Norway: On June 4th, it was announced that the National Research Ethics Committees (NEM) has revoked the Regional Ethics Committees for Health Research, REK Midt’s decision to grant ethical approval to a controversial study in which 120 ME patients were to be treated with the alternative treatment method Lightning Process.
The committee’s decision was unanimous. The decision is final and cannot be appealed. See link to NEM’s decision (in Norwegian) here.
On June 8th however, the research group sent a letter to NEM with a list of 15 points in order to «correct the facts on which NEM’s assessment is based upon and clarify some misunderstandings». The research group request NEM to reverse the decision.
The researchers claim a.o. that «There are thus no objective outcome measurements for improvement in CFS / ME…». This is in contrast to the fact that one of the researchers who signed the letter, Vegard B. B. Wyller, used pedometer (number of steps) as an objective outcome measurement in 2 of his own studies on the same patient group: the Clonidine study and the music therapy study.
The letter will be considered by NEM’s committee in a meeting on Tuesday 15th June 2021. Minutes from the meeting will be published after the minutes have been approved by the committee – which is at the next meeting in August 2021.
Below is an English translation of the letter (translated by me):
The National Research Ethics Committee for Medicine and Health Sciences, NEM
NEM´s ref: 2020/177 and REK´s ref: 101699 Date: 8 June 2021
We have received decision on the project «A 3-day intervention for CFS / ME» and will correct the facts on which NEM´’s assessment is based upon and clarify some misunderstandings.
- «NEM believes that the project’s greatest weakness is the research fellow’s active role in all stages of the project.»
Comment: The research fellow has no active role in recruitment, inclusion and randomization, collection, handling and analysis of data.
The various stages of the project are as follows:
a. Referral: The GP in the municipalities and others inform potential participants about the study and the intervention.
b. Application: Those who wish to participate apply for a course with one of the instructors in the project, where the research fellow is one of several.
c. Eligibility: Participants are assessed for participation in the usual way through a conversation based on stated criteria.
d. Inclusion: Neurologist Jone Owe at Haukeland Hospital includes participants based on patient records and stated inclusion criteria.
e. Randomization: The participants are externally randomized through a computer solution via the Clinical Research Unit Central Norway (KFMN) by a diagnostician at Haukeland University Hospital.
f. Measurements: Participants answer online questionnaires, where data goes directly to the statistician and monitoring committee.
g. Intervention: Participants participate in courses with several different instructors, where the research fellow is one of them.
h. Data analysis: Independent statistician conducts continuous interim analyzes and the monitoring committee checks data and analyzes.
i. Article writing: the entire research group participates in the work and is responsible for results, methods and the analysis, performed by statistician. The research fellow is one of at least seven authors, of which six have professorial qualifications.
2. «The research fellow will be an instructor on the course».
Protocol: See section 4.1 Recruitment, inclusion and exclusion. «Those who want to participate in the intervention apply for a place in the usual way with instructors who are involved in the project.»
Comment: The decision gives the impression that the research fellow is the only instructor, but the research fellow is one of several instructors who carry out the intervention in the project. The various instructors will conduct pre-talks, teaching and follow-up of the participants. This is because we want to test the effect of the intervention, not the effect of one instructor.
3. «The conflict of interest is most evident in the selection of the participants, which primarily takes place on the basis of a conversation with the research fellow.»
From REK application: Inclusion and randomization: «Those who wish to participate in the project« A 3-day intervention for CFS / ME» apply for a place on a course in the usual way with an instructor».
Comment: The decision gives the impression that only the research fellow will assess eligibility for participation in the intervention, but conversation before the course takes place in the usual way through conversations with the various instructors. The research fellow can leave his or her conversations with participants for other instructors to fully assess eligibility.
4. «Furthermore, NEM considers it a problem that the selection appears to be based on subjective assessments that the research fellow will make. Should the method and any effect have had transfer value, the selection criteria must be objective enough to be performed by others».
In our response to REK in October 2020, we wrote the following about eligibility: “The participant then has an interview with the instructor.
a. The interview is a clarification of expectations to ensure that the participants understand that they will participate in a lecturing with training in cognitive techniques, so that there is a clarification of roles, corresponding to a teacher and student situation.
b. The conversation is also a motivating conversation to strengthen the coping expectations for the intervention.
c. Participation presupposes a willingness to learn about the interaction between the brain and the rest of the body, a belief that this is relevant and an openness towards that change can take place through mental techniques and change in behavior.
d. Finally, it is clarified whether the participant has understood that following such a training program requires a commitment and a commitment to oneself, and that gaining access to knowledge and methods is not the same as guaranteeing changes.
e. Those who do not agree with all the points or have misunderstood this will not be relevant participants in the intervention».
Comment: There are several instructors who assess eligibility in advance of the course. These inclusion criteria are accurately described as above after input from REK. The reason why the standardized form is not attached and publicly available is to prevent anyone from signing up to deliberately destroy the study, as the research group has received signals that may happen. When the inclusion is completed, the standardized form will be published together with the manual for the intervention.
5. «There is a possibility that the method may cause that only those who initially have the greatest potential for improvement are included.»
Comment: NEM criticizes that we include those with the best prognosis. This may be, but it is countered with a randomized controlled design. If we manage to achieve a significant effect for those with a good prognosis, compared with a control group of exactly the same participants, then it is valuable and generalizable to this group. We plan to include based on coping belief, openness and understanding. If NEM is correct that this constitutes those with the best prognosis, any positive results from the study will have an impact on the patient group far beyond the effect of this particular intervention. The study will otherwise not be generalizable to everyone, as few studies are, but it will be generalizable to a significant proportion of a group of patients who currently have an almost non-existent offer of help. Participation in the intervention is not given as of today without the above criteria being met, nor will it be given in the future without the criteria being met.
6. «A weakness of the project concerns the evaluation of the effects of the intervention that takes place using a questionnaire».
Protocol: See section 3.1 Issues «1. Does a 3-day intervention for CFS / ME have a positive effect on physical function, fatigue, pain, post-exertional symptom worsening, mental well-being and quality of life in adult patients with CFS / ME compared with waiting list controls? Does the intervention have negative consequences for the participants?»
Comment: In research on behavioral interventions, it is common to use questionnaires to evaluate the effect of measures. This is because self-report is considered the gold standard for measuring, for example, pain and fatigue. Early in the process, we also considered including several potential objective measures (in addition to NAV data already included), such as actiometers and pedometers. (Translator added for clarity: NAV = The Norwegian Labour and Welfare Administration). These were dismissed as there is no basis in the literature for patients with CFS / ME moving less than others who are on sick leave and absence from school / work. Therefore, we chose measuring instruments based on the criteria for obtaining the diagnosis CFS / ME, which are not based on objective measures but on subjective self-report (eg subjectively reported fatigue, PEM and function). There are thus no objective measures for improvement of CFS / ME regardless of intervention / medical treatment.
7. «and that the intervention partly deals with how to respond to questions about one’s own health. NEM considers that the method poses a danger that the intervention may affect the responses from the participants for reasons other than real improvement».
Protocol: In section 2.6 A 3-day intervention: «There is a focus on language, and a distinction between passive and active language, which can increase awareness»
Comment: The intervention uses the linguistic term «I am doing», to increase awareness of what one is thinking, feeling or sensing. This can be compared with cognitive restructuring as is known from cognitive therapy, where one is challenged on the interpretation of symptoms and situations and gets to experience how this can lead to improvement. The question of «real vs non-real improvement» is therefore in this context corresponding to a distinction between «real vs non-real pain», and as is well known, pain is by definition a «subjective and sensory experience». In other words, there are no parts of the intervention that will be able to influence how one responds to questions about one’s own health that will explicitly influence the answers from the participants for reasons other than real improvement.
8. «As NEM has perceived the intervention, a central part of what the participants learn will be to ignore negative symptoms and focus on positive experiences.»
Protocol: In the case of chronic stress activation, the activation of the immune system can function as a «false alarm» which can be turned off by training new, positive expectations (Wyller et al., 2015b). During the 3-day intervention for CFS / ME, the participants learn to turn off the «false alarm», and an immediate impact on the perception of fatigue is expected.
Comment: It is common and important to change sensory perception in all therapy, and the participants learn to influence their own stress activation through regulation of thoughts and feelings. This is in line with the established theory «Cognitive Activation Theory of Stress» (Ursin & Eriksen, 2004). An important point in the lecturing is that the participants should avoid «pushing themselves», by ignoring symptoms and «push through». They are not supposed to «overlook negative symptoms». «Focusing on positive experiences» is the very core of positive psychology, a separate direction in psychology, which has been shown to give very good results for a number of disorders and conditions.
9. “They are also encouraged to use active language, to avoid thinking about their own limitations, and to reinforce their own progress.
Protocol: Section 2.6 A 3-day intervention states: «There is a focus on language, and a distinction between passive and active language, which can increase awareness».
Comment: This involves an increased awareness of one’s own thoughts, feelings and behavior, similar to cognitive restructuring in cognitive therapy, or defusing in Acceptance and Commitment Therapy. There are no parts of the course that say that you should avoid thinking about your own limitations. On the contrary, there is a segment about «not pushing oneself». The course content is described in the manual attached to the application.
10. «A change in the way of thinking will in a significant way be able to influence the answers given in the questionnaire immediately after the course».
Comment: This is a weakness in most of the research that is based on self-reported outcome measures, both in psychology and medicine and related fields, and is thus not unique to this study. Therefore, we have a randomized design with a control group with a 6 month follow-up period. Change in the way of thinking is an overrall goal in all psychotherapy and behavioral measures and is also not unique to our study. The questionnaires are validated and well-established and are used in all psychological CFS / ME research in general. The same questionnaires have also been used in drug studies with e.g. cancer medicine.
11. «The questionnaire also contains elements that in more indirect ways can indicate the effects of the intervention.»
Comment: We do not relate to eclectic «elements» as outcome measures, but only to validated questionnaires in their entirety. Measurable effect is desirable and with the exception of questions about advancing / inhibiting elements in the intervention, only validated measuring instruments have been used.
12. «NEM believes that it would have strengthened the project had there been more objective, primary endpoints in the evaluation»
Comment: Work participation is an important measuring point, both from a societal perspective and an individual perspective, which we therefore have included. Unfortunately, we have not found other relevant objective outcome measurements for which there is a scientific basis. We therefore considered the cost of including such outcome measures to be too high and without validity when weighed against the potential benefit we have reason to expect. Construct validity considerations do not allow for the inclusion of objective measurements in CFS / ME, as CFS / ME does not have any known objective biomarkers. This applies in the same way as for example for migraines, fibromyalgia and tinnitus.
13. «To counteract a possible conflict of interest, an independent statistician has been called in to ensure that the data cannot be affected and that no selective selection of analyzes is made.»
Protocol: See section 8.0 Ethics. Ethical considerations and approvals. «Therefore, special measures have therefore been taken concerning the design and implementation of the study to ensure that data cannot be influenced by the candidate. All collected data in the project goes directly to the statistician in the project at NTNU, so that the candidate does not have access to data until after the collection of the follow-up data. Analysis-file will be prepared without the candidate having knowledge of the intervention group / control group in the ITT analyzes of the primary outcome measure».
In our response to REK in October 2020: «Professor Mons Bendixen at NTNU is the project’s statistician and will present interim analyzes and data to the monitoring committee. The statistician has the overall responsibility for the analyzes, and guides the candidate on this, and will inform of all strategic choices in the analysis of the data to the monitoring committee, so that they can check that the analyzes follow common principles for scientific methods. The statistician has no vested interests in the outcome of the intervention and can therefore not be said to have a conflict of interest». Comment: The research fellow has no opportunity to influence the result-analyzes.
14. «It has been stated that the intervention may entail a risk of injury to the participants. This may in particular apply to negative reactions and possibly feeling of guilt in the event of a lack of improvement, as well as physical deterioration after increased activity in connection with the course ».
Protocol: 2.6 A 3-day intervention for CFS / ME. «The intervention also has several individual cases with rapid and big improvement than has previously been seen at CBT, and it is a more active approach.»
Comment: An active approach means that the participants must do something with their own thoughts and feelings. There are no parts of the course that indicate that participants should / must increase their physical activity. There is also no scientific evidence to expect physical deterioration due to the intervention. The one randomized and controlled study to date of a 3-day model showed no worsening or other adverse reactions in adolescents with CFS / ME.
15. «If society is to listen and have confidence in research results, it is important that there is no doubt in that the researcher is primarily guided by a desire to gain new knowledge in an objective and trustworthy way.»
In our response to REK in October 2020, we wrote the following: “All researchers have a preconception, in the sense of belief in their own hypothesis, and therefore conduct studies to investigate these. The key is to be aware of what preconception one has, and that the study design takes this into account, so that it does not have an impact on the analysis of data ».
Comment: In the same way as with all other research, there may be doubts about the researchers’ wishes and motivations. This applies in particular to research on controversial topics such as ME, climate, vaccines, salmon, wolves, opioids, etc. An ideal of full confidence in research is an important ideal that should be pursued, but which cannot be used as a premise for conducting studies in controversial fields. It will be stated in the article about «potential conflicts of interest», but the entire research group is responsible for the article’s content and independence, and it is study leader Leif Edward Ottesen Kennair who is the last author and finally «approves» the publication.
We have not used the name «Lightning Process» in the protocol or application, because we have wanted to make the study generic, as in transferable. The content of the intervention is described in the manual, but also described in detail in book form. This makes it easy for others to make interventions, as is already done both in Norway and in several other countries, but under different names. The municipalities have wanted access to knowledge from the project so that they can develop free services for the citizens.
The research fellow has been part of the public ME debate for more than 10 years and has both supporters and opponents without these being quantified. The study is important for generating new knowledge, especially since CFS / ME is a condition that typically affects women, and which affects many young people, but also because the economic costs for the society, both for the public health service and NAV, but also for the individual municipality. At the same time, the study will help to clarify an ongoing public debate. The results from this or other psychological studies will probably not change the position of the patient association regardless of the research fellow.
In light of the above corrections of facts and clarifications, we request NEM to reverse the decision.
Leif Edward Ottesen Kennair, Professor, Department of Psychology, NTNU
(translator added for clarity: NTNU = Norwegian University of Science and Technology)
Mons Bendixen, Professor, Department of Psychology, NTNU
Egil A. Fors, professor, Department of Community Medicine, NTNU
Silje E. Reme, Professor, Department of Psychology, UiO (translator added for clarity: UiO = University of Oslo)
Vegard Bruun Bratholm Wyller, Professor, Department of Internal Medicine and Laboratory Sciences, UiO
(End of letter)
See the original letter from the research group in Norwegian here:
Written by / translation by
Nina E. Steinkopf
Former HSEQ Chief Executive
Now; ME-patient and writer