreak, CCMO, The Netherlands, March 2020 )

ES En Espagne, l’évaluation des essais cliniques visant à traiter ou prévenir les coronavirus est priorisée

ES Espagne « 6. Ensayos clínicos dirigidos a la investigación de nuevos medicamentos frente al coronavirus La AEMPS está priorizando junto con los CEIm la evaluación de los ensayos clínicos destinados a tratar o prevenir la enfermedad por coronavirus. Los promotores o investigadores que tengan un proyecto de investigación de este tipo deben enviar un mensaje a Área de Ensayos Clínicos indicando en el asunto: URGENTE nuevo EC COVID19. Se dará una respuesta el mismo día. » (Medidas excepcionales aplicables a los ensayos clínicos para gestionar los problemas derivados de la emergencia por COVID-19, AEMPS, Espana, 16 de marzo de 2020 )

UK Le Royaume-Uni a mis en place une procédure d’examen accélérée pour les recherches sur le Covid-19 présentant un intérêt de santé publique

UK Royaume-Uni « An expedited review process is available for studies relating to COVID-19 where there are public health grounds for rapid review. The full process for fast-track reviews is set out in the Standard Operating Procedures for Research Ethics Committees. Researchers should contact the HRA Director of the Approvals Service (who will liaise with colleagues in Scotland, Wales or Northern Ireland if applicable), copying in their research sponsor, as early as possible to request expedited review. » (COVID-19: Guidance for sponsors, sites and researchers V2, MHRA, United Kingdom, 17 March 2020)

Conduite de la recherche

Le Promoteur doit envisager la suspension ou l’arrêt d’une recherche en cours si la poursuite de la recherche entrainait la mise en danger des participants

FR France « Un essai peut-il être suspendu en raison de la pandémie ?
Oui
Une décision de suspension des inclusions peut être justifiée par le contexte de l’étude et/ou l’indisponibilité des équipes (sponsor ou investigateurs).
La poursuite ou non des traitements en cours doit être précisée et justifiée. Une décision d’arrêt des traitements en cours doit en effet être impérativement évaluée en fonction du contexte clinique de chaque patient et des risques alors encourus.

FR France« May a trial be suspended because of the pandemic? Yes A decision to suspend inclusions may be justified by the context of the study and/or the unavailability of teams (sponsor or investigators). The continuation or not of ongoing treatments must be specified and justified. A decision to discontinue ongoing treatments must be evaluated according to the clinical context of each patient and associated risks.

eu « The sponsors should consider in their risk assessment whether the following measures could be the most appropriate during COVID-19. Measures should generally be agreed with investigators and could be: (…)

NL Pays-Bas « If the trial is (partially) suspended, this must be reported immediately to the review committee; If the study is terminated prematurely, this must be reported to the review committee as soon as possible, but at the latest within 15 days; » (Recommendations for the conduct of clinical research at the time of restrictive measures due to the coronavirus, CCMO, The Netherlands, March 2020)

UK Royaume-Uni « 3.1.4. Studies where sponsors need to implement a temporary halt to all or some of the study or extend the duration of a study due to COVID-19.
Sponsors must decide when they need to implement a formal temporary halt. For CTIMPs the MHRA provides advice. For non-CTIMPs consider reporting a formal halt if there are safety considerations for existing participants, or actions that sites need to take. Simply pausing recruitment does not need to be reported as a temporary halt, although sponsors should record such decisions for their records.
For CTIMPs, where MHRA have advised this is a substantial amendment, such amendments will be categorised and assessed according to existing guidance, but the process will be expedited. They should be sent to sites following the instructions above. These should be implemented at sites on the date specified by the sponsor. For non-CTIMPs where a formal halt is required, this should be handled as a non-substantial amendment that does not require HRA/HCRW Approval or R&D agreement. For studies involving the NHS/HSC, these should be marked by the sponsor as category C and not requiring assessment and sent directly to sites following the instructions above. These should be implemented at sites on the date specified by the sponsor.
3.1.5. Studies that need to be closed
For any studies not involving provision of treatment to participants, a notification to the REC or study-wide review (for non-REC studies) should be provided, and an end of study report should subsequently be provided.
For any studies involving provision of treatment to participants, careful consideration should be given to post-study care. If this cannot be in line with the information provided in the participant-information sheet, a substantial amendment should be submitted. Such amendments will be categorised and assessed according to existing guidance, but the process will be expedited. They should be sent to sites following the instructions above. These should be implemented at sites on the date specified by the sponsor. »
(COVID-19: Guidance for sponsors, sites and researchers V2, MHRA, United Kingdom, 17 March 2020)

Le Promoteur doit envisager la fermeture de sites d’investigation, si la sécurité des patients ou la continuité de l’essai ne peuvent être assurées

eu « The sponsors should consider in their risk assessment whether the following measures could be the most appropriate during COVID-19. Measures should generally be agreed with investigators and could be:(…)

BG Bulgarie « 5. Dans le cas où il n’est pas possible pour un centre de poursuivre son implication, le promoteur devrait envisager de fermer le centre et comment cela sera fait pour garantir au mieux la sécurité des patients et la validité des données notifiées. à la BDA. » (Traduction des Recommandations aux commanditaires concernant la conduite des essais cliniques dans le cadre du risque complexe de Covid-19 d’une déclaration de l’état d’urgence dans le pays, Version Bulgare )

IT Italie « 3. Sites closing If a site is closed to the public for COVID-19 containment measures, it should be carefully assessed if the clinical trial staff is able to guarantee the continuity of the trial itself. In case the site is unable to follow the patients undergoing the trial, the study should be temporarily halted or, where possible, enrolled patients should be transferred to the nearest active trial site. Information exchange between PIs must be assured, as well as the transmission of clinical documentation and other trial material (e.g. IMPs) between sites. Contacts between Sponsor and health structures involved must be updated according to new agreements. A site not authorized to participate in the specific clinical trial is not considered as suitable as back-up, since it is not active, it does not know the trial and could not ensure a proper therapeutic continuity for the patient. » (Notice – Clinical trials’ management in Italy during the COVID-19 (coronavirus disease 19) emergency, AIFA, Italia, 12 march 2020 )

Le Promoteur doit évaluer la possiblité de poursuivre ou non le recrutement de patients

eu « The sponsors should consider in their risk assessment whether the following measures could be the most appropriate during COVID-19. Measures should generally be agreed with investigators and could be: (…) Suspension or slowing down of recruitment of new trial participants; » (Guidance on the Management of Clinical Trials during the COVID-19 (Coronavirus) pandemic, EMA, 20 March 2020)

BG Bulgarie « 2. Sur la base de l’évaluation des risques, le promoteur devrait déterminer si le recrutement des participants au test peut être suspendu. » (Traduction des Recommandations aux commanditaires concernant la conduite des essais cliniques dans le cadre du risque complexe de Covid-19 d’une déclaration de l’état d’urgence dans le pays, Version Bulgare )

ES Espagne « 2. Reclutamiento de nuevos pacientes Las desviaciones al protocolo previstas con carácter prospectivo no son aceptables y es esperable que todos los sujetos que se incluyan en un ensayo clínico cumplan todos los criterios de selección. El promotor junto con el investigador, en base a una valoración beneficio/riesgo que considere las características del ensayo y las circunstancias de los centros participantes podrá interrumpir el reclutamiento e incluso interrumpir el tratamiento de los pacientes del ensayo en aras a evitar riesgos innecesarios y garantizar la mejor asistencia sanitaria posible a los pacientes. Este análisis es especialmente pertinente en los ensayos clínicos que conlleven el tratamiento con inmunosupresores y por tanto un riesgo mayor de infección, sin expectativa de beneficio para los participantes. En el caso de una interrupción del ensayo que conlleve la paralización del tratamiento en parte de los pacientes, el promotor tendría que notificar dichas medidas como “medidas urgentes de seguridad” explicando las medidas adoptadas para garantizar el tratamiento alternativo de los pacientes enviando un informe Ad Hoc tanto a la AEMPS como al Comité de Ética de la Investigación con medicamentos. (CEIm) en los 15 días siguientes a la interrupción o finalización. » (Medidas excepcionales aplicables a los ensayos clínicos para gestionar los problemas derivados de la emergencia por COVID-19, AEMPS, Espana, 16 de marzo de 2020 )

UK Royaume-Uni « 3.2.1. Studies where sites need to suspend recruitment Sites must raise such issues with the sponsor as early as possible if this is likely to occur. No further action by sites is required except where instructed by sponsors. It is for the sponsor to decide whether or not to temporarily halt or close a study (see 3.1.4 or 3.1.5 above). » (COVID-19: Guidance for sponsors, sites and researchers V2, MHRA, United Kingdom, 17 March 2020)

Les déviations prospectives au protocole portant sur les critères d’éligibilité ne sont pas plus acceptées

eu « Please note that prospective protocol waivers remain unacceptable and that patients should not be included in trials without proper eligibility assessment, including performance of planned tests, and written informed consent according to national laws and regulations. » (Guidance on the Management of Clinical Trials during the COVID-19 (Coronavirus) pandemic, EMA, 20 March 2020)

eu « We acknowledge that the COVID-19 situation is likely to introduce more protocol deviations than normal. We expect that the sponsor escalates and manages such protocol deviations in accordance with their standard procedures. A proportionate approach will be taken by the GCP inspectors when such deviations are reviewed during inspections, in particular where the best interest of the participant is maintained, and the participant is not put at risk. An increase in protocol deviations in relation to the COVID-19 situation will in itself not trigger the actions required by GCP § 5.20. They will however need to be assessed and reported in the clinical study report, following ICH E3. » (Guidance on the Management of Clinical Trials during the COVID-19 (Coronavirus) pandemic, EMA, 20 March 2020)

UK Royaume-Uni « Prospective protocol waivers remain unacceptable, we would not expect you to bypass the eligibility process due to difficulties in assessing subjects and carrying out tests. Safety of patients of course remains a priority and they should not be included into a trial unless you can confirm they meet the inclusion and exclusion criteria. Similarly, if the safety of a trial subject is at risk because they cannot complete key evaluations or adhere to critical mitigation steps, then consideration to discontinuing that subject must be discussed. This may also extend to the whole trial in some cases, and a Sponsor and Investigator should not forget they are able to use Urgent Safety Measures, or even temporarily halt a trial, or halt recruitment, if this is the best way forward. » (Research in a public health emergency, MHRA, United Kingdom, 8 March 2020 )

Possibilité de transférer en urgence des patients vers un autre centre

fr France « Un patient peut-il changer de lieu de recherche pour décharger un centre en tension ou afin de limiter ses déplacements ? » Oui

fr France « May a patient change his trial site in order to unburden a centre in tension or in order to limit his journeys? Yes

fr France « De nouveaux lieux de recherche (centres investigateurs) peuvent-ils être ouverts rapidement pour décharger des centres en tension ou pour limiter les déplacements des patients en cours de traitement ? Oui

fr France « May new trial sites be opened quickly in order to unburden centers under stress or to limit journeys for patient on treatment? Yes

eu « The sponsors should consider in their risk assessment whether the following measures could be the most appropriate during COVID-19. Measures should generally be agreed with investigators and could be: (…) If unavoidable (it should be justified that this is a truly exceptional situation based on the personal risk-benefit ratio for the individual trial participant), transfer of participants to investigational sites away from risk zones, or closer to their home, to sites already participating in the trial, or new ones could occur. Initiation of new trial sites is generally not expected in the current situation unless no other solution exists for the trial participant. If there is an urgent need to open a new trial site for critical trial visits for example outside the hospital, this may be implemented as an urgent safety measure (USM) first, with a substantial amendment (SA) application submitted later as for the approval and initiation of an additional site later. The exceptional situation could involve e.g. a trial participant who urgently needs to stay in the trial and for whom no other sites are available. In such cases, it is important that trial participants as well as investigators (both receiving and sending) are in agreement about the transfer and that the receiving site has the possibility to access previously collected information/collected data for the trial participant and that any eCRF can be adjusted accordingly to allow the receiving site to enter new data. The impact on trial participants should be considered and arrangements made to e.g. appropriate transportation; transport » (Guidance on the Management of Clinical Trials during the COVID-19 (Coronavirus) pandemic, EMA, 20 March 2020)

BG Bulgarie « 4. En l’absence d’alternative, le transfert des participants d’un centre à un autre – un centre nouveau / déjà approuvé dans le règlement est possible en cas d’urgence. Dans de tels cas, il est important de s’assurer que les patients sont traités en continu. Les participants au test et les deux chercheurs principaux doivent s’entendre sur la relocalisation, et le centre d’accueil devrait avoir un accès rapide aux informations – données collectées auprès des participants au test. Des changements substantiels sont nécessaires dans ces cas, accompagnés d’une documentation pertinente, qui sera priorisée. » (Traduction des Recommandations aux commanditaires concernant la conduite des essais cliniques dans le cadre du risque complexe de Covid-19 d’une déclaration de l’état d’urgence dans le pays, Version Bulgare )

ES Espagne « 5. Transferencia de pacientes de unos centros a otros Si fuera necesario el traslado de un paciente de un centro del ensayo a otro, éste se podrá realizar siempre que: a) se firme un acuerdo de transferencia entre centros, b) el nuevo centro tenga acceso al cuaderno de recogida de datos y a la historia clínica del paciente (o en su defecto el centro original le envíe una copia de la misma); c) el centro original envíe un informe de transferencia que resuma los datos médicos más relevantes del paciente en relación con el ensayo para facilitar su seguimiento al nuevo centro; d) la transferencia del paciente quede documentada en el archivo del ensayo de los dos centros. » (Medidas excepcionales aplicables a los ensayos clínicos para gestionar los problemas derivados de la emergencia por COVID-19, AEMPS, Espana, 16 de marzo de 2020 )

UK Royaume-Uni « 3.2.2. Studies where sites need to move participant visits due to re-allocation of staff and resources to clinical care or limiting participant contact Sites must raise such issues with the sponsor as early as possible if this is likely to occur. Where possible such arrangements should be handled prospectively, and, where required, submitted as an amendment. In cases where there is no time to arrange for such review, changes should be implemented as urgent safety measures and reported retrospectively. In any such situation the impact on participants should be considered and arrangements made to cover this, for example additional transport. Where participant visits can be done remotely rather than face to face this does not need to be reported as an amendment, although it may be appropriate to record this if it might affect the study data, for example subjective interview responses. Where individual sites need to arrange to courier treatment to patients, this does not need to be reported as an amendment, but should be agreed with the sponsor and a risk assessment documented. If patient visits need to be moved, the options are to set up as a sub-contracted site of the existing site if oversight can be maintained by the existing site, or to set up new sites, or to implement direct home care arrangements by the sponsor. For study types where addition of new sites is a substantial amendment, existing guidance for submitting a substantial amendment for new sites should be followed. In all other cases, existing guidance for non-substantial amendments and addition of new sites should be followed. Establishing subsidiary sites is a non-substantial amendment. These should be handled as a non-substantial amendment that does not require HRA/HCRW Approval or R&D agreement. For studies involving the NHS/HSC, these should be marked by the sponsor as category C and not requiring assessment and sent directly to sites following the instructions above. These should be implemented at sites on the date specified by the sponsor. » (COVID-19: Guidance for sponsors, sites and researchers V2, MHRA, United Kingdom, 17 March 2020)

Le Promoteur doit déterminer si les visites des patients doivent être maintenues ou faire l’objet d’aménagement

fr France « Les visites de suivi des patients peuvent-elles être adaptées ? Oui Le recueil d’information par téléconsultation est recommandé à titre exceptionnel, centrée sur les critères de vigilance et le critère principal. Toute donnée non évaluable à distance sera notée manquante. La non réalisation d’une visite protocolaire ne sera pas considérée comme un motif de sortie d’étude et au-delà de la nécessaire documentation, ne sera pas considérée comme une déviation majeure devant être notifiée à l’ANSM selon les BPC § 5.20. Les déviations devront néanmoins être signalées et évaluées dans le rapport final de l’essai (Cf. guideline ICH E3).

fr France « May patient follow-up visits be adapted? Yes The collection of information by teleconsultation is recommended on an exceptional basis, with a focus on safety data and primary objective endpoints. Any data that cannot be assessed remotely will be noted as missing. The failure to complete a protocol visit will not be considered as a reason for study discontinuation and, beyond the necessary documentation, will not be considered as a major deviation that must be notified to the ANSM according to GCP § 5.20. Deviations shall nevertheless be reported and evaluated in the final study report (see ICH guideline E3).

eu « The sponsors should consider in their risk assessment whether the following measures could be the most appropriate during COVID-19. Measures should generally be agreed with investigators and could be: Conversion of physical visits into phone or video visits, postponement or complete cancellation of visits to ensure that only strictly necessary visits are performed at sites; » (Guidance on the Management of Clinical Trials during the COVID-19 (Coronavirus) pandemic, EMA, 20 March 2020)

BG Bulgarie« 3. Le promoteur, en collaboration avec le chercheur principal, devrait déterminer si les visites physiques (visites sur place dans les centres) peuvent être transformées en suivi à distance, appels téléphoniques, différés ou annulés entièrement en appliquant l’approche basée sur les risques, les capacités du protocole de test ou son amendement visant à garantir que seules les visites nécessaires soient effectuées dans les centres. En cas de modification substantielle du procès-verbal, dans ces cas, accompagné de la documentation pertinente, il sera considéré comme prioritaire. » (Traduction des Recommandations aux commanditaires concernant la conduite des essais cliniques dans le cadre du risque complexe de Covid-19 d’une déclaration de l’état d’urgence dans le pays, Version Bulgare )

ES Espagne « 1. Visitas presenciales programadas de los pacientes de un ensayo clínico El promotor junto con el investigador deberá considerar la conveniencia de posponer dichas visitas, o transformarlas en visitas telefónicas, reprogramándolas en el calendario de visitas del ensayo clínico. Deberá garantizarse que las visitas programadas in situ que sean críticas se lleven a cabo. En el caso de reprogramar las visitas estas desviaciones del protocolo no se considerarán incumplimientos graves a menos que pongan en riesgo la seguridad del paciente. » (Medidas excepcionales aplicables a los ensayos clínicos para gestionar los problemas derivados de la emergencia por COVID-19, AEMPS, Espana, 16 de marzo de 2020 )

us Etats-Unis « C. For all trials that are impacted by the COVID-19 pandemic: Sponsors should describe in appropriate sections of the clinical study report (or in a separate study-specific document):

  1. Contingency measures implemented to manage study conduct during disruption of the study as a result of COVID-19 control measures.
  2. A listing of all participants affected by the COVID-19 related study disruption by unique subject number identifier and by investigational site, and a description of how the individual’s participation was altered.
  3. 3Analyses and corresponding discussions that address the impact of implemented contingency measures (e.g., trial participant discontinuation from investigational product and/or study, alternative procedures used to collect critical safety and/or efficacy data) on the safety and efficacy results reported for the study.

Robust efforts by sponsors, investigators, and IRBs/IECs to maintain the safety of trial participants and study data integrity are expected, and such efforts should be documented. As stated above, FDA recognizes that protocol modifications may be required, including unavoidable protocol deviations due to COVID-19 illness and/or COVID-19 control measures. Efforts to minimize impacts on trial integrity, and to document the reasons for protocol deviations, will be important. »(Coronavirus (COVID-19) Update: FDA Issues Guidance for Conducting Clinical Trials, FDA, USA, 18 March 2020)

Modalités spécifiques de recueil du consentement

eu « Sponsors should be mindful of the current pressure on the medical profession and should carefully assess the pertinence of adding new subjects in ongoing clinical trials. Absolute priority should be given to clinical trials on treatments for COVID-19 and COVID19-COVID-19related illnesses, or trials on serious diseases with no satisfactory treatment option. In case a sponsor plans to initiate a trial aiming to test new treatments for COVID-19, advice should be sought on alternative procedures to obtain informed consent, as it is likely that the physical consent cannot leave the isolation room, and therefore is not appropriate as trial documentation. In case of emergency situations, when trial participants are incapable of giving their informed consent (for example because they are under intensive medical care), sponsors shall adhere to the provisions set out in the Directive (Art 5) and by national regulations. Informed consent of these patients or their representatives will need to be acquired later, as soon as feasible, if deferred consent in emergency situations is permitted under national law. There may be a need to re-consent already included trial participants. However, avoid the need for trial participants to visit investigator sites for the sole purpose of obtaining re-consent. If re-consents are necessary for the implementation of new urgent changes in trial conduct (mainly expected for reasons related to COVID-19), alternative ways of obtaining such re-consents should be considered during the pandemic e.g. contacting the trial participants via phone or video-calls and obtaining oral consents supplemented with email confirmation. Any consent obtained this way should be documented and confirmed by way of normal consent procedures at the earliest opportunity when the trial participants will be back at the regular sites Any validated and secure electronic system already used in the trial for obtaining informed consent can be used as per usual practice and if in compliance with national legislation. » (Guidance on the Management of Clinical Trials during the COVID-19 (Coronavirus) pandemic, EMA, 20 March 2020)

Le Plan de Monitoring doit être adapté et actualisé (possibilité de visites de monitoring, révision des procédures…)

fr France « Les visites de monitoring sont-elles possibles dans les lieux de recherche ?

  • Les consignes de confinement actuellement en place doivent être respectées. Il convient de considérer un report des visites sur site selon les recommandations nationales et contraintes locales.
  • Le promoteur est incité à contacter les investigateurs afin de s’adapter aux contraintes de chaque lieu de recherche.
  • Le monitoring centralisé reste possible avec contact promoteur / centre sous réserve de la disponibilité des équipes investigatrices en situation de tension. L’envoi de copies des dossiers médicaux, même pseudonymisés, n’est pas autorisé.

fr France « Are monitoring visits to trial sites possible?

  • Existing containment guidelines must be followed. Postponement of site visits should be considered according to national recommendations and local constraints.
  • The sponsor is encouraged to contact the investigators in order to adapt to the constraints of each trial site.
  • Centralised monitoring remains possible with sponsor/site contact subject to the availability of the research teams in tense situations. Sending copies of medical records, even pseudonymised, is not authorised.

eu « Certain sponsor oversight responsibilities, such as monitoring and quality assurance activities need to be re-assessed and temporary, alternative proportionate mechanisms of oversight may be required. The extent of on-site monitoring, if it remains feasible, should take into account national and local restrictions, the urgency (e.g. source data verification can often be postponed) and the availability of site staff, and should only be performed as agreed with investigator sites. The burden of the introduction of any alternative measures for the site staff and facilities should also be considered in order to strike an acceptable balance between appropriate oversight and the capacity of and possibilities at the site. Possible temporary, alternative measures could include:

  • Cancelling of on-site monitoring visits and extending of the period between monitoring visit;
  • Implementing phone and video visits (without unnecessarily increased burden to the investigator site and taking into account trial participant integrity);
  • Adapting the on-site monitoring plan when it is impossible to follow, supplementing it with (additional/increased) centralised monitoring and central review of data if possible and meaningful.

Results of adjusted monitoring/review measures should be reported to the sponsor in monitoring reports and in the clinical study report. It is essential that robust follow-up measures are planned and ready to be implemented when the situation is normalised. This should likely include increased on-site monitoring for a period that is sufficient to ensure that the impact of the reduced monitoring could be rectified and problems resolved or properly documented for reporting in the clinical study report. So-called remote source data verification (e.g. providing sponsor with copies of medical records or remote access to electronic medical records) is currently not allowed in most member states as it might infringe trial participants’ rights. In addition, provision of redacted/ de-identified pdfs files will not be acceptable as it puts disproportionate burden on site staff. Nevertheless, since the coronavirus emergency situation and containment measures are likely to last for a prolonged period, several NCAs have started to look into possible, temporary solutions related to remote access and conditions for such, providing that methods can be used that restricts access to trial participant records, in line with the principles of necessity and proportionality. This should however also be clarified with other relevant authorities in this area (such as, without limitation, Ethics Committees and data protection agencies) and is consequently not allowed unless a member state has given specific guidance allowing this. » (Guidance on the Management of Clinical Trials during the COVID-19 (Coronavirus) pandemic, EMA, 20 March 2020)

BG Bulgarie « En ce qui concerne le suivi des essais, il est recommandé que le plan de suivi soit suivi des procédures du promoteur etdes options pour diluer les visites de suivi ou les faire à distance conformément aux règles de bonnes pratiques cliniques. Les modifications du plan de surveillance ne sont pas soumises à la déclaration de la BDA. » (Traduction des Recommandations aux commanditaires concernant la conduite des essais cliniques dans le cadre du risque complexe de Covid-19 d’une déclaration de l’état d’urgence dans le pays, Version Bulgare )

ES Espagne « 4. Visitas de monitorización Se recomienda al promotor actualizar los planes de monitorización del ensayo para los cuatro próximos meses priorizando la monitorización centralizada y la monitorización remota de los centros participantes que no conlleve sobrecargar de tareas al personal del centro ni la revisión de datos fuente y posponiendo en la medida de lo posible la verificación de datos fuente hasta poder acceder a la historia médica de forma presencial. El promotor acordará con los centros y equipos participantes las condiciones para dichas monitorizaciones. » (Medidas excepcionales aplicables a los ensayos clínicos para gestionar los problemas derivados de la emergencia por COVID-19, AEMPS, Espana, 16 de marzo de 2020 )

IT [Italie] « 4. Clinical trial monitoring By analogy with what stated in the previous paragraph, Sponsors are invited to draw up a risk evalutation plan and implement an action plan taking into account the need to reduce unnecessary contacts in this period of COVID-19 epidemiological emergency. First of all, it should be assessed whether in-situ monitoring visits can be replaced by an enhanced centralised monitoring or whether such local visits can be postponed. Exceptional methods such as telephone contacts or, even better, videoconferences with the trial site staff can be implemented for the purpose of source data verification. These methods must be described in a specific SOP by the Sponsor/CRO and must be evaluated and approved by the Personal Data Protection Officer of the trial site. Other unusual monitoring methods involving more risky ways of accessing sensitive data, such as video recording of source document or making available to monitors original documents in shared electronic areas, must always be agreed with the Personal Data Protection Officer of the hospital, but it is considered appropriate that a specific opinion by the Italian Data Protection Authority be obtained. » (Notice – Clinical trials’ management in Italy during the COVID-19 (coronavirus disease 19) emergency, AIFA, Italia, 12 march 2020 )

L’investigateur doit évaluer la pertinence de poursuivre le traitement expérimental si un patient inclus dans l’essai est diagnostiqué positif au Covid-19

fr France « Quelle attitude en cas de diagnostic d’infection COVID-19 chez un patient inclus dans un essai et en cours de traitement expérimental ? La poursuite ou la suspension des traitements expérimentaux doit être évaluée par l’investigateur en lien avec le promoteur en fonction du contexte clinique. Les modalités de dépistage des patients en cours d’essai thérapeutique doivent être alignées sur les recommandations nationales.

fr France « What should be done if a patient included in a trial and under treatment becomes infected with SARS-CoV-2? The continuation or suspension of investigational products should be evaluated by the investigator in liaison with the sponsor based on the clinical context. Testing strategy for clinical trials patients have to be in line with national recommendations.

Inspections

Possibilité d’inspection par voie électronique

UK Royaume-Uni « On 20th March 2020 MHRA announced a risk-based prioritisation of Good Practice inspections due to the COVID19 outbreak. Until further notice, MHRA will only conduct on-site inspections linked to the UK Government’s COVID19 response or any other potential serious public health risk, and where remote assessment is not possible. Other inspections will be temporarily replaced with alternative regulatory supervision approaches such as office-based assessment. This will support the industry and NHS to focus on service continuity, and essential clinical trial authorisation applications will not be affected. During this period of disruption, MHRA’s remote assessment procedures and our communication with the international regulatory network will maintain protection of public health.

  • Office based inspections will involve organisations being asked to provide electronic copies of documents and other information for review off-site, with teleconferences and email to follow up. Where necessary, the on-site portion of routine surveillance such as manufacturing plant tours and oversight of clinical trials facilities will be re-scheduled when travel restrictions are lifted
  • Our confidentiality arrangements with the 53 global inspectorates in the Pharmaceutical Inspection Cooperation Scheme (PIC/S), mutual recognition partners and other collaborating regulators ensures that we have access to GxP information on international organisations and supply chains involved in the development, manufacture and supply of medicines. The PIC/S Inspection reliance procedure is particularly important, as it sets out a framework for participating authorities to rely on the inspection information provided by the network.

If on-site inspection is required, we will continue to operate to normal procedures, including the possibility of an unannounced visit if considered necessary to protect public health. Our inspectors will take all possible steps to protect the inspected organisation and themselves from COVID19 transmission risks, including strict hygiene measures in line with UK Government advice » (MHRA Good Practice (GxP) inspections during the COVID19 outbreak, MHRA, Great-Britain, 23 March 2020)