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Early dialogue (ED) for a medicinal product in clinical development

Best practice guidance for pharmaceutical companies for submission and proceeding of an early dialogue at the national level (with HAS) or at the European level (with EMA and/or other HTA bodies)

Date of validation
March 2016

 

Sections

 

1.  Objective

The L161-37 article of the social security code gives to HAS the mission of early dialogues (ED) organisation.

The objective of an ED for a medicinal product in clinical development is to provide scientific recommendations to pharmaceutical companies on how the last phase (usually phase III) of development of a drug should be conducted in order to enable the company to provide data that will satisfy the requirements of the health technology assessment (HTA).

An ED does not constitute an assessment. Furthermore, they do not preclude the conclusions of the assessment at the time of the file submission, whether that of the Transparency Committee (TC) or, where applicable, that of the Economic and Public Health Evaluation Committee (CEESP).

For that purpose, HAS, as other HTA bodies and EMA[1], answer questions raised by the company about the way it is going to conduct the last phase (usually, phase III) of the development of a drug. These responses are based on the health technology assessment methods and on the relevant international guidelines in accordance with national requirements.



[1] This guidance should be read in conjunction with Best Practice guidance for the EMA Parallel Regulatory HTA scientific Advice procedure

 



 

2.  General considerations

The ED are optional, free of charge, non-binding for HAS and the companies, and confidential between the company, HAS, the other HTA bodies and EMA.

EDs can be conducted in English.

 

3.  Methods

The general process includes the following steps:

  • Request
  • Admissibility
  • Analysis of the dossier
  • List of Questions asked by the company
  • Preparation of the answers
  • Face-to-Face meeting
  • Report of the meeting
  • Validation of the report

The ED documents are sent to the Medicines Assessment Department to the following address:

Emmanuelle Cohn/Anne d’Andon
Medicines Assessment Department
Haute Autorité de santé
5 avenue du Stade de France
93218 Saint-Denis La Plaine Cedex
 e.cohn[a]has-sante.fr and a.dandon[a]has-sante.fr

 

 

TABLE 1: general overview with the different steps of an ED

Steps

Who?

How?

When?

Request and Briefing book version 1

(BB1)

Company

Provide information on how the drug fulfills the criteria for an ED, proposed date for the Face to Face meeting and a word document with information listed Chapter 3.2 (annexe 1, 5.1)

Day 0

Admissibility

HAS

According to eligibility criteria and availability of HAS to the Face to Face meeting

Day 15

HAS comments – Pre Face to Face meeting TC

HAS, HTA bodies, EMA

Word document on the list of issues of the BB1 and possibly teleconference call (TC) with the company

Day 30

(max 1 month after BB1)

Briefing book version 2

(BB2)

Company

Word document with modifications implementing the list of issues

Day 45

(15 days after the TC)

Face to face meeting

HAS, HTA bodies, EMA / Company

Oral presentation by the company (based on a ppt presentation sent at least 8 days before the meeting) answers to questions by EMA, HAS, HTA bodies

Day 90

Report of the Face to Face meeting

Company

Word document based on template chapter 3.8 (Annexe 2, 5.2)

Day 105

Validation of the report

HAS

Modifications and final validation of the report

Day 120

 

If the timetable is not followed, HAS keeps itself the right to modify the date of the face to face meeting.

 

 

3.1 Request- letter of intent, briefing book version 1 and admissibility

At Day 0, the ED request is submitted to the Medicines Assessment Department of HAS via a letter of intent. This letter (word document) includes the brand name and the international common denomination of the drug, the claimed indication (be precised, for example state the line of treatment) and how the drug fulfils the 3 following eligibility criteria :

1)    clinical development must be ongoing: between phase II (results available) and phase III (under elaboration, not yet finalised and necessarily trials not started) ;

2)    the medicinal product must present a new way of treating a disease, a new mode of action;

3)    it must cover an unmet or poorly met need.

The request also includes the briefing book version 1 (BB1). This BB1 contains a description of the disease, the indication claimed, phase II data (efficacy and safety), and the development plan for phase III (overview of the development plan and design of phase III studies) and the substantiated questions it would like to ask with the company’s position. The questions have to be as precise and as clear as possible. They should primarily address scientific issues on clinical aspects (endpoints, choice of comparator …). “For more details, see annexe 1 (5.1)”

Where applicable, an outline of the proposed method for the production of the health economics assessment is attached to this dossier.

HAS decides on the admissibility of the ED, based on:

−     evidence to confirm that the product meets the three conditions set out above ;

−     the adequation of the question to the aim of EDs ;

−     the availability of the HAS team.

At Day 15, HAS confirms the admissibility of the early dialogue and proposes the date of the pre- Face to Face meeting conference call (CC) to the company.

Note: HAS keeps the right to cancel the ED if the briefing book does not contain information that fits with the letter of intent.

 

3.2 HAS comments, list of issues and Teleconference

At Day 30, HAS, with other agencies, will make an examination of the dossier. It may lead HAS to send to the company a list of issues or requests for additional data. If HAS has no comment, the TC is cancelled. If there are comments, a TC is organised.

The list of issues is provided by HAS by speaking with the company during the teleconference and in writing after the TC.

This list of issues contains the comments of HAS on the briefing book such as lack of data or information (does the material provided is sufficient to answer the questions), need for additional substantiation of some part of the BB, scope of the request, wording clarity of the BB, including the questions, repositioning of questions (if too wide or too narrow).

3.3 Briefing book –version 2

At Day 45, at least 15 days after the TC, the company sends a final BB (BB2) to HAS with all annexes and relevant publications. The ED will be conducted based on this version of the BB.

3.4 Face to face meeting

If significant/substantial changes are implemented into the BB2 they have to be notified as soon as possible to HAS. In this case a track changes BB2bis has to be provided at the latest three weeks before the Face to Face meeting with the reasons of the changes.

At Day 90, the Face to Face meeting aims to answer the questions raised by the company in its BB2. The company will provide its ppt presentation at least 8 days before the Face to face meeting. HAS defines the agenda of the Face to Face meeting on the basis of the questions. The usual agenda is the following:

-       General considerations

-       Presentation of the main points of the BB

-       Questions of HAS

-       Answers to questions of the company

-       Conclusions

3.5 Report of the face to face meeting

At Day 105, within 15 days to a maximum period of 1 month, the company prepares the report of the meeting. It contains:

−     a brief summary of the context;

−     a review of the target condition concerned;

−     the justification for the ED request, including the three aforementioned criteria ;

−     for each question : presentation of the question from the company, advice from HAS and possible comments made at the meeting ;

−     conclusions.

This report can be written in a standardised structure as detailed in Annexe 2 (5.2).

3.6 Validation of the report

By 15 days after the Face to Face meeting the report is validated by HAS (Day 120). It is kept by the company and HAS. It is not published.


4.  Management of confidentiality and ethics

HAS personnel are bound to secrecy by their employment contracts with HAS. This obligation guarantees the confidentiality of information brought to their knowledge. No additional confidentiality agreement submitted by the manufacturer will be signed by HAS.

Where applicable, experts approached by HAS commit to confidentiality when they sign the Public Declaration of Interests (PDI). When expert(s) are chosen, their PDI and any positive and negative conflicts of interest are taken into consideration.

Experts participating in these EDs cannot participate in the assessment of the product concerned. Therefore the members of the transparency committee cannot participate in these EDs.

 

English version

Posted on Apr 12 2016