Spring over hovedmenu

Review of the correlation between exceptional stresses and the diagnosis of posttraumatic stress response/posttraumatic stress disorder (PTSD) with symptom onset and full diagnostic picture more than 6 months after exposure cessation (i.a. known as delayed onset PTSD)

Against the background of the judgement of the Danish Western High Court (Vestre Landsret) of 26th June 2020, Labour Market Insurance and the Occupational Diseases Committee have found that there is need for a more detailed review, if possible in the form of a scientific reference document, of the possible causalities between exceptional stresses and the development of symptoms consistent with the diagnoses of posttraumatic stress response, posttraumatic stress disorder (PTSD), and delayed onset PTSD.

A maximum of 600.000 DKK is allocated for this review.

The said review is urgent, not least out of consideration for the processing of PTSD claims of stationed veterans. If at all possible, a review report must be available before 1st June 2021.

It may be stated in the application if the deadline for submitting the report is not realistic. In that case, please state at what time the report will instead be submitted. The fund will make an overall assessment of content and quality of the applications, including whether the report will be submitted before 1 June 2021.

The grant recipient must make sure that enough time is set aside for the external reviewers to submit written comments, and for the grant recipient to respond to and possibly incorporate the comments in the report before the report is submitted.

Background

It is a well-known fact that exceptional stresses may lead to psychological symptoms consistent with the diagnosis of posttraumatic stress response or posttraumatic stress disorder.

The diagnosis of posttraumatic stress disorder is included on the Danish list of occupational diseases under item F.1. In Denmark the officially used diagnosis system is WHO-ICD-10.

One of the diagnostic criteria for this diagnosis is onset of symptoms within 6 months of exposure cessation.

In the DSM-5 diagnosis system, which is officially used in the USA, there is a sub-diagnosis, delayed onset PTSD, where the onset of symptoms occurs more than 6 months after exposure cessation. It should be noted that the exposure requirement for the diagnosis of posttraumatic stress disorder in DSM-5 is somewhat less strict than for the diagnosis of post-traumatic stress response in WHO-ICD-10.

The Occupational Diseases Committee in 2013, against the background of the PTSD review report ”A scientific review addressing delayed-onset posttraumatic stress disorder and posttraumatic depression”, laid down a practice for submitting claims, including the time criteria which had to be met in order for PTSD claims to be recognised.

However, in the judgement of the Western High Court of 26th June 2020, the medical criteria for time correlation between the exceptional stresses and the development of PTSD which had previously been set out were set aside against the background of the medical assessment made by the Medical Examiner’s Council (Retslægerådet). Therefore, based on the assessment made by the Medical Examiner’s Council, the judgement changes the medical assessment of time correlation. Thus the Council expressed the view that they did not agree with what it takes to establish causality in PTSD cases or the evidence assessment required in such cases.

As no new criteria, medical criteria included, can be derived from the judgement of the Western High Court of 26th June 2020 with regard to time correlation, and because therefore it is not possible to set out specific guidelines for the future submission practice of the Occupational Diseases Committee, there is a need for a new medical review/independent medical research report for the elucidation of whether more recent medical research supports a changed approach to the assessment of PTSD cases, specifically and in particular with regard to time correlation, which is where the judgement in particular challenges previous practice.

Project framework

Against the background of a primarily epidemiologically based examination of international research results in the field, the scientific reference document will elucidate in detail, summarise and assess knowledge of  causalities between exceptional stresses, short- or long-term, and the development of symptoms consistent with the diagnoses of posttraumatic stress response, posttraumatic stress disorder (PTSD) and delayed onset PTSD. The review shall elucidate symptom onset consistent with later than after 6 months for posttraumatic stress response.

There will be an assessment of the evidence of such possible correlation and an estimate of any risk in relation to the nature, severity and duration of the exposures.

The assessment shall take into account the current diagnostic criteria ICD-10, the upcoming ICD-11 criteria, as well as the DSM-5 criteria.

For possible work-related posttraumatic stress response, posttraumatic stress disorder and delayed onset PTSD, the following information is needed:

About the disease:

  • Information about how the diagnosis is delimited and specified
  • Specific information about how the diagnosis was made
  • An assessment of the validity of the results
  • Information about the severity of the disease

About time correlation between exposure and onset and full PTSD

  • Information about the time that passed from exposure cessation till onset of the disease and full diagnostic picture. Disease onset is to be understood as the time when the symptoms began and not the time when the person first contacted a doctor or other health professional (it is allowed, of course, to include such information)
  • A clear description and assessment of the disease onset time in relation to exposure period/exposure cessation
  • An assessment and analysis of how much time typically will pass – and not least the maximum time – between exposure cessation and the first symptoms of the disease until full onset, so that there still is definite causality between the original stresses and the subsequent PTSD
  • Is it significant for the development of the disease and the time correlation that the exposure occurred in connection with work, as opposed to if the exposure is unconnected with work? If so, how significant?

About the exposure:

  • The nature of the exposures and the type of work/employment in question
  • The more specific nature and intensity/scope and duration of the exposures
  • Correlation between the intensity/scope of the exposure and the risk of developing the disease
  • An account of how the exposure is qualified and how it might have been verified

About the causality:

  • A summarising description and assessment of any dose-response correlations
  • The relationship between the frequency of traumatic stress response, posttraumatic stress disorder (PTSD) and delayed onset PTSD
  • A clear description and assessment of the duration of the exposure, including in particular the impact of any “breaks” in the exposure and the significance of reactivation
  • An assessment of the prognosis, including the impact of the exposure on the prognosis
  • An assessment of the time requirement between stresses and onset in relation to the time that may pass in order for there to be causality with stresses

About competitive and pre-existing diseases/factors:

  • Description of the significance of competitive and pre-existing diseases for the disease development
  • Description of the significance of non-occupational cause factors, including exposures in the private sphere
  • Description and any significance of heredity, gender and age
  • If possible, an assessment of the role played by occupational stresses in relation to non-occupational factors with regard to the development of the disease, including when the private stresses and the occupational stresses occur in relation to PTSD onset. It should be stressed that the stresses must occur in connection with work in a professional environment.
     

Summary:

  • An account of whether it is possible to identify a time requirement between stresses and disease onset and full presence of the disease. The quite crucial element is an analysis of the typical maximum time passing between exposure cessation and disease onset, so that there still is definite causality between the original stresses and the subsequent PTSD
  • An account of the significance of reactivation
  • A description and assessment of the reliability of the exposure description and disease documentation in the individual article
  • A summarised and graduated assessment of the evidence of a correlation, in particular with regard to the time requirement between exposure and onset/full PTSD (see special guidelines for reviews of occupational diseases)
  • The significance of gender data and differences for the development of the disease
  • Is it significant for the development of the disease and the time correlation that the exposure occurred in connection with work, as opposed to if the exposure is unconnected with work? If so, how significant?
  • The project report will include a summary in Danish, directed at lay persons

If there is insufficient evidence of a correlation between the exceptional stresses and the diagnoses of posttraumatic stress response, posttraumatic stress disorder (PTSD), and delayed onset PTSD, or if the literature is otherwise inadequate, this will be stated and specified.

If it is found that additional research should be initiated, the relevant efforts and goals for further research should be pointed out, substantiated and included in the overall conclusion of the project.

Special guidelines:

The preparation of the review must follow the special guidelines for preparation and quality approval of reviews in the form of reference documents in the field of occupational diseases. The current edition of the guidelines is found below.

Special guidelines for preparation and quality approval of reviews in the form of reference documents in the field of occupational diseases

November 2010
(1st July 2016: The National Board of Industrial Injuries (Arbejdsskadestyrelsen) changed name to Labour Market Insurance (Arbejdsmarkedets Erhvervssikring/AES))


The objective of preparing a reference document in the field of occupational diseases is to provide the best evidence-based answers to questions regarding possible causalities between various types of work-related exposures and the development of various types of diseases/complaints.

Therefore, with a view to ensuring the highest possible targeted quality of the required scientific literature examination, the following special guidelines have been set up for preparation and quality approval of a reference document in the field of occupational diseases.

  1. In connection with carrying out the project, the applicant will point to three or four external experts in the research area in question as relevant and competent reviewers. The Working Environment Research Fund (Arbejdsmiljøforskningsfonden) quality approves all reviewers and finally appoints two of those reviewers for the further process. All costs deriving from the work of the two reviewers will form part of the overall financial budget of the project, cf. the guide to application for subsidies from the Working Environment Research Fund. Budgets must be kept within an overall frame of DKK 50,000 for the reviewers’ work. Once the reviewers have been finally appointed by the Fund, a detailed budget for the project will be determined and approved by the Fund.
  2. The reference document must be prepared according to the requirement specifications of the notice and will also, in addition to the budget, include a detailed plan for time consumption and deadlines for each phase of the project, including for the reviewing phase.
  3. Within one month after receiving the applicant’s first final draft, the two reviewers will prepare and deliver to the applicant their written comments on the document.
  4. The subsidy recipient will write the final conclusion of the manuscript, in accordance with the comments received, and the revised work will be forwarded to the reviewers for any new comments. If needed, there may be one or more rounds of changes and comments in this conclusive part of the process. If it is not possible to reach a final agreement on the evidence basis and conclusions in connection with the conclusive evaluation of the work, such disagreement, and the specific origin of it, will appear explicitly from the final document. Any disagreement will be set out separately in the document.
  5. The final document with incorporated contributions from reviewers will be delivered to the Fund within the agreed time limit for conclusion of the project.
  6. The reference document will be delivered in an English version, including an exhaustive Danish summary. The summary will focus in particular on answering the most substantial, overall questions of the notice, including in particular a summary of conclusions regarding causalities between exposures and disease(s) and the respective evidence levels.
  7. In connection with the assessment of the evidence, the subsidy recipient will apply the recognised evidence model seen below – Guidelines for establishing a reference document on the causal relation between an occupational exposure and a disease outcome. In the event of the exceptional application of any other evidence model, such a model is required to give a presentation of evidence which is just as clear and transparent, based on equivalent principles.
  8. The subsidy recipient will be under an obligation to personally present the results of the project, including the main conclusions of the reference document and the work method applied, to the Occupational Diseases Committee. Arrangements will be made with Labour Market Insurance. The presentation will in principle be made not later than two months after conclusion of the project.
  9. As soon as Labour Market Insurance and the Occupational Diseases Committee have finalised their negotiations on the review, Labour Market Insurance, in connection with publishing the results of the negotiations, will also publish the reference document on their website www.ask.dk. This will also appear from any press release.
  10. The subsidy recipient must hold back his/her own publication of the reference document and its results, including part results, until Labour Market Insurance has reported back to the subsidy recipient that negotiations have been concluded and that the document may be released for own publication. The time of publication/release of the document and its results, including part results, cannot be determined in detail, this depending on the course of the negotiations.
  11. In connection with any own publication of the reference document and its results after release by Labour Market Insurance, the subsidy recipient must state that the document was written on the initiative of Labour Market Insurance and the Occupational Diseases Committee and that the reference document can also be found on the website of Labour Market Insurance www.ask.dk.
  12. In the event of an own publication of the reference document and its results after release by Labour Market Insurance, the Board will receive a copy of the subsidy recipient’s own published versions of the review and its results.
  13. The subsidy recipient and reviewers must not be members of the Occupational Diseases Committee or employees of wage-earner or employer organisations or Labour Market Insurance.
    Further reference is made to the current standard terms for subsidies from the Working Environment Research Fund. These standard terms also apply to the preparation of reference documents.
     

Guidelines for establishing a reference document on the causal association between an occupational exposure and a disease outcome

(The Working Environment Research Fund)

Guidelines for manuscripts of reference documents

The aim of establishing a reference document is to provide the best evidence-based answers to questions on the causal relations between an occupational exposure and a disease outcome.

The reference document should be written in English and should be supplied with an extended popular summary. The text part of this summary will be translated to Danish. The reference document, tables and appendices will not be translated. 

The reference document should be written in a form, which is suitable for publication in a peer-reviewed international journal. The word count of the main text should not exceed 8000 words.  If the requirements outlined below (e.g. text summaries of key studies) imply that the review becomes too long for such a publication, some of the detailed information may be put in an appendix and only summarized in the main text.

The manuscript should be organised as follows:

1. Background and delimitations of the task to specific diagnoses and exposures

2. The outcome under study

-        Clinical diagnosis and proxy-measures used in epidemiological studies.

-        Exclusions of certain conditions from the study.

-        Risk factors for the outcome (excluding the exposure under study).

-        Descriptive epidemiology, incidences and prevalences of the outcome.

Preferably, literature references in this section should be to high quality reviews rather than original papers, since this introductory section is not based on a separate literature review by the authors.

This section should be oriented towards problems to be discussed in subsequent sections.

3. The exposure under study

-        Definition of the exposure.

-        Measurement of the exposure. 

-        Distribution in the general population and occupational groups.

Preferably, literature references in this section should be to high quality reviews for the reasons given above.

This section should be oriented towards problems to be discussed in subsequent sections.

4. Literature search

-        Description of search terms, databases searched, date of final search and number of references.

-        Description of the procedure followed to arrive at the studies that are considered in the document (inclusion and exclusion criteria and the methods used to apply them).

-        If the final set of references includes a large number of studies (e.g. more than 25-30 studies per outcome) it is recommended to include only the studies that are most informative with respect to the issue (key studies).  The procedure used to get to these studies must be described and documented.

-        A flow-diagram of the literature selection should be included. 

5. Literature review

The final set of references from the literature search should be described in text and tables, study by study. The text should shortly present essential details of the study and provide the reader with a good impression of its distinguishing features, strengths and limitations, and should include evaluative comments by the authors of the reference document. More important studies are presented with more detail than less important ones. Critical comments on the individual study should be given [in square brackets] in this section.

If there are more than 25-30 references per outcome, only the key studies on which the conclusion is based need to be described in the text. The remaining articles should be described in an independent table corresponding to the table of the more informative studies. The purpose of this selection is to move quickly to the more important studies and not having the presentation mixed up with detailed descriptions and results from less informative studies.

6. Quality assessment of a specific study

In addition to systematic assessments of study quality using formal scoring systems, the quality of studies reviewers are encouraged to qualitatively assess the results of each study with respect to the likelihood that they may reflect chance, bias or confounding, and to assess the external validity of the study results. Quality should not be assessed only by a formal scoring system since there is no ‘gold standard’ for the true validity of a study. 

7. Other relevant data

Other relevant data from human or animal, observational or experimental studies should be referred to. The assessment of plausible disease mechanisms to support a cause-effect relation may typically rest on such contributing evidence. The description of contributing evidence may rely on good reviews rather than original studies.

8. Discussion

The discussion should consider the whole set of results from the studies included in the reference document, and especially consider the degree to which it may be assumed that bias or confounding could explain the overall results. The discussion should aim at clarifying the main arguments pertinent to the overall conclusion on causality based on the literature review. 

The discussion should deal with the diagnostic entities used in the epidemiological studies in the review compared to diagnostic criteria in clinical practice, the reliability and validity of the outcome measures used in different studies.

The discussion should further deal with problems of exposure assessment relevant to the problem, including reliability and validity. Inaccuracies in diagnosis or exposure assessment should be discussed with respect to the direction and magnitude of the resulting bias of the exposure-outcome relation. 

Furthermore, the discussion should consider the effects of potential confounding or effect modification which was not accounted for, and the degree to which the overall results may be influenced by such uncontrolled confounding or effect modification.

The different arguments relating to bias and confounding of the relation between outcome and exposure should be detailed and summed up in a manner that clearly explains and justifies the conclusion.

9. Conclusion

The conclusion should start by describing the premises on which it is made. It should be a natural extension of the discussion and shortly declare the degree of evidence for a causal association between the outcome and exposure under consideration. The degree of evidence is described with a view to the classification scheme on the last page of these guidelines, but must verbally reflect the opinions of the authors in sufficient detail. However, the conclusion should be short and to the point. If it is concluded that there is strong or moderate evidence of a causal exposure-effect relationship, the exposure-response pattern of this relationship should be described – and if possible translated to a practically useful exposure measure. If several outcomes or exposures are included in the review, there must be a conclusion for each specific relation.

10. Abstract

11. Extended popular summary

The extended summary must give an accurate account of the work and especially focus on an argued response to the questions raised in the task description. The language should be straight forward and technical terms should be avoided. The summary is aimed at informing the organisation that funded the work, decision makers and the public at large on the background, results and conclusions of the work. The extended popular summary will be translated to Danish.