The different steps of the HTA process

The five steps of the HTA process

STEP 1. Submission of a letter of intent to the EMA and the HTAR

Companies wishing to apply for marketing authorisation for a health technology submit a letter of intent to the EMA, which informs the HTA Secretariat, which in turn notifies the Coordination Group. This is done before the submission of an assessment application. The HTACG checks that it is relevant to the HTAR and notifies the JCA group.

The letter of intent is submitted approximately seven months prior to the start of the assessment, although a shorter time for the entire process is sometimes allowed for priority cases. Notice of priority treatment can be given a month before the start of the HTA process.

The application to the EMA is a parallel process in which the company submits its marketing authorisation application. The application or dossier contains that company’s scientific documentation regarding safety and effectiveness. The purpose of the HTAR is to demonstrate the relative quality of these two measures (see above).

The HTA Secretariat launches an assessment process once it has received the go-ahead from the EMA.

Depending on resource capacity, SBU will participate as assessor or co-assessor.

The entire process takes between nine and 14 months (one year on average). The process is dependent on the EMA’s timeline. The EMA’s parallel process includes “clock stops”, in which the company is able to temporarily halt the process to prepare responses to questions from the regulatory authority. A clock stop can, for example, last approximately three months. There is no such possibility in the HTA process, however.      

STEP 2. Determination of PICO

Defined questions are determined by a PICO framework. The process is based on the questions the member states want to have answered, so that each may decide whether or not to subsidise the health technology. 

PICO stands for Population (patient group or method), Intervention (that which is to be examined), Control/Comparators (comparison group), and Outcome, providing a framework for defining the JCA scope.

The PICO process

• Initiation phase. After the EMA and HTA Secretariate exchange information, the assessor and co-assessor are appointed (8 days).
• The assessor and co-assessor engage with experts and representatives of patient associations at an EU level to suggest the PICO. The assessor and co-assessor compile a preliminary PICO proposal (14 days).
• The proposal is sent via the IT platform to each member state, which is then able to add to it on the advice and recommendations of its experts and patient associations (approx. 21 days).
• The proposals are compiled (14 days).
• The proposal is reviewed by experts and by the JCA group (7 days).
• The PICO framework is compiled and finalised (7 days).
• The proposed PICO is presented to the company. An explanatory meeting is held with the company (20 days).

In this step, SBU will produce a relevant Swedish PICO from a patient perspective for all applications.

This step takes approximately 78 days.

STEP 3. Company dossiers

The dossier contains scientific documentation. The company submits a dossier containing data from clinical trials and preclinical studies along with other relevant information.

The company prepares the dossier on the basis of the established PICO and has 100 days to finalise and submit it (reduced to 60 days in the event of priority treatment).

Once the dossier has been submitted, a completeness check is made over approximately 36 days. At this stage, the HTA Secretariat can ask the company to submit additional information.

STEP 4. Preliminary JCA report

The assessor and co-assessor carry out a joint clinical assessment of the report under the supervision of the JCA group. The finished report is to summarise the relative effectiveness and safety of the health technology in question. A preliminary JCA report is drafted (draft 1).

The evaluator and co-evaluator judge, amongst other things, the literature search that the company carried out when preparing the dossier. An independent assessment is made of the risk of bias or outcome distortion for the constituent primary studies.

A statement of reliability is then presented concerning the effectiveness results per compiled outcome as determined by three concepts: i) internal validity (i.e. the extent to which a study is free from bias); external validity (i.e. the extent to which study results provide a basis for generalisation to the target population, a concept which encompasses generalisability and applicability); and iii) statistical precision (i.e. the uncertainty associated with study results due to random sampling variability).  

The company may view the preliminary JCA report in order that it may point out technical errors and to comment on any information that the health technology developer deems confidential. The company may also proffer additional information, data, analyses and other evidence it sees fit via the HTA Secretariat.

Depending on resource capacity, SBU will participate as evaluator or co-evaluator. The dossier is to be submitted 45 days prior to the EMA’s pronouncement, after which the EMA has 67 days to approve its source material. This step is estimated to take approximately 100 days (time permitting).

The finalisation of the JCA report:

• The JCA group reviews and discusses the preliminary JCA report, inviting independent experts in for consultation when necessary (21 days).
• The assessor or co-assessor prepares the second draft JCA report (7 days).
• Experts and patient organisations and the company comment on the second draft (7 days).
• The assessor or co-assessor prepare the third draft JCA report (14 days).
• The thirds draft JCA report is compiled and finalised by the JCA group (14 days).
• The Coordination Group approves the report (28 days).

As a member of the JCA group, SBU will check and present its opinions on all preliminary JCA reports.

The finalised report is then submitted to the Coordination Group for approval. The Coordination Group has 30 days from when the EMA issued its marketing authorisation decision concerning the health technology (a European Public Assessment Report – EPAR) to approve the reports.  Following the Commission’s formal examination of the process, the JCA report and the summary report are published.

STEP 5. Follow-up and decision

The joint clinical assessment at EU level is followed by national assessments for decisions on prices and subsidies. In Sweden, decisions on health technology subsidies are taken by the TLV.

All national HTA organisations are required to take the published JCA reports into consideration, and the reports should form part of the documentation used by authorities or bodies that are involved in HTA activities at member-state or regional level, and should be taken into consideration in HTAs at member-state level. The content of the reports is, however, of a scientific nature and should not be binding for these authorities or bodies or for the member states.