Translation and Validation of the COMM and ASI-SR - Instruments for Assessing Substance Use Disorder Development in a Swedish Population of Patients With Long-term Pain Treated With Opioids
Conditions: Opioid Use, Opioid Use Disorder, Alcohol Use Disorder, Pain, Chronic
Sponsor: Uppsala University

Translation and validation of the COMM and ASI-SR – instruments for assessing substance use disorder 
development in a Swedish population of patients with long-term pain treated with opioids 
 
 
 
 
 
 
 
Principal Investigator (PI): Rolf Karlsten, Assoc. Prof. 1,2 
Coordinating researcher: Lenka Katila, PhD Student1,2 
Co-researcher: Pernilla Åsenlöv, Professor1,3;Hanna Ljungvall, PhD 1,3;  
Magnus Peterson, PhD4,5, Anna Svensson,4,5 ;Annica Rhodin, PhD 1;  
Torbjörn Åkerfeldt7,Kim Kultima, PhD7; 
Statistician: Anders Berglund, PhD6 
 
Study code: COMMISS 
 
Responsible sponsor: Region Uppsala, Uppsala county, Sweden 
1 VO Rehabilitation and pain center, Uppsala University Hospital, Sweden 
2 Department of Surgical Sciences, Uppsala University, Sweden 
3 Department of Women's and Children's Health, Uppsala University, Sweden 
4Department of Public Health and Care Sciences, General Medicine and Preventive 
Medicine, Uppsala University, Sweden 
5 Primary Care, Region Uppsala, Uppsala county, Sweden 
6 Clinical Neuroscience, Statistics Academy Karolinska Institute, Stockholm, Sweden 
7 Department of Medical Sciences, Uppsala University, Sweden 
 
 
Translation and validation of the COMM and ASI-
SR – instruments for assessing substance use 
disorder development in a Swedish population 
of patients with long-term pain treated with 
opioids 

Translation and validation of the COMM and ASI-SR – instruments for assessing substance use disorder 
development in a Swedish population of patients with long-term pain treated with opioids 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Translation and validation of the COMM and ASI-SR – instruments for assessing substance use disorder 
development in a Swedish population of patients with long-term pain treated with opioids 
 
 
1 Introduction 
Long-term opioid therapy is one of  the methods of treating long-term pain that in many 
cases leads to problematic use, development of addiction and complications.[1] 
Effective screening and risk assessment is important both before treatment begins, but 
also continuously during treatment. At the moment, there are no relevant or sufficiently 
sensitive questionnaires in Swedish for assessing risk development for opioid addiction 
in pain patients treated with opiods for long-term pain. Many instruments have been 
evaluated abroad and the ones with the greatest relevance are "Screener and Opioid 
Assessment for Patients with Pain" (SOAPP) [2] for assessment before starting 
treatment and "Current opioid misuse measure" (COMM) for control of ongoing 
treatment[2-5]. The Addiction Severity Index (ASI) is also a standardized assessment 
instrument, validated for assessment of general addiction problems. It contains a 
standardized semi-structured interview for the assessment of past and current 
problems in seven different areas; physical health, work/support, alcohol use, drug use, 
family/association, legal problems and mental health[6]. It is a time-consuming 
interview. A shorter version, the ASI-SR, has been validated for assessment in a Swedish 
population [7] and reflects more on ongoing problem. However, it is not specifically 
intended for, or validated, for pain patients with preferential iatrogenic use. 
We therefore plan to translate the COMM form and validate it using the ASI-SR in a 
Swedish population of pain patients treated with opioids. At the same time, the 
prevalence of illicit substance use will be investigated in this population and compared 
with patients who are not treated with opioids. Inflammatory markers will be collected 
in Uppsala Biobank for future analyzes of neurobiological processes during the 
treatment of long-term pain. When this becomes relevant, a separate ethical application 
will be made. 

Translation and validation of the COMM and ASI-SR – instruments for assessing substance use disorder 
development in a Swedish population of patients with long-term pain treated with opioids 
 
 
2. Background 
 
The use of opioids for long-term pain is related to an increased risk of developing 
addiction and complications, such as neuropsychological disturbances, depression, sleep 
disturbances, risk of overdose and even death. [1] 
Long-term opioid therapy (LOB) for the treatment of long-term pain has not been shown 
to outweigh the risks and complications it may cause for most of the patients. The 
International Association for the study of Pain IASP stated in February 2018 that opioids 
should be reserved only for a group of specially selected patients, for a limited time and 
in a limited amount, and even then patients are at risk of developing these 
complications[8]. Thus, selection of a suitable patient as well as further strict controls of 
the treatment can be critical in reducing the risk of addiction development in these 
patients. Although pain patients in many cases meet criteria for substance dependence 
syndrome according to ICD 11 and DSM V classification, this dependence is not driven 
by the drug itself but by relief from pain [9]. 
 
Several methods for assessing the risk of opioid addiction have been evaluated, but none 
of them alone have shown sufficiently good results, which is why combinations of 
several methods are advocated. Medical, psychosocial and disease history from both 
patient and relatives has a central role. Young age (below 45 years) and male gender is a 
predisposing factor, but age and ethnic factors do not seem to be consistent in different 
studies [10, 11]. Urine drug testing is often cited as a gold standard for monitoring, but 
there is no evidence to support its accuracy, effectiveness in predicting, preventing, or 
reducing problematic behavior or fatal complications such as overdoses and death[10, 
12-14]. Urine testing in pain clinics and health centers is problematic due to a lack of 

Translation and validation of the COMM and ASI-SR – instruments for assessing substance use disorder 
development in a Swedish population of patients with long-term pain treated with opioids 
 
 
appropriate facilities and embarrassment for the patients. Analysis by high-performance 
liquid chromatography and mass spectrometry of saliva samples has been compared 
with urine samples and shows a high detection rate and overall agreement regarding the 
results in 85%.[15, 16] Thus, saliva testing can be a suitable replacement for urine 
samples due to easier sampling and less impact on integrity. A weakness of saliva tests is 
cannabis analysis, as it can only be detected in saliva two days after use. One possibility 
to increase the detection window to 2-3 weeks is to analyze cannabinoids from capillary 
samples, Dry blood spot, with the same analysis methods[17]. Alcohol use is most 
suitable to be analyzed with Phosphatidylethanol sample in the blood (PETh)[18]. These 
laboratory methods would partly be good for validating questions related to the use of 
illicit substances in COMM, but also provide answers to the question what is the 
prevalence of substance use syndrome in the pain population treated with opioids. 
Today's high patient flow both in primary care and in hospitals makes long time-
consuming interviews impossible, and clinics often have limited time for assessing the 
patients. Effective, digitalization-friendly instruments for risk assessment are therefore 
desirable. 
There are some instruments in English, which were developed for risk assessment 
before LOB: Opioid risk tool (ORT)[19], Screener and Opioid Assessment for Patients 
with Pain (SOAPP) and its short version SOAPP-R (which is suitable for computerized 
collection of data)[20, 21], the Addiction Behavioral Checklist (ABC) [22] and the 
Physical Opioid Therapy Questionnaire (POTQ)[23]. 
Then there are others that are more suitable for ongoing treatment of LOB: Prescription 
Drug Use Questionnaire (PDUQ)[24, 25] or Prescription Drug Use Questionnaire-Patient 
version (PDUQ-p), Pain Medical Questionnaire (PMQ) or Modified Pain Medical 
Questionnaire (mPMQ), Prescription Opioid Misuse Index (POMI), Pain Assessment and 

Translation and validation of the COMM and ASI-SR – instruments for assessing substance use disorder 
development in a Swedish population of patients with long-term pain treated with opioids 
 
 
Documentation Tool (PADT), Prescribed Opioid Difficulties Scale (PODS) and Current 
Opioid Misuse Measure (COMM). Furthermore, there are other instruments for 
assessing all types of addiction that are not specific to opioids, such as DSM-IV, CAGE 
questionnaire, Addiction Severity Index, Michigan Alcohol Screening Test, Minnesota 
Multiphasic personality Inventory, Screening Instrument for Substance Abuse Potential 
[26, 27 ]. 
Many experts state that the evidence is insufficient for any of these instruments to have 
an effect in healthcare [13, 22, 28]. Many are too long and unrealistic to use in clinical 
practice [29]. Compilation of results for sensitivity and specificity of the various 
instruments both before and during ongoing LOB by Chou and colleagues can be found 
in Tables 1 and 2 below [10]. 
Table 1: Optimal balance between specificity and sensitivity of  instruments before the start.  
Of COT: 
Tool 
Sensitivity 
Specificity 
Study refferens 
SOAPP>7 
0.91 (95% CI, 0.78-
0,98) 
0,69 (95%,CI,0,54-0,81) 
Butler 2004 
SOAPP>8 
0,68(95%, CI, 0,52-
0,81) 
0,38 ( 95% CI, 0,29-0,49) 
Akbik 2006 
SOAPP-R 
score >18 
0,80 (95%CI, 0,70-
0,89) 
0,68 (95% CI, 0,60-0,75) 
Butler 2008 
ORT>8 
Not applicable (not 
dichotomous) 
Not applicable (not 
dichotomous) 
Webster 2005 
 
Table 2: Optimal balance between specificity and sensitivity of  instruments for 
detection of misuse during COT (Enligt  Chou et al 2009  ) 
Tool 
Sensitivity 
Specificity 
Study/quality 
COMM (17)>10 
0,74 (95%CI, 0,63-
0,84) 
0,73 (95% CI,0,65-
0,80) 
Butler 2008 …5/9 
ABC(20)  3 of20 
0,88 
0,86 
Wu 2006, 4/9 

Translation and validation of the COMM and ASI-SR – instruments for assessing substance use disorder 
development in a Swedish population of patients with long-term pain treated with opioids 
 
 
PDUQ 
0,74 (95%, CI, 0.63-
0.82) 
0,57 (95% CI, 0,49-
0,65) 
Wasan 2007 6/9 
 
COMM was developed in the USA by Butler et al and shows promising results in the 
follow-up of pain patients with COT in primary care and the detection of patients at risk 
in acute care [30, 31]. 
A combination of the prescriber's assessment, SOAPP-R before the start of treatment 
and COMM during ongoing treatment and possibly random drug testing can predict SUD 
risk during opioid prescribing in the next 12 months [31]. 
The original article on COMM has identified 5 question areas (clusters) that the 
instrument assesses: 
1. Symptoms and signs of drug abuse (question 1) 
 2. Emotional and psychiatric problems (questions 2,5,7,8,13) 
 3. Visitor characteristics/patterns (questions 3,12,17) 
4. Evidence of untrue statement (doubt/lie/untruth) and drug use (questions 
4,6,9,10,11) 
5. Medication use and deviation from prescription (non-compliance) (questions 
14,15,16). [4] 
The short version of the ASI-SR has recently been translated into Swedish and validated 
for assessment of addiction problems and reflects 7 different areas of life: physical 
health, professional life, alcohol use, drug use, family and social life, criminality and 
mental health [7, 32] Thus, this instrument can be relevant as a reference for clinical 
assessment of dependence development in patients with LOB. 
Our hypothesis is that COMM and ASI-SR are suitable forms for assessing the 
development of addiction among pain patients, which the patient can also fill out 

Translation and validation of the COMM and ASI-SR – instruments for assessing substance use disorder 
development in a Swedish population of patients with long-term pain treated with opioids 
 
 
digitally before the visit and will thus not burden the healthcare staff in terms of time. 
COMM is specifically developed for patients with pain and iatrogenic treatment with 
opioids in contrast to ASI-SR and may thus be more relevant. On the other hand, ASI-SR 
can better identify possible mental illness, criminality and be more sensitive to alcohol 
issues, which COMM does not clearly address. 
The next aspect is whether a Swedish patient differs markedly from an American one, as 
the COMM was developed for the American population. It has now been translated into 
several languages and the first validations show good results ([33, 34]. Similar to the 
USA, many patients in our clinic have been introduced to opioids in primary and 
specialized care, but not via the pain clinic [35] . Prescription of strong opioids, 
especially oxycodone per capita is increasing dramatically, even though the total amount 
of opioids prescribed is decreasing. This trend seems to have been stable in Sweden for 
the last ten years [36]. On the other hand, Sweden has among the highest drug-related 
mortality per capita in Europe [37]. Although mortality related to prescription opioids in 
Sweden does not appear to be as dramatic as in the United States, the trend in the 
prescription of strong opioids is alarming and control mechanisms are needed to 
prevent a negative development in the future. Above all, an increased trend in 
oxycodone prescription and its correlation with oxycodone-related deaths in Sweden is 
alarming[38]. 
We plan to translate and validate the COMM as well as validate the ASI-SR for use within 
a Swedish population of patients with long-term pain and ongoing opioid treatment and 
examine internal validity in the Swedish population. 
Furthermore, the correlation will also be examined against our external validity 
measures regarding pain, addiction, mental health, visitor characteristics, compliance 
with the treatment and secondary use of substances. 

Translation and validation of the COMM and ASI-SR – instruments for assessing substance use disorder 
development in a Swedish population of patients with long-term pain treated with opioids 
 
 
The survey also plans to answer the question regarding the prevalence of alcohol and 
other substance use is in patients with long-term pain and opioid treatment in Sweden. 
Opoids are considered to strongly affect the neuroinflammatory processes linked to the 
development of both different types of chronic pain and addiction. Blood samples are 
continuously being collected at the Uppsala pain center for the examination of 
biomarkers and DNA analysis within the U-Pain project. For example, studies of 
differences in biomarkers between patients with chronic pain with and without opioid 
therapy can provide important information about the underlying processes of many of 
the side effects we see from LOB. For any studies regarding biomarkers and genetic 
tests, separate ethical applications will be made. Therefore, the collection of blood is also 
planned for this purpose. 
3. Aim 
The primary aim is to translate COMM into Swedish and examine its reliability and 
validity against the ASI-SR in a Swedish population of pain patients with LOB. 
The secondary aim is to investigate acceptability of the instrument in a Swedish 
population of pain patients with LOB. 
The tertiary aim is to investigate the prevalence of alcohol and illicite substance use in a 
Swedish population of pain patients with LOB. 
Samples will be collected to be able to study biomarkers and genetic analyzes at a later 
stage for a better understanding of mechanisms behind long-term pain. However, this is 
not part of this validation. These samples may be examined with the O-link 
neuroinflammatory panel and future genetic analyses, whereby a separate ethical 
application will be made. 
 
 

Translation and validation of the COMM and ASI-SR – instruments for assessing substance use disorder 
development in a Swedish population of patients with long-term pain treated with opioids 
 
 
4. Methods: 
Phase 1: 
Translation of the instrument takes place according to the "Patient-Reported Outcome 
(PRO) Consortium translation process guidelines" [39] and according to guidelines from 
the company MAPI Trust, which owns the rights to use the instrument. The process is 
described in the table below. 
 
Step Name Description of the process Actor/responsibility 
1. Preparations  
Request for rights for translation and validation of instruments for research and 
clinical use from COMM developers, company: Mapi research Trust. 
Contract with a Swedish professional translator (Accent Language Service Umeå). 
Lenka Katila applies. 
 
Granted by Birgitte Leroux, Mapi research Trust, 16.7.2020. 
2.  Translation into Swedish 
Translation into Swedish takes place with two translators; a professional 
translator and a researcher. Lenka Katila, researcher, 16.7.2020. 
 
Evalotta Boman, Accent Language Service. 
3. Reconcilliation I 
Both translations are compiled, compared and the best Swedish version is 
produced. Lenka Katila and Evalotta Boman 
4. Backward-translation into English  
Another professional translator back-translates the compiled Swedish version, 
without seeing the English original. David Ordoubadian, Accent Language Service. 

Translation and validation of the COMM and ASI-SR – instruments for assessing substance use disorder 
development in a Swedish population of patients with long-term pain treated with opioids 
 
 
5. Reconcilliation II  of the compiled translation after comparison of the back 
translation  
Evaluation of back translation to achieve semantic equivalence and identify 
problems with the translation, compilation of versions and possibly make 
changes to the translation. Hanna Ljungvall, Rolf Karlsten, Pernilla Åsenlöf, 
 
Stephen Butler 
 
6. Professional reading  
Two or more independent professional readers check translation, correct 
diacritical marks and grammar and a clinical expert in the field performs this step 
in parallel. Clinical expert: Expert and linguist: Annica Rhodin 
 
Language expert: Per Sellius 
7. Cognitive interviews  
Conducted on five Swedish-speaking individuals, with different backgrounds, age 
and gender, and with long-term pain treated with opioids of various types. The 
interview will specifically examine whether all words are understood correctly, 
as well as that the respondents understand the question in the same way and that 
they perceive the answers as relevant and appropriately described. 
 
Lenka Katila, Hanna Ljungvall 
 
5.10.2022 
  
8. Evaluation of cognitive interview  
The answers in the cognitive interviews are evaluated and compiled, feedback is 
presented to the translation team. Any revisions of the text are carried out and a 

Translation and validation of the COMM and ASI-SR – instruments for assessing substance use disorder 
development in a Swedish population of patients with long-term pain treated with opioids 
 
 
final revised version of the text is compiled. Rolf Karlsten, Lenka Katila, Hanna 
Ljungvall,  Annicka Persson Rhodin, Pernilla Åsenlöv 
 
9. Final revision and documentation (Proof reading).  
Review so that the proposed revision maintains conceptual equivalence and does 
not pose a risk to international harmonization of any future revisions, the 
proofreader's revised translation, or other relevant alternatives. Final 
professional reading and adaptation to the original graphic model 
(format/layout) as well as adaptation both for paper and screen, to avoid any 
problems with data collection. Rolf Karlsten, Lenka Katila, Hanna Ljungvall, 
Pernilla Åsenlöv , Alexander Rosendahl 
10. Report  
Final report with documentation and description of all steps and decisions. Lenka 
Katila 
12. Archiving Documentation that is archived: 
- The qualifications and experience of the translation team 
- Documentation of changes made during the translation process and reasons for 
changes 
- Translation certificate 
- Translation report including results of cognitive interviews Lenka Katila 
 
Phase 2: 
The next step is validation of COMM against ASI-SR in a Swedish population of patients 
with long-term pain according to the Cosmin guidelines [40] with the following steps: 

Translation and validation of the COMM and ASI-SR – instruments for assessing substance use disorder 
development in a Swedish population of patients with long-term pain treated with opioids 
 
 
1. Test of reliability for internal consistency, test-retest consistency and standard error 
of measure (SEM) and factor analysis with rotation in a Swedish population of patients 
with long-term pain and LOB. 
2. Investigate COMM's validity regarding comprehensivity/scope and 
comprehensiveness/user-friendliness- and predictiveness/predictability in this 
population. 
3. Investigate whether the instrument is acceptable in the population. 
4. Investigate prevalence of illicit substance use parallel to LOB in pain patients and 
compare with opioid-free pain patients. 
We plan to recruit 200 research subjects in the test group, both from primary care, 
specialized pain care, other specialized care (e.g. Endometriosis Center) and from 
addiction care (addiction medicine program for pain patients). In addition, it is planned 
to recruit 200 people from pain centers and primary care to the control group for 
prevalence measurement, patients who have long-term pain, but are not treated with 
opioids. 
As we will have two groups of patients with long-term pain with and without opioid 
treatment, the participants will also be asked separately if they are willing to provide 
blood samples for the examination of biomarkers of pain (O-link panel) as well as 
genetic analysis for future research on effects of opioids and saving samples in the 
biobank. 
 
 
5. Design: 
Testing the COMM psychometric properties, validity and reliability study. 
1) Selection 

Translation and validation of the COMM and ASI-SR – instruments for assessing substance use disorder 
development in a Swedish population of patients with long-term pain treated with opioids 
 
 
200 patients are planned to be recruited in the test group and 200 in the control group. 
Recruitment is planned at: 
- Pain Clinic, University Hospital Uppsala (recruitment manager Lenka Katila) 
- Endometriosis Centre, Uppsala University Hospital (source Mats Olovsson, Christian 
Moberg, recruitment manager Lenka Katila) 
- Primary care Uppsala Region (all primary care centers) (recruitment manager Magnus 
Petersson, Anna Svensson) 
- LARO program for pain patients, University Hospital, Uppsala (recruitment manager 
Lenka Katila) 
The inclusion criteria for the test group are patients with long-term, non-cancer-related 
pain (>3 months) at least 3 days a week, age 18-75 years, who have been treated with 
opioids for at least 1 month and who can speak, read and write in Swedish. 
The inclusion criteria for the control group are patients with long-term, non-cancer-
related pain (>3 months) at least 3 days a week, age 18-75 years, who are not treated 
with opioids (at inclusion and during the last 3 months) and who can speak, read and 
write in Swedish. 
Exclusion criteria are other ongoing diseases or conditions that prevents the patient 
from completing to the study according to the doctor’s assessment, or serious cognitive 
disorder that makes answering the questions impossible. Ongoing or treated cancer in 
the last 10 years. Insufficient knowledge of Swedish is also an exclusion criterion. 
 
Process 
a. Test group 
All patients who have received prescriptions for opioids during the period 2021-2022 
via the respective healthcare providers are identified via extracts from the Cosmic 
medical record system. Excerpts are carried out by the output unit at the IT department, 

Translation and validation of the COMM and ASI-SR – instruments for assessing substance use disorder 
development in a Swedish population of patients with long-term pain treated with opioids 
 
 
region Uppsala, at the request of the responsible researcher and responsible operations 
manager. The researcher responsible for recruitment identifies those who have long-
term pain and LOB (criteria see above). 
Identified patients are contacted by telephone, informed about the study and asked if 
they are interested in participating in the study. Those who respond will be contacted by 
the recruitment officer within 3 weeks. At the same time, the study is advertised at the 
respective receptions in the form of posters in the waiting rooms with the opportunity 
to contact researchers. The doctors working at the respective care facilities can also 
offer patients to participate in the study. 
Those who choose to participate are invited to visit the research nurse or responsible 
researcher for information and to sign informed consent, take samples and submit 
answers digitally. For the part about biomarkers and DNA sampling, a special consent 
will be obtained, thus the patient can participate in the validation without having to 
provide a sample. If necessary, research staff will offer help to filli in the forms digitally 
on site. If possible, the visit is coordinated with any other planned visits to the 
establishment. Samples that will be taken will be: 
 
1. Blood sample for analysis of PETh 
2. Capillary blood from finger for DBS cannabis test 
3. Saliva test for drug and drug screening. 
4. Blood samples for biomarker research and genetic analyses. (if the research subject 
has given separate consent). 
Within 2 weeks after the first visit, the first 100 research subjects may answer the 
COMM and P-GIC forms digitally again (test-retest). 

Translation and validation of the COMM and ASI-SR – instruments for assessing substance use disorder 
development in a Swedish population of patients with long-term pain treated with opioids 
 
 
The research subjects will also be asked in connection with the consent if they would 
like to be interviewed by a researcher. Among the first 30 research subjects who have 
accepted participation in the interviews, they will undergo a semi-structured interview 
(see section Qualitative review). If saturation is reached before 30 participants have 
been interviewed, the number may be lower. 
i. Sample handling 
i. PETh – At least 1ml of venous blood is taken into an EDTA tube with a purple stopper. 
The sample can be stored at room temperature for a maximum of 24 hours. The person 
must not drink alcohol 24 hours before the sample is taken. If transport to the 
laboratory cannot be arranged immediately, it is stored in a refrigerator. Samples are 
ordered in Cosmic with printing of a label used to mark the sample. The sample is sent at 
room temperature to the Academic Laboratory. From the Pain Center and Primary Care 
centers, research personnel personally deliver the sample to the laboratory. Analysis is 
performed by high-resolution liquid mass spectrometry (LC-HRMS), the sample is saved 
for two days and then discarded. 
ii. DBS – Dry blood sample is a capillary blood sample, which is taken from the 3rd or 4th 
finger of the non-dominant hand and 2 drops are collected on a collection card. 
Collection cards are marked with a preprinted study-related barcode. It is transported to 
the Academic Laboratory together with other samples at room temperature. The 
laboratory freezes the sample to -70°C in its biobank and stores these for the analysis. 
DBS is placed in buffer solution and then analyzed with LC-HRMS for 
phosphatidylethanol and cannabinoids. 
iii. Saliva sample – Saliva sample is collected with  standartised sampling kit Quantisal. 
The sample is processed and saved in the biobank at the laboratory. Samples are taken 

Translation and validation of the COMM and ASI-SR – instruments for assessing substance use disorder 
development in a Swedish population of patients with long-term pain treated with opioids 
 
 
for batch analysis after pilot testing, at interim analysis and after collection of all 
samples. 
iv. Blood samples for biomarker analysis for future studies of long-term pain and 
neuroinflammatory processes are handled as follows; Plasma, Tube: 1pc 7/6ml Vacuette 
K2EDTA tube with purple cork (456243) which after centrifugation and aliquoting is 
transported to Ishotellet and DNA analyzes (Tube: 2pc 4ml Vacuette K2EDTA tube with 
purple cork (454410), transported to Uppsala Biobank "Fryshotellet" . 
b. Control group 
Patients who are scheduled for a visit to the pain clinic, pain rehabilitation, 
neuromodulation or GP doctor's visit and are not on opioid treatment are recruited to 
the control group. Pre-screening of this is carried out by responsible recruitment 
personnel. People are contacted by phone by research staff and invited for sampling 
before their visit to the respective facility, and at the same time they are sent 
information about the study for patients. These people sign informed consent at the visit 
and only provide samples for blood, DBS, saliva tests, and possibly biobank samples for 
future analysis of biomarkers and DNA. Only demographic data is collected on these 
individuals, ie age, gender, status, education and employment and confirmation that 
they have a chronic pain condition and are not prescribed opioids. The sampling takes 
place in the same way as the test group. (see i. Sample handling) 
 
c. Form and outcome measure (Answered only by the test group) 
- COMM is based on 17 questions, all of which are answered on a 5-point Likert scale. [4]  
- ASI-SR – (McLellan et al, 1992; Rosen et al ,2000, Ljungvall et al,) – is based on 
interview questions that are used for addiction monitoring by calculating "composite 
scores", mathematical score measures that are sensitive to change and that are used for 

Translation and validation of the COMM and ASI-SR – instruments for assessing substance use disorder 
development in a Swedish population of patients with long-term pain treated with opioids 
 
 
follow-up and research. The scoring measures are produced according to a standardized 
model from the National Board of Health and Welfare (2017). Each domain is calculated 
in point measures. 
In addition to COMM and ASI-SR, the questionnaires BPI-SF, PGI-C, AUDIT and DUDIT 
will be completed electronically or at the first mailing. These correspond to scales for 
characteristics of selected patient groups regarding severity of pain, effect of treatment, 
alcohol and drug use. 
 
- Brief Pain Inventory – short form (BPI-SF) - (Charles C. Cleeland, PhD, Pain research 
Group, Dept. of Neurology, University of Wisconsin Madison and Bengt Bergman: Lund 
division, Sahlgrenska University Hospital, Gothenburg) – measures ongoing intensity 
and impact of pain on different areas of life (eg activity, sleep, well-being). From there 
you can calculate the indexes "Pain Intensity" and "Pain Interference". 
- Patient global impression of change – PGI-C (Geisser et al, 2010). The PGI-C is used to 
measure overall change in health status. The question is directed at whether the patient 
experiences an overall change in health status after starting treatment, in this case 
opioids. 
- Alcohol Use Disorder Identification Test (AUDIT)[41] for alcohol use[41]. 
- Drug Use Disorder Identification Test (DUDIT)[42] for drug use. 
- selected questions from the Pain Disability Index (PDI) which measure disability 
regarding work/study and social role/function.[43] 
- Patient Health questionnaire (PHQ9)[44] 
- Generalized anxiety disorder 7-item scale (GAD-7)[45] 
- Form "Demographic data on research subject" (includes age, gender, education level, 
work status. requested in the survey). 

Translation and validation of the COMM and ASI-SR – instruments for assessing substance use disorder 
development in a Swedish population of patients with long-term pain treated with opioids 
 
 
- Demographic measures: age, sex, level of education, work status is requested in the 
survey, duration of treatment and pain condition and number of visits to healthcare in 
the last six months (specifically acute visits), diagnosis for which the preparation is 
prescribed, preparation and dose and actual amount prescribed in the last 6 months and 
any signs of overuse or problematic use are searched retrospectivly in the Cosmic 
record system by the responsible researcher. 
Validation will be done against the results of drug and alcohol analysis from saliva tests 
and blood. 
As the original COMM instrument has identified 5 categories of questions, each area will 
be assessed against the following instruments: 
1. Symptoms and signs of drug abuse (question 1) – AUDIT, DUDIT, ASI-SR, drug and 
alcohol test 
 2. Emotional and psychiatric problems (questions 2,5,7,8,13) – ASI-SR, GAD-7, PHQ9 
 3. Visitor characteristics/patterns (questions 3,12,17) - medical record data 
4. Occurrence of untrue statement (doubt/lie/untruth) and drug use (questions 
4,6,9,10,11) - medical record data, drug and alcohol tests 
 
5. Medication use and deviation from prescription (non-compliance) (questions 
14,15,16). – medical record data, occurrence of overprescription. 
Pain-related questions will be assessed with the BPI-SF. 
 
d. Qualitative review 
The research subjects will also be asked in connection with the consent if they would 
like to be interviewed by a researcher. Thirty of the first research subjects who answer 
yes will undergo a semi-structured interview where ease of use is examined using the 

Translation and validation of the COMM and ASI-SR – instruments for assessing substance use disorder 
development in a Swedish population of patients with long-term pain treated with opioids 
 
 
"think aloud" method, i.e. questions about what the subjects think about the forms. Main 
issues are understanding of the questions, choice of language and possible associations 
that can be perceived negatively. The interview is then reviewed with qualitative 
content analysis. 
 
e. Expert assessment 
In addition, further evaluation will be carried out where 10 experts in this field in 
Sweden (Pain doctors, addiction medicine doctors, psychologists, behavioral scientists, 
etc.) will be asked to answer questions regarding the assessment of content validity and 
their estimation will be the basis for calculating the Content validity index (CVI). 
6. Sample size 
Bonett's formula has been used to calculate the sample size at a minimum Crohnbach 
alpha index of 0.7 and p= 0.05 and a desired power of at least 80%. The desired number 
for this analysis is 66 people. 
For confirmatory factor analysis with rotation, 170 people are necessary (minimum 10 
per free parameter, n=17) and this was adjusted due to the risk of study dropouts to 200 
people[46]. The final number of people desired to be recruited to achieve relevant 
strength is estimated to be 200. 
For prevalence measurement, the number of positive responses for at least one 
substance is expected to be 10% in the test group and 1% in the control group. To 
achieve alpha 0.05 and beta 0.85, n=114 need to be recruited for an expected result of 
10%, (beta 0.95 n=225, Beta=0.9 n=183). With a calculated risk of 5% drop-out, we will 
include all 200 patients in the test group and 200 in the control group. After collection of 
100 patients, an interim analysis will be carried out to estimate results and if any group 
size needs to be adjusted. 

Translation and validation of the COMM and ASI-SR – instruments for assessing substance use disorder 
development in a Swedish population of patients with long-term pain treated with opioids 
 
 
For test-retest, the first 100 of these patients will be selected from the test group. 
For the qualitative part, an interview with a maximum of 30 patients is planned, 
consecutively among the first to accept participation in this part. If sufficient 
information emerges earlier from the interviews (saturation), the number may be 
smaller. 
 
7. Statistical analysis  
The entire study and the statistical plan are designed in collaboration with statistician 
Anders Berglund from Clinical Neuroscience at KI and Statistics Academy. 
Health data from medical records and data from respective forms as well as laboratory 
responses are compiled in a study database and transferred to the statistics program for 
analysis. Internal consistency and reliability are examined with Cronbach's alpha, which 
is expected to be higher than 0.70 with p£0.05[47]. For analysis of agreement between 
the two test occasions of COMM, intraclass correlation (ICC) will be used. The results 
measured are the total sum of points in COMM. ICC coefficient is judged to be low below 
0.40, satisfactory between 0.40-0.59, good between 0.60-0.70 and excellent between 
0.75-1.00 [48]. 
 Correlation of results of COMM and ASI-SR is assessed with Pearsson and Spearman 
correlation coefficient for the respective clusters of questions. The different 
clusters/dimensions of questions in the form that can be identified to correlate together 
are examined with confirmatory factor analysis with rotation. Discriminant validity of 
ASI-SR composite scores and external validity measures will be calculated with 
intercorrelation matrix between COMM groups of questions, ASI-SR composite scores 
and external validation measures. The limit requirement for charges is >0.40. 

Translation and validation of the COMM and ASI-SR – instruments for assessing substance use disorder 
development in a Swedish population of patients with long-term pain treated with opioids 
 
 
SPSS, SAP and Amos programs are used for statistical processing. The qualitative part is 
not covered by the statistical plan. 
In prevalence estimation, both groups will be described with descriptive statistics. 
Occurrence of addictive drugs and drugs as well as measures of alcohol use (PETh) 
during the last 3 weeks in both the test group and the control group will be compared 
with a chi2 test. Odds analysis of secondary use of illegal substances, parallel 
dependence on other substances and drugs and alcohol during LOB is carried out. 
Correlation analysis of PETh results from standard blood tests and DBS is carried out. 
 
8. Timetable 
Recruitment will start in the december of 2023. Collection of data and samples is 
estimated to last for at least one year until the required number of research subjects is 
recruited, estimated to take 24 months, but a maximum of 36 months. Processing of data 
and compiling results and script is estimated to begin in 2025. Completion of study is 
estimated to 31.12. 2025, but may be extended depending on the pace of recruitment. 
Publication is planned for 2026-7. 
 
9. Relevance to the society 
Treatment with opioids for long-term non-cancer-related pain should only take place in 
carefully selected patients, where the risk of addiction development is low and even 
then, the treatment must be monitored. Identification of the risk of addiction before 
starting treatment is important, as well as follow-up with the identification of early signs 
of addiction. Currently, there is no validated Swedish instrument that identifies 
addiction problems in patients with pain and ongoing opioid treatment. COMM is 

Translation and validation of the COMM and ASI-SR – instruments for assessing substance use disorder 
development in a Swedish population of patients with long-term pain treated with opioids 
 
 
developed specifically for this group and thus has the potential to facilitate assessment 
and follow-up of patients. The ASI-SR is validated for the addiction population, but not 
for pain patients. Routine urine drug screening is a problem for most healthcare 
facilities in Sweden. Introduction of new analytical methods with high specificity and 
sensitivity but at the same time low costs and easy handling is important in securing 
patients' health. Knowledge of the prevalence of substance use in Sweden is important 
both in the national health economic considerations, when introducing and designing 
clinical routines and assessment of the individual care recipient. 
 
10. Ethical aspects 
 
The subject's data will be pseudonymized and saved with a special study code, which 
only the study doctor has access to on the Pain Centre's research database. Results will 
be presented at group level and no data on patient identity will be presented in 
publications. The sampling does not deviate from usual clinical sampling. Test results 
from PETh will be able to be used in clinical assessment, which is still part of usual 
clinical consideration. Answers to drug samples will not be available in clinical practice, 
moreover, samples are analyzed long after the  clinical visit. The patient need not fear 
that the result will affect the doctor's assessment and treatment. Samples are destroyed 
if the patient requests this or after the study is completed, except for the samples for 
analyzes of neurobiological markers in opioid use, which will be saved in the biobank for 
15 years. 
In conclusion, the benefit of the information, which may contribute to improved care of 
this patient population, exceeds the potential risks to which the research subject may be 
exposed. 

Translation and validation of the COMM and ASI-SR – instruments for assessing substance use disorder 
development in a Swedish population of patients with long-term pain treated with opioids 
 
 
 
11. Data processing 
All data will be handled confidentially in accordance with the Data Protection Regulation 
(GDPR) Article 6 and stored in an encrypted folder on the Pain Clinic's server in the 
manner and for the time required by the regulations. Data is processed using statistical 
software by professional statistician. Data undergoing statistical processing is coded. 
Study data will be stored for 15 years. 
 
12. Funding: 
The Pain Centre Uppsala University Hospital is the main financier (partly clinical funds 
but also Research and development funds of Region) with contributions from  Kamprad 
Family Research Grant, Uppsala University, Department of Surgical Sciences, 
Department of Neurosciences, Department of Public Health and Care Sciences, General 
Medicine and Preventive Medicine, Primary Care, Region Uppsala and the Academic 
Laboratory in the form of salary to participating researchers. The academic laboratory is 
responsible for the costs for storage of samples at the laboratory and analyzes of DBS 
samples. Projects have so far been granted SEK 3,640,000 from R&D funds.  
 
13. Distribution of responsibilities 
Rolf Karlsten, senior consultant, associate professor and section manager for the Pain 
Center is the Principal Investigator for the implementation of the entire project, 
responsible for financing and oversees all parts of the project. 
Lenka Katila, consultant in pain medoicine and PhD student in the project. Lenka has 
clinical links to the Pain Centre, the Addiction Clinic and the Endometriosis Centre. She 

Translation and validation of the COMM and ASI-SR – instruments for assessing substance use disorder 
development in a Swedish population of patients with long-term pain treated with opioids 
 
 
is coordinating researcher and is responsible for translation and the validation process, 
EPN application, recruitment within specialist care at Academic hospital, statistical 
analysis, coordinator of the qualitative part and coordination of publications and 
dissemination of the results to the public and professions. 
Hanna Ljungvall is a sociologist and doctor of medicine. She is participating in discussion 
about project design, translation, responsible for qualitative interviews and its 
qualitative analysis. 
Pernilla Åsenlöf is a physiotherapist at the pain center and professor in physiotherapy. 
She has an advisory function and review regarding the translation and validation 
process. Her great knowledge in qualitative research is of great importance in the parts 
where qualitative methods and analysis are carried out. Important role in the 
preparation of manuscripts and in the publication process. 
Annica Rhodin, doctor and doctor of medicine, is an expert researcher in drug addiction 
and participation in the translation and is an advisor in the entire process. 
Anna Svensson, general practitioner and PhD student is responsible for the recruitment 
process in primary care and participation in qualitative interviews. 
Magnus Peterson is a general practitioner, pain consultant participating in the 
discussion about project design with overall responsibility for recruitment in primary 
care. 
Anders Berglund, Doctor of Philosophy, is participating in the discussion about the 
design of the project and is responsible for the statistical plan and analysis. 
Torbjörn Åkerfeldt, is a senior physician and medical management manager at the 
Academic Laboratory with long-term experience in drug and drug analysis and a 
doctoral student at the Department of Medical Research. Participates both in planning 
and practical implementation of study as well as evaluation of results. 

Translation and validation of the COMM and ASI-SR – instruments for assessing substance use disorder 
development in a Swedish population of patients with long-term pain treated with opioids 
 
 
Kim Kultima is associate professor in the Department of Medical Science and biomedical 
analyst with expertise in applied biomedical analyses. Responsible for carrying out 
analyses, checking results and their interpretation. 
Rezvan Kiani Dehkordi – research nurse at the Pain Centre, responsible for 
documentation, sample handling procedures and GCRP 
 
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