Clinical Study of TripleA Connected to Diagnosis, Care and Aftercare of Alcohol Addiction in Outpatient Care
Phase: NA
Conditions: Alcoholism
Sponsor: Kontigo Care AB

                                                 
 
 
Title 
      
TripleA-enhanced aftercare after basic treatment of 
alcohol dependence in outpatient care  
Protocol number 
 
KC102-001 
NCT number 
 
NCT03195894 
      
      
Revision 
      
V1.0 
Project 
      
N/A 
Issued by 
      
Elin Karlberg 
Date 
      
20150626 
 
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TripleA-enhanced aftercare after basic treatment of alcohol dependence in outpatient care  
 
 
 
 
Kontigo Care 
 
Clinical Study Protocol 
 
TripleA-enhanced aftercare after basic treatment of  
alcohol dependence in outpatient care  
 
 
 
 
KC102-001 
 
 
 
 
 
 
Author 
Elin Karlberg 
Signature 
Date 
2015-06-26 
Reviewed by 
Christina Nehlin Gordh 
Signature 
 
Date 
2015-06-26 
Approved by 
Markku Hämäläinen 
Signature 
 
Date 
2015-06-26 

 
 
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TripleA-enhanced aftercare after basic treatment of alcohol dependence in outpatient care 
Revision history summarized (if protocol changes are done) 
Not applicable for the first version of the protcol. 
Sponsor 
Kontigo Care AB, Box 11008, 75011 Uppsala 
Besöksadress: Dragarbrunnsgatan 35, Uppsala) 
Contact person:  
Research Director Markku Hämäläinen, PhD  
 
 
markku.hamalainen@kontigocare.com 
 
 
Tel: 0769 47 31 32 
 
Project Management 
Innovation Akademiska,  
Akademiska sjukhuset,  
751 85 Uppsala 
Contact person: 
Project Manager Elin Karlberg 
 
 
elin.karlberg@akademiska.se 
 
 
Tel 018-611 13 66, 073-868 22 59 
Principal Investigator, Coordinating Investigator and Study sites 
 
Principal Investigator 
Tobias Eriksson, chief physician 
Addiction and neuropsychiatry, University Hospital, 751 85 Uppsala 
 
Medical monitor 
 
Christina Nehlin Gordh, MD, socionom,  
Department of Neuroscience, Uppsala University 
Affective disorders, Univerity Hospital, 751 85 Uppsala 
 
Study site 
Addiction medical clinic, University Hospital, 751 85 Uppsala 
 
Other institutions/units involved in the clinical study 
Laboratory analyses:  
Academic laboratory 
Clinical chemistry and pharmacology 
University Hospital 
751 85 Uppsala 
Subcontractor for PEth analyses: 
Karolinska University Hospital, Huddinge 
Clnical Pharmacology, The Addiction Laboratory 
141 86 Stockholm 
 

 
 
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TripleA-enhanced aftercare after basic treatment of alcohol dependence in outpatient care 
INNEHÅLLSFÖRTECKNING 
 
Sponsor ................................................................................................................................................... 2 
Project Management ............................................................................................................................... 2 
Principal Investigator, Coordinating Investigator and Study sites ........................................................... 2 
Other institutions/units involved in the clinical study ........................................................................... 2 
1. Summary ...................................................................................................................................... 5 
2. Introduction ................................................................................................................................... 8 
3. The alcohol program at the Academic Hospital ............................................................................ 9 
3.1. 
The three phases of the alcohol program ............................................................................. 9 
3.2. 
Conventional treatment at the addiction medicine clinic ..................................................... 10 
4. Identification and description of the test product ........................................................................ 12 
4.1. 
TripleA ................................................................................................................................. 12 
4.2. 
Manufacturer ....................................................................................................................... 13 
4.3. 
Product identification ........................................................................................................... 13 
4.4. 
Traceability .......................................................................................................................... 13 
4.5. 
Intended use ........................................................................................................................ 13 
4.6. 
Composition of the test product .......................................................................................... 13 
4.7. 
Evaluation of the results of the relevant preclinical tests/assessments 
performed to justify the use of the test product in human subjects ............................................... 14 
4.8. 
Evaluation of clinical data relevant to the current clinical study .......................................... 14 
5. Risks and benefits of the test product and the clinical study ...................................................... 14 
5.1. 
Expected clinical benefits .................................................................................................... 14 
5.2. 
Expected side effects from the test product ........................................................................ 15 
5.3. 
Remaining risks associated with the test product ............................................................... 15 
5.4. 
Risks associated with participation in the study .................................................................. 15 
5.5. 
Interactions .......................................................................................................................... 15 
5.6. 
Risk reduction measures ..................................................................................................... 15 
5.7. 
Risk-benefit motivation ........................................................................................................ 15 
6. The study´s objectives and hypotheses ..................................................................................... 16 
6.1. 
Objectives ............................................................................................................................ 16 
6.2. 
Hypotheses ......................................................................................................................... 16 
6.3. 
Claims and performance to be verified ............................................................................... 16 
6.4. 
Risks and adverse effects ................................................................................................... 16 
7. Study design ............................................................................................................................... 17 
7.1. 
Generally ............................................................................................................................. 17 
7.2. 
Efficacy endpoints ............................................................................................................... 18 
7.3. 
Methods and times for measuring, registering and analyzing variables ............................. 20 
7.4. 
Equipment to be used in the clinical study to meaasure variables ..................................... 26 
7.5. 
Loss ..................................................................................................................................... 26 
7.6. 
Test product(s) and comparator(s) ...................................................................................... 26 
7.7. 
Subjects ............................................................................................................................... 27 
7.8. 
Procedures .......................................................................................................................... 28 
8. Monitoring plan ........................................................................................................................... 33 
9. Statistical considerations ............................................................................................................ 34 
9.1. 
Statistical design, method and analysis procedure ............................................................. 34 
9.2. 
Sample size, significance level and statistical strength ...................................................... 37 
9.3. 
Interim analysis ................................................................................................................... 38 
10. Data management .................................................................................................................... 38 
11. Changes to the study protocol .................................................................................................. 38 
12. Deviations from the study protocol ........................................................................................... 39 
13. Responsibility for the test products ........................................................................................... 39 
14. Compliance with laws, guidelines and standards ..................................................................... 39 

 
 
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15. Insurance .................................................................................................................................. 40 
16. Informed consent ...................................................................................................................... 40 
17. Safety reporting ......................................................................................................................... 40 
17.1. 
Definitions .......................................................................................................................... 40 
17.1.1. Adverser Event (AE) ....................................................................................................... 40 
17.1.2. Adverse Device Effect (ADE) .......................................................................................... 40 
17.1.3. Device deficiency ............................................................................................................ 40 
17.1.4. Serious Adverse Device Effect (SADE) .......................................................................... 41 
17.1.5. Serious Adverser Event (SAE) ........................................................................................ 41 
17.1.6. Unanticipated Serious Adverse Device Effect (USADE) ................................................ 41 
17.2. 
Time frames for reporting .................................................................................................. 42 
17.3. 
Content of the report ......................................................................................................... 43 
17.4. 
Malfunction reporting ......................................................................................................... 44 
17.5. 
Expected adverse medical events .................................................................................... 44 
17.6. 
Contact information for reporting ....................................................................................... 44 
17.7. 
Data Monitoring Committe................................................................................................. 45 
18. Exposed/extra vulnerable population ........................................................................................ 45 
19. Interruption or premature termination of the clinical trial .......................................................... 45 
20. Interview study .......................................................................................................................... 45 
21. Publication policy ...................................................................................................................... 46 
22. References ................................................................................................................................ 46 
Appendix A .................................................................................................................................... 48 
Appendix B .................................................................................................................................... 50 
Bilaga C ......................................................................................................................................... 52 
Bilaga D ......................................................................................................................................... 53 
Bilaga E ......................................................................................................................................... 54 
Bilaga F ......................................................................................................................................... 56 
Bilaga G ......................................................................................................................................... 57 
 
 

 
 
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TripleA-enhanced aftercare after basic treatment of alcohol dependence in outpatient care 
1. Summary 
 
TripleA-enhanced aftercare after basic treatment of  
alcohol dependence in outpatient care  
KC102-001 
Study design  
 A randomized, controlled, open-label study 
comparing conventional therapy with and without 
enhancement of TripleA. 
 
Length (intervention and  follow up period)  
12 months 
Investigational product 
The TripleA product consists of an alcohol meter 
that is connected to a mobile app that is installed 
on a mobile phone, as well as caregiver portal. 
Interventional arm 
 
TripleA - a medical technology system that can 
frequently and space-boundly measure whether 
a person has drunk alcohol - in addition to 
conventional treatment. 
 
Control arm 
Conventional treatment (without addition of 
Triple A)  
Study population  
Adults with alcohol dependence. The clinical 
study intends to frequently and place-bound, 
through several measurements per day, monitor 
sobriety for patients in outpatient care and 
aftercare during alcohol treatment. The 
population refers to patients undergoing 
conventional outpatient treatment with 
medication (eg disulfiram [Antabus], 
acamprosate [Campral], naltrexone [Naltrexone 
Vitaflo] and nalmefene [Selincro]) and / or with 
various therapies (CBT, MI call, 12- step 
treatment). 
 
Number of subjects 
106 randomised patients, distributed 1:1 
between test arm and control arm 
Inclusion criteria 
 
Patients for whom there is a care 
commitment for the alcohol program at 
the Addiction and Neuropsychiatry, 
Uppsala University Hospital 
 
 
18 years or older 
 
Meets at least 2 of the criteria for 
addiction / substance syndrome 
according to DSM-5 
 
Ability to undestand and communicate in 
Swedish 

 
 
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TripleA-enhanced aftercare after basic treatment of alcohol dependence in outpatient care 
 
Ability to handle the technical equipment 
used in the study (breathalyzer + 
smartphone)  
 
Has a fixed point (accommodation, night 
rest place with possibility to charge the 
phone) 
 
Exclusion citeria 
 
Schizophrenia 
 
Substance syndrome related to 
substances other than alcohol and 
nicotin 
 
Impaired lung function (not able to 
achieve adequate exhalation volume for 
breathalyzer function) 
 
The patient is cared for within the 
framework of LVM 
 
Unsuitable to participate in the study 
according to the examiner's assessment 
 
Has not consumed any alcohol during 
the 4 weeks that baseline Time Line 
Follow Back refers to. 
 
Normalized  CDT and PEth-values in 
blood samples collected at visit 1.  
Study Objectives 
Primary objective 
The primary objective of the study is to 
investigate differences in alcohol consumption 
patterns between alcohol dependents who 
receive only conventional treatment and alcohol 
dependents who receive conventional treatment 
enhanced with TripleA. 
Secondary objectives 
 
Investigate whether more patients 
can achieve and maintain sobriety if 
conventional treatment is enhanced 
with TripleA 
 
Investigate whether TripleA can help 
reduce the number of relapses and 
whether the relapses may be 
delayed 
 
Investigate whether TripleA can help 
fewer patients discontinue treatment 
 
Collect data on health outcomes as 
a basis for health economic analyzes 
 
To use interviews to evaluate how 
users experience the product TripleA 
in different respects 
 
 

 
 
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TripleA-enhanced aftercare after basic treatment of alcohol dependence in outpatient care 
Outcomes 
Primary Outcome 
Difference between the treatment arms in 
proportion of patients with no heavy drinking 
days during the 4-weeks period before the 12 
months follow-up visit. 
Secondary Outcomes 
Difference in proportion of sober patients during 
the four weeks period before the 6 and 12 
months visit, respectively. 
Difference in total amount consumed alcohol per 
4 weeks period before  6 and 12 months visit, 
respectively, compared to baseline. 
Difference in number of heavy drinking days per 
4 weeks period before 6 and 12 months visit, 
respectively, compared to baseline. 
Difference in number of sober days per 4 weeks 
period before 6 and 12 months visit, 
respectively, compared to baseline. 
Difference in number of standard glasses per 
drinking day during the four weeks period before 
the 6 and 12 months visit, respectively. 
Time to relapse 
Clinical Global Impression improvement after 6 
and 12 months, respectively. 
Change in health outcome measured with EQ5D 
Proportion of patients who have reduced their 
AUDIT score after 12 months. 
Proportion of patients who have reduced their 
AUDIT score with at least one zone. 
Proportion of patients having a risk level <II (i.e. 
less than 6 AUDIT points for women, 8 AUDIT 
points for men) after 12 months.  
Change in degree of alcohol dependence 
measured as the difference in SADD-points at 
12 and  6 months respectively, compared to 
baseline.  
Compliance with agreed treatment. 
Change in the presence of the alcohol 
metabolites PEth and CDT in the blood at 6 and 
12 months respectively compared to baseline. 
 
 

 
 
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TripleA-enhanced aftercare after basic treatment of alcohol dependence in outpatient care 
2. Introduction 
 
Problematic Alcohol consumption 
 
The WHO's Global Status Report on Alcohol and Health 2014 contains comprehensive statistics 
on alcohol consumption from 2010. It shows that the part of the world's population that was 15 
years or older in 2010 consumed 6.2 liters of pure alcohol per person, which corresponds to 13.5 
grams per person and day. Many people do not drink alcohol at all, but of those who drink and are 
15 years or older, 16% globally, almost 23% in Europe and as much as 34.5% in Sweden, 
regularly drink heavily, i.e. drink 60g of alcohol or more at one and the same time at least once a 
month. 
The prevalence of alcohol dependence is stated in the WHO report to be 4.7% of the population in 
Sweden (15 years or older), which is higher than the European average. If you combine harmful 
use and dependence, the figure is 8.9%. 
There are several different terms and definitions of having a problematic relationship with alcohol 
and other drugs. The terms used also have different meanings depending on the business and 
occupational group. 
In the medical field, the terms are mainly linked to the diagnostic classifications used. In Sweden, 
ICD-10 is mainly used in the diagnosis of diseases in the health care system. DSM is used in 
research and to some extent in psychiatric activities. Until recently, the DSM-IV was used which 
distinguished between alcohol dependence and abuse. In the latest version of DSM, DSM-5, 
however, there has been talk of substance abuse syndrome. Substance syndrome is a 
combination of the two previous concepts of addiction and substance abuse. For diagnosis, at 
least two criteria must be met. The degree of difficulty is stated as “mild” if 2–3 criteria are met, as 
“moderate” if 4–5 criteria are met, and as “severe” if more than 5 criteria are met. 
Heavy drinking has many negative consequences and is one of the leading causes of premature 
death and illness in Europe. The costs of this, which can be linked to health care, drunk driving, 
unemployment, absenteeism from work, reduced productivity of those who work despite drinking, 
premature mortality and the harm to people in the environment, are enormous. The most recent 
estimate of Swedish annual costs was made in 2002 and the estimated amount was then close to 
SEK 30 billion (Johansson 2006). 
 
Treatment goals 
 
The goal of the treatment of alcohol dependence used to be almost always complete sobriety, but 
in recent decades the idea of controlled drinking where one achieves a significant risk reduction 
without total abstinence has gained ground. Controlled drinking can be a way of accepting 
treatment for one's alcohol dependence even if one is not prepared to give up completely, and can 
significantly reduce the physical and psychosocial consequences of alcohol use. However, it is not 
uncommon during the course of treatment to need to re-evaluate the goal when the patient 
realizes that he or she is unable to control drinking, and then may become more motivated to try 
to stay completely sober instead. There are results that indicate that regardless of whether the 
goal of treatment is risk reduction via controlled drinking or complete sobriety, you get equivalent 
outcomes. However, the fact that patients themselves can be involved in choosing their treatment 
goal increases the possibility that the treatment will be successful. (van Amsterdam and van den 
Brink, 2013). 

 
 
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TripleA-enhanced aftercare after basic treatment of alcohol dependence in outpatient care 
 
A new product to enhance the treatment 
TripleA is a new product based on measuring alcohol in the exhaled air place-bound, discreetly 
and frequently (several times a day). Measurement of alcohol (ethanol) in breath tests is an 
established method for detecting or dismissing the influence of alcohol, for example in connection 
with sobriety checks in traffic and in alcohol locks. Exhalation tests are also used in healthcare, 
prison care and in working life. TripleA conveys information about the results of the alcohol 
measurements to the patient's regular care contact. The idea with the product TripleA is that it 
should function as a complement to the treatment regardless of the goal and type of treatment. 
 
Two separate clinical trials are being conducted to evaluate the product in two different contexts: 
KC102-001 and KC102-002. Both studies are briefly described in the following sections. This 
study protocol then describes the implementation of KC102-001. 
 
KC102-001 – Clinical study of TripleA in diagnosis, care and aftercare of alcohol 
dependence in outpatient care  
The study KC102-001 is carried out in connection with outpatient care at the Academic Hospital's 
Addiction Clinic. It is possible here to introduce the product already during the assessment phase, 
when information is gathered and an assessment is made of what treatment the patient needs. 
TripleA can be continued (or initiated) even during the treatment phase as patients have close 
contacts with their therapist and often also start drug treatment. Drug treatment can be alone or in 
combination with other therapy which can be motivational conversations, cognitive behavioral 
therapy, etc. Exhalation and blood sampling are common. Biofeedback, which means that you 
return the test results to the patient and can link changes in drinking patterns to changes in the 
result when taking samples, is a way to make the patient aware and interested in how alcohol 
affects the body. The patient can see in black and white that reduced alcohol consumption has 
improved health. 
 
When the primary treatment is completed and switched to follow-up / aftercare with sparse 
recurrences, TripleA continues to support the patient and maintains contact with the caregiver. At 
Akademiska sjukhuset, both complete sobriety and risk reduction through controlled drinking are 
used as treatment goals, which is adapted individually for each patient. 
 
KC102-002 – Clinical study of TripleA-enhanced aftercare after basic treatment of 
alcohol dependence in treatment homes 
The study KC102-002 is carried out in connection with inpatient care at Nämndemansgården's 
treatment home. Nämndemansgården's operations use the 12-step program. After at least one 
month of intensive treatment in a boarding school, the patients switch to aftercare activities that 
involve meetings every week or month. The 12-step program aims for complete sobriety. 
Aftercare involves more frequent follow-up compared with the University Hospital's model, but no 
samples are taken and no medication is prescribed. Patients are provided with TripleA before 
leaving the treatment home or at the first aftercare. 
3. The alcohol program at the Academic Hospital 
3.1. 
The three phases of the alcohol program 
Patients are welcome to contact the addiction clinic for advice and / or self-report. Patients are also 
admitted on referral from somatic care, other psychiatry, primary care and other actors such as the 
prison service, social services, student health and occupational health care. All referrals are 
assessed via an outpatient round. The staff group consists of a team with different professions to 
ensure adequate care where both medical and psychosocial factors are taken into account. 

 
 
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The efforts of the alcohol program are divided into three different phases: the way in, the way 
through and the way forward. 
In the first phase - the way in - the focus is on assessment and investigation. The first phase ends 
with the patient receiving an oral and written summary of what has emerged during the assessment 
interviews. 
If the patient then chooses to proceed, phase two begins - the way through. Here, the patient, 
together with their therapist, will weigh the advantages and disadvantages of a change and make a 
plan for how the change will take place and which treatment options suit the individual. The 
treatment is evaluated continuously and at follow-up meetings after the end of treatment. 
In the last phase - the way forward - there is either a conclusion or an in-depth assessment based 
on social complications, somatic complications, psychiatric comorbidity and / or resource level. The 
results provide guidance on whether the patient should be referred to another instance or whether 
other interventions may be relevant within the framework of the alcohol program. 
 
Within the alcohol program, drugs are combined with methods such as relapse prevention with 
motivational conversations. Within the framework of the current study, all study participants will 
undergo some form of conventional treatment, i.e. any or a combination of the following treatment 
methods. The intervention group will also have access to TripleA. The description of the 
conventional treatment methods in section 3.2 below is taken from the Clinical Handbook 2014 
Alcohol - Risk use, addiction and dependence, Alcohol syndrome A decision support in the 
investigation and treatment of Tobias Eriksson, Chief Physician Addiction & Neuropsychiatry, 
Academic Hospital. 
3.2. 
Conventional treatment at the addiction medicine clinic 
3.2.1. Relapse prevention 
Relapse prevention has its origins in cognitive behavioral therapy (CBT), which is about re-learning 
and reorientation based on the mapping of dysfunctional thoughts and behaviors. 
You can individually or in groups, among other things, handle cravings, say no to alcohol, plan for 
emergencies and handle incipient relapses. You get to learn about the brain's reward system and 
problem solving. The concept of post-acute abstinence is highlighted, where the imbalance in the 
reward system gives different symptoms long after acute symptoms have subsided. 
The treatment is usually carried out during eight sessions, each of which takes approximately 45-
90 minutes, depending on whether it is individual or in a group. Between the sessions, the 
participant is given homework that translates theory into practice and provides tools for dealing with 
everyday life. 
3.2.2. 
Motivating conversation  
 
Here, the treatment is focused on the patient's own will for change, which requires a lot of 
motivation as you have to bring about a change in habits that have been around for a long time. 
 
The therapist in motivational conversation therapy is neutral during the sessions and does not 
describe what is good to do, but should instead help to get the patient to express arguments for 
and against drug consumption and then make their own decisions that lead to change in the 
right direction. 
 
This is a treatment model that suits risk users and those with more limited problems. 
 
3.2.3. 
Drug treatment 

 
 
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Acamprosate (drug name Campral, Aotal) inhibits the effect of excitatory neurotransmitters in the 
brain. The drug prevents the increase of glutamate extracellularly in the brain in connection with 
alcohol withdrawal and the reward system is favorably affected. Tablets of 333mg are dosed 2 + 2 
+ 2 at body weight over 60kg and 2+ 2 if the body weight is below 60kg. The drug reduces the 
positive experience of alcohol and prolongs the time to alcohol consumption or relapse. 
Naltrexone is an opiate receptor antagonist and reduces the effect of the endorphins released during 
alcohol intake, this affects the reward system which clinically manifests itself as reduced cravings, 
and increases the number of non-alcoholic days. 50mg tablets are dosed once daily. 
 
Nalmefen (drug name Selincro) is an opioid system modulator with effect on my, delta and kappa 
receptor. Due to rapid uptake works in need procedure. 
The drug affects the brain's motivational system with the end result of reducing the desire for alcohol 
intake and avoiding loss of control. 
 
The preparation has the indication reduction of alcohol consumption and may be relevant in the 
treatment of risk consumption where the desire is a reduction rather than completely stopping 
consuming alcohol. 18 mg tablets are taken 1x1 if needed. The patient should take the preparation 
before any alcohol consumption, preferably the drug should be taken 1-2 hours before presumed 
consumption but can have an effect even if you take it when you start drinking. You should not take 
more than one tablet per day. 
 
Disulfiram (Antabus) is an old, well-proven aversion drug based on the principle that it should be so 
unpleasant to drink alcohol that one refrains. 
Alcohol is broken down in the body via two steps where the latter means that acetaldehyde 
becomes acetic acid and water with the help of the enzyme aldehyde dehydrogenase. This 
enzyme is blocked by disulfiram and an accumulation of acetaldehyde when consuming alcohol 
causes symptoms in the form of flatulence, flushing, palpitations, throbbing headache, nausea 
and vomiting. Antabus is an excellent preparation for motivated individuals and the best evidence 
can be noted when it is given supervised. Tablets of 400mg are taken three times a week, in case 
of side effects you can prescribe 200mg daily. Should be supervised if possible. 

 
 
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4. Identification and description of the test product 
4.1. 
TripleA 
The TripleA system consists of an alcohol meter, an app, a caregiver 
portal and a database. The care recipient uses the alcohol meter and 
the associated app for sobriety tests and in some cases for registration 
of meetings. Sobriety tests and meeting participation are controlled from 
the caregiver portal. All information is handled in accordance with the 
Personal Data Act. The care provider delivers TripleA to the care 
recipient. TripleA can be used immediately. 
Alcohol meter  
The alcohol meter measures and analyzes alcohol in the exhaled air. 
The information is transmitted wirelessly to the app. 
Application 
A message from the caregiver portal urges the user to take a sobriety test..  
The user opens the app and starts the alcohol meter, after which the devices ate 
connected via Bluetooth. 
The user starts a sobriety test using the app and does a breath test. During sampling, 
a photo is taken to ensure the correct identity of the sampler. The test result is 
displayed in the caregiver portal for the caregiver. In the app, you can also check in 
for meetings by registering the GPS coordinates for the meeting you visit.  
 
Database 
 
The database stores all information regarding sobriety testsm photis 
and reigsterd meetings. All data is stored securely in accordance with 
the Personal Data Act.  
 
Caregiver portal 
In the caregiver portal, the caregiver registers his patients and can 
create an inividual plan for sobriety tests and meeting participation..  
Via the caregiver portal, the caregiver can check the results from 
sobriety tests and meeting participation as well as personal 
identification.  
 
                  
 
 
 
 

 
 
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4.2. 
Manufacturer 
Kontigo Care AB, Box 11008, 750 11 Uppsala.  
Visiting address: Dragarbrunnsgatan 35, Uppsala. 
4.3. 
Product identification 
TripleA 1.0. 
TripleA is a CE-marked medical device and meets the requirements of the Medical Products 
Agency's regulations LVFS 2003: 11 .. TripleA has been developed in accordance with the 
European Medical Directive 93/42 / eec. TripleA is developed for professional use and meets 
applicable requirements for accuracy in accordance with SS-EN 15964: 2011. 
TripleA is classified as a Class I product according to rules 5 and 12 of MEDDEV 2.4 / 1. The product 
has a measuring function but does not fully meet the criteria for class Im according to MEDDEV  
2.1 / 5.  
4.4. 
Traceability 
Each alcohol meter has a unique serial number and is paired with a specific mobile phone with 
associated app. The information is stored in Kontigo Care's database. Via the care provider portal, 
it is registered which meter has been distributed to which study patient, which ensures traceability 
and the possibility of delivering a new unit to the patient when it is time for calibration or if a unit 
needs to be replaced due to a malfunction. Only staff authorized by Kontigo Care have access to 
patients' personal data and a secure login is required to view data. Unauthorized staff at Kontigo 
Care cannot see a patient's personal information  
. 
4.5. 
Intended use 
TripleA is intended for medical use by caregivers and patients in the treatment of alcohol 
dependence. TripleA is a complement to other methods available to the caregiver to control patients' 
sobriety and compliance with therapy over time and to motivate patients to maintain sobriety. The 
product consists of an alcohol meter for exhaled air controlled via an app, a web-based care provider 
portal for handling patients and a database for collecting and storing information and measurement 
data. 
TripleA is intended for use by patients for: 
Frequent and site-bound sobriety measurement. 
• Registration of participation in planned treatment meetings such as AA meetings. 
 
TripleA is intended to be used by caregivers for: 
• Supervision and control of sobriety measurements and meeting participation. 
• Evaluation of measurement results and management of the outcome of patients' compliance with 
therapy. 
4.6. 
Composition of the test product 
The test product TripleA consists of an alcohol meter, a mobile phone with an installed app, a micro-
USB charger, instructions for use and extra blow nozzles. The blowing nozzle that will be placed in 
the user's mouth is made of a biocompatible plastic material (Cycoloy HC1204HF-8H5D003). 

 
 
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Ethyl glucuronide (EtG) and ethyl sulfate (EtS) are conjugated ethanol metabolites that are 
commonly measured in urine samples but can also be measured in blood and hair samples. EtG 
and EtS in urine are used as markers to detect alcohol consumption or confirm sobriety during the 
last 24 hours. A minor to moderate alcohol intake can be detected for up to 1 day and intoxication 
for up to a couple of days afterwards. EtG and EtS are eliminated more slowly than ethanol and 
therefore they can be used even after the ethanol has disappeared from the body. (Helander 2011).  
Phosphatidylethanol (PEth) is a group of membrane lipids formed from phosphatidylcholine in the 
presence of ethanol and measured in whole blood. PEth is used as a marker to demonstrate regular 
alcohol consumption and "risk use" or to confirm sobriety in recent weeks (Helander 2011). PEth is 
specific for alcohol, but does not detect occasional intoxication. The half-life is 4-7 days (Helander 
2011, Helander et al 2012). The concentration of PEth-16: 0/18: 1 in the blood reflects the alcohol 
consumption of recent weeks. PEth-16: 0/18: 1 values lower than 0.05 µmol / L indicate no or low 
sporadic alcohol consumption. Values between 0.05-0.30 µmol / L speak for regular moderate 
consumption, but even occasional very large intakes of alcohol can probably give measured values 
in this range. (Sampling instructions B-Phosphatidylethanol, Karolinska University Laboratory). 
Low carbohydrate transferrin (CDT) shows alcohol-induced change in the glycosylation pattern of 
transferrin, which is measured in serum samples. CDT is used as a marker to demonstrate regular 
alcohol consumption and «risk use / abuse«, where the measured value reflects the intake during 
the last weeks - the month. Single major alcohol intakes do not affect CDT levels. The specificity is 
controversial, as an elevated CDT value may have causes other than alcohol. 
Within the framework of the current study, PEth and CDT will be analyzed. 
4.7. 
Evaluation of the results of the relevant preclinical tests/assessments 
performed to justify the use of the test product in human subjects 
The product meets the essential requirements according to the Medical Products Agency's 
regulations for medical devices, LVFS 2003: 11. The product has undergone the required safety 
tests and meets the requirements of the European standards IEC 60601-1 and 60601-11. Product 
documentation can be found in the technical file that forms the basis for the CE marking of the 
product. Electrical safety and EMC have been tested by Intertek. 
4.8. 
Evaluation of clinical data relevant to the current clinical study 
Prior to the CE marking of the product, a review of clinical data regarding safety and performance 
for TripleA and similar products is compiled in the Clinical Evaluation Report. In summary, there is 
limited data for equivalent products, as TripleA is a system with several components. There is 
dock data that supports each component itself is secure and has effects and features that can 
contribute to the composite system. 
 
5. Risks and benefits of the test product and the clinical study 
5.1. 
Expected clinical benefits 
TripleA is expected to support the patient in his decision to reduce or completely abstain from 
alcohol consumption, by reducing the space where one can otherwise drink without anyone else 
finding out. Via TripleA, the therapist and patient also receive more reliable data on the patient's 
alcohol intake patterns and can, based on this, find strategies for managing risk situations. TripleA 
also means that any relapses can be noticed more quickly and further treatment can be initiated if 
necessary. 

 
 
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TripleA-enhanced aftercare after basic treatment of alcohol dependence in outpatient care 
 
5.2. 
Expected side effects from the test product 
 
The use of TripleA entails a significant restriction on the patient's privacy as information about 
alcohol intake is communicated to the care provider. However, this is one of the main points of the 
method and a prerequisite for the use of TripleA both within the framework of the current study 
and addiction care in general is that it is voluntary for the patient to use TripleA as enhanced 
support for other interventions. 
Probably even a sober patient experiences a strong stress if you do not have the opportunity to 
perform a prescribed sobriety test within a given time, or discover that you have missed a test. How 
this is experienced will be mapped in focus group interviews. The patient is also given the 
opportunity to prove his sobriety by providing an extra blood sample if desired. 
5.3. 
Remaining risks associated with the test product  
 
For the risk management process, Kontigo Care has complied with the harmonized standard ISO 
14971: 2012 Medical devices - Application of a risk management system for medical devices. 
Appropriate measures have been taken for all foreseeable safety risks that could have been linked 
to the use of TripleA as intended, or that could arise in the event of a malfunction of any of the 
components in the system. 
5.4. 
Risks associated with participation in the study 
A safety aspect that should be taken into account for the relevant patient group is that an abrupt 
release of alcohol in people who have had a long-term and high consumption of alcohol is 
associated with a risk of severe withdrawal symptoms, which can be life-threatening. However, this 
is not linked to the use of TripleA per se, but a consequence of the release of alcohol. 
5.5. 
Interactions 
TripleA does not affect concomitant pharmacological treatment. 
5.6. 
Risk reduction measures 
Usual clinical procedures must be applied to manage the risks of discontinuation of alcohol and can 
e.g. is about gradual reduction of alcohol intake or hospitalization for detoxification. 
5.7. 
Risk-benefit motivation 
 
The benefit of TripleA is judged to outweigh the risks of the current patient population, especially 
given that the method in the current study does not replace any other treatment but is used as a 
supplement to, and reinforcement of, patients' regular care. 
The risks mentioned in sections 6.3 and 6.4 above must also be set in relation to the consequences 
of continued alcohol consumption, both with regard to the patient's own health and for the co-
dependents, consequences that may be considered significantly more serious. 
 

 
 
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TripleA-enhanced aftercare after basic treatment of alcohol dependence in outpatient care 
6. The study´s objectives and hypotheses 
6.1. 
Objectives 
6.1.1. Primary objective 
The primary objective of the study is to investigate differences in alcohol consumption patterns 
between alcohol dependents who receive only conventional treatment and alcohol dependents 
who receive conventional treatment enhanced with TripleA. 
 
6.1.2. Secondary objectives 
 
 
Examine whether more patients can achieve and maintain sobriety if conventional treatment is 
enhanced with TripleA 
 
Investigate whether TripleA can contribute to fewer patients relapsing and whether relapse can 
be delayed 
 
Investigate whether TripleA can help fewer patients discontinue treatment 
 
Collect data on health outcomes as a basis for health economic analyzes 
 
To use interviews to evaluate how users experience the product TripleA in different respects 
6.2. 
Hypotheses 
By strengthening TripleA with the conventional hospital care of alcohol addicts (medicines and 
therapy calls), a larger proportion of patients is obtained who significantly reduce their alcohol 
consumption or become completely sober, thereby reducing their risk of somatic and / or mental 
injuries. 
6.3. 
Claims and performance to be verified 
The desired effect of treatment for alcohol dependence is to improve physical and psychosocial 
parameters. As a surrogate variable, however, it is accepted that you measure changes in the 
drinking pattern, which can be either absolute sobriety, or a reduction in the number of heavy 
drinking days. Regardless of how one chooses to evaluate treatments for alcohol dependence, a 
basic attitude is that if the treatment does not change the drinking pattern in a positive direction, it 
has not been successful. In this verification study, the hypothesis is that the use of TripleA enhances 
conventional treatment so that the drinking pattern with TripleA means a clinically relevant reduction 
in alcohol intake, compared with the drinking pattern without TripleA. Clinically relevant is that heavy 
drinking days do not occur. 
6.4. 
Risks and adverse effects 
 
Experiences with regard to invasion of privacy, etc. will be mapped via questionnaires to the 
participating patients / focus group interviews. 
Risks and expected undesirable effects of the test product are assessed in advance as small, but 
safety reporting during the course of the study is essential in order to be able to capture any 
unexpected effects and risks with TripleA. See also section 18 (Safety reporting). 
 
 

 
 
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TripleA-enhanced aftercare after basic treatment of alcohol dependence in outpatient care 
7. Study design 
7.1. 
Generally 
7.1.1. Type of clinical study 
 
The study is a 12-month open and randomized comparison between the control group receiving 
conventional therapy only and the intervention group receiving conventional therapy enhanced 
with TripleA. 
The study is open because it is the overall concept TripleA that is to be evaluated, which means 
that both the patient and the therapist must use the tool. A single-blind design could have been 
used if the goal had been to study the system's components, e.g. only changed patient behavior 
due to increased support or how therapists' efforts change with or without the information that 
TripleA can provide. If you want to study the combination effect, the study cannot be blinded. 
Many treatments work to achieve sobriety or controlled drinking in the short term, but it is more 
difficult to maintain the effect over time, as the problems behind drinking do not necessarily 
disappear because you stop drinking or reduce your drinking. The EMA and the FDA, 
respectively, recommend 12 or 6-month studies, as the drinking pattern at these times has been 
shown to be predictive of long-term outcomes. 
In the current studies, patients will be followed for 12 months to cover all the holidays of the year 
and other regularly recurring challenges for those who try to refrain from drinking alcohol. An interim 
analysis is performed after 6 months to obtain data that can support the system patent for TripleA. 
7.1.2. Baseline 
 
The process leading up to a treatment intervention can look very different for different patients. 
Some will therefore have been sober or significantly reduced alcohol consumption for a long time 
before it becomes relevant with visit 1. To then always use the 4 weeks preceding visit 1 as a 
baseline for Time Line Follow Back will be very wrong. It is therefore up to the care provider to, in 
consultation with the patient, define which four-week period is to be counted as the baseline in 
each individual case. It should be a continuous period of four weeks, and the most recent four-
week period that has a representative alcohol intake pattern for the period before the decision to 
seek help / initiate treatment was made. 
 
7.1.3. Measures taken to minimize or avoid bias/impact 
7.1.3.1.  Randomization 
Randomization of study participants is important to avoid the caregiver consciously or 
unconsciously distributing TripleA treatment to a certain category of patients. The patient 
population is heterogeneous, but demographic and social differences between the study arms 
should be due to chance and not other factors. The randomization takes place according to the 
principle of permuted blocks in order to distribute the patients as far as possible so that the 
individual therapists do not treat only one study arm. Each caregiver will have access to their own 
randomization list. See also section 8.8.2.  
 
7.1.3.2.  Sampling as a complement to TLFB 
The TimeLine Follow Back method relies on patients remembering and wanting to talk about their 
alcohol consumption. To improve reliability, TLFB will be combined with sampling of biomarkers for 
blood alcohol. 

 
 
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TripleA-enhanced aftercare after basic treatment of alcohol dependence in outpatient care 
7.2. 
Efficacy endpoints 
7.2.1. Primary efficacy endpoint 
 
Proportion of patients who do not have heavy drinking days 
Clinically relevant for treatment focused on risk reduction is that patients do not have heavy 
drinking days. The measurement tool will be TLFB (see Appendix C) where the number of days 
with large consumption over a four-week period is calculated. 
Heavy drinking days are the same as days with heavy consumption, which means consumption of 
4 or more standard glasses of alcohol per day for women and 5 or more standard glasses of 
alcohol per day for men. 
How to determine the TLFB at baseline is stated in section 8.1.2. Follow-up TLFB is then made at 
each visit. The primary measure of effectiveness is the difference between the treatment arms in 
the proportion of patients who do not have heavy drinking days during the 4-week period 
preceding the 12-month visit. 
 
7.2.2. Secondary efficacy endpoints 
 
Difference between the treatment arms in the proportion of completely sober patients during a 4-
week period at 6 and 12 months, respectively. 
The proportion of completely sober patients is measured with TLFB. To be considered sober, the 
patient must have entered 0 standard glasses consumed during the 4-week period preceding the 
6- and 12-month visits, respectively. 
The difference in the total amount of alcohol consumed per 4-week period after 6 and 12 months, 
respectively, compared with baseline 
The total amount of alcohol consumed per 4-week period is measured in standard glasses using 
TLFB, and is the sum of the number of glasses for the entire period. How to determine the TLFB 
at baseline is stated in section 8.1.2. Follow-up TLFB is then made at each visit.The difference in 
the number of heavy drinking days per 4-week period at 6 and 12 months, respectively, compared 
with baseline 
The number of heavy drinking days is measured with TLFB. Heavy drinking days are the same as 
days with heavy consumption, which means consumption of 4 or more standard glasses of alcohol 
per day for women and 5 or more standard glasses of alcohol per day for men. How to determine 
the TLFB at baseline is stated in section 8.1.2. Follow-up TLFB is then made at each visit. 
The difference in the number of drink-free days per 4-week period at 6 and 12 months, respectively, 
compared with baseline. 
The measuring tool becomes TLFB where the number of days of consumption specified as zero 
standard glass during a four-week period can be calculated. How to determine the TLFB at baseline 
is stated in section 8.1.2. Follow-up TLFB is then made at each visit.. 
The measuring tool becomes TLFB where the number of days of consumption specified as zero 
standard glass during a four-week period can be calculated. How to determine the TLFB at baseline 
is stated in section 8.1.2. Follow-up TLFB is then made at each visit. 
The measuring tool becomes TLFB, where the sum of the number of standard glasses for the entire 
4-week period is divided by the number of days when alcohol is consumed. How TLFB is to be 
determined at baseline is stated in section 8.1.2. Follow-up TLFB is then made at each visit. 
Time to relapse 

 
 
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TripleA-enhanced aftercare after basic treatment of alcohol dependence in outpatient care 
Depending on the goal of treatment, a relapse can be either a day of heavy consumption or drinking 
at least one standard glass of alcohol. Both recurrence measures will be evaluated. 
• The number of days before the first alcohol intake (at least one standard glass) according to the 
patient's own information. 
• The number of days before the first heavy drinking day according to the patient's own information. 
Clinical Global Impression improvements after 6 and 12 months, respectively 
The patients who after 12 months are “significantly improved” or “greatly improved”, ie they receive 
a value of 1 or 2 on the CGI-I scale (see section 8.3.6) are considered to have responded to the 
treatment (responders). Patients with a value of 3 or higher are classified as non-responders. The 
proportion of responders will be compared between the treatment arms. 
Change in quality of life measured with EQ-5D  
EQ-5D is an accepted and widely used measure of quality of life, and the form is recommended by 
TLV (Dental and Pharmaceutical Benefits Agency). A general quality of life measure such as EQ-
5D provides an overall picture of the study participants' perceived health, and is a good basis for 
health economic analyzes. 
 
AUDIT improvement 
The National Board of Health and Welfare prioritises AUDIT as a tool for identifying alcohol 
problems. The treatment arms will be compared with respect to: 
• Proportion of patients who after 12 months have lowered their AUDIT score 
• Proportion of patients who after 12 months have lowered their AUDIT score to at least one zone 
• Proportion of patients who after 12 months have a risk level <II 
(i.e. less than 6 AUDIT points for women, 8 AUDIT points for men). 
 
SADD improvement 
Change in alcohol dependence measured as the difference in SADD scores at 12 and 6 months, 
respectively, compared with baseline). 
Compliance with agreed treatment 
 
The patient remains in treatment 
At each study-related visit, it is documented whether the patient remains in treatment or has 
interrupted his or her treatment. The proportion of patients who remain in treatment will be compared 
between the patient groups over time. 
Compliance with TripleA 
For the TripleA arm, the proportion of measurements performed compared to announced 
measurements will be reported. The information is retrieved from the TripleA database where all 
notifications and measurements are logged. Corresponding information is not available for the 
control arm for obvious reasons. 
If the patient has a valid explanation for the lack of an individual blow, the caregiver can state this 
in the system, and indicate whether or not there should have been alcohol in the exhaled air at the 
time in question. 

 
 
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TripleA-enhanced aftercare after basic treatment of alcohol dependence in outpatient care 
Compliance with the agreed plan for visits to the care provider and / or visits to AA meetings 
In cases where the caregiver and patient have agreed that the patient should participate in certain 
activities, such as e.g. relapse prevention course or MI call, compliance with this plan will be 
evaluated. The ratio between the number of occasions the patient participated relative to the 
planned number is calculated and expressed as a percentage. The calculation is made per type of 
activity, eg: 
• The number of treatment meetings that the patient has participated in the last 4 weeks divided by 
the number of planned treatment meetings for the corresponding period. 
• The number of AA meetings visited in the last 4 weeks divided by the agreed number of AA 
meetings the patient would have attended for the corresponding period. 
For the TripleA arm, this information can be retrieved from the TripleA database if that function has 
been used. However, the comparison between the treatment arms is based on the information noted 
in the CRF during the visits when the patient is asked about his or her participation. For the TripleA 
arm, an analysis is then made of how large the correspondence is between the registrations in 
TripleA and the data in CRF. 
Compliance with drug treatment 
Adherence to drug treatment will not be evaluated in the context of the study. 
Change in the presence of the alcohol metabolites PEth and CDT in the blood at 6 and 12 months, 
respectively, compared with baseline. 
Phosphatidylethanol (PEth) is analyzed at Karolinska Laboratory. The concentration of PEth-16: 
0/18: 1 is given in the unit µmol / L. The PEth level in the blood reflects the alcohol consumption of 
recent weeks. PEth-16: 0/18: 1 values lower than 0.05 µmol / L indicate no or low sporadic alcohol 
consumption. Values between 0.05-0.30 µmol / L speak for regular moderate consumption, but 
even occasional very large intakes of alcohol can probably give measured values in this range. 
Low carbohydrate transferrin (CDT) shows alcohol-induced change in the glycosylation pattern of 
transferrin, which is measured in serum samples. CDT is used as a marker to demonstrate regular 
alcohol consumption and «risk use / abuse«, where the measured value reflects the intake during 
the last weeks - the month. Single major alcohol intakes do not affect CDT levels. 
Analyzed at the Academic Laboratory and reported in%. Reference interval <2.0%. 
 
7.3. 
Methods and times for measuring, registering and analyzing 
variables 
7.3.1. Short Alcohol Dependence Data (SADD) 
SADD consists of 15 questions that measure the degree of alcohol dependence using a points 
scale. The form can be answered by the therapist interviewing the patient or filling in by the 
patient himself. Estimated time consumption max 5 minutes. See Appendix B 
Time: Made at visit 1 to collect baseline data, and at 6 and 12 months. 
7.3.2. Alcohol calender– Time-Line Follow-Back 
Time-Line Follow-Back (TLFB) is a method that can be used to obtain information about patients' 
alcohol consumption. (Sobell, Maisto et al 1979). In short, it means that as far back as 3 months 
ago, you retrospectively reconstruct how many standard glasses you have consumed per day. It is 
accepted that the reporting is not an exact representation of the alcohol intake, but also that it 

 
 
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TripleA-enhanced aftercare after basic treatment of alcohol dependence in outpatient care 
provides a decent benchmark, which is also sensitive to changes in the drinking pattern. An 
alcohol calendar (see Appendix C) is used for this purpose. For study purposes, alcohol 
consumption reported via TLFB is used for the 4 weeks preceding each visit. How to determine 
the TLFB at baseline is stated in section 8.1.2. 
When filling in TLFB, the patient and therapist must consult and results of blood tests and for the 
intervention arm, TripleA measurements must also be taken into account to identify if and when 
alcohol intake has occurred. 
Information about missed measurements or measurements that show alcohol in the exhaled air 
(both for TripleA and for regular measurements at the care provider) should be used in the TLFB 
call and should in the alcohol calendar correspond to a number greater than 0 standard glasses 
on the current day. There may be discrepancies between what the patient is willing to state in the 
TLFB and the information that the caregiver has available in the TripleA caregiver portal or from 
other sources. The caregiver should talk to the patient about this, and give the patient the 
opportunity to update the information in the TLFB if necessary, but should not force the patient to 
enter a number greater than 0 or change information provided by the patient without the patient's 
consent. 
In CRF, it is possible for the care provider to state whether there are signs of alcohol intake that 
do not correspond to reported intake in TLFB. 
Time: At each visit. 
 
 
 AUDIT (The Alcohol Use Disorders Identification Test)  
AUDIT (See Appendix D) is a well-validated instrument that is useful for identifying both alcohol 
problems and high alcohol consumption. However, AUDIT is not a diagnostic tool. You get a 
picture of consumption and the degree of difficulty of the problem. AUDIT consists of ten short 
questions and check boxes for the answers. It takes 2-3 minutes to answer the form that deals 
with last year's alcohol consumption. The first three questions are about how often and how much 
you drink, the rest about the consequences of drinking. 
Time: Made at visit 1 (refers to the year before baseline), 5 and 6. 
Risknivå  
AUDIT-poäng  
Tolkning  
Zon I  
Man 0-7 
Woman 0-5 
Low risk alcohol habits 
Zon II 
Man 8-15 
Woman 6-13 
Risky alcohol habits with not necessarily an addiction 
Zon III 
Man 16-19 
Woman14-17 
Problematic alcohol habits likely 
there is an alcohol-related diagnosis 
Zon IV 
Man 20+ 
Woman 18+ 
Very problematic alcohol habits probably exist one 
alcohol-related diagnosis 
 
 
 
 

 
 
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TripleA-enhanced aftercare after basic treatment of alcohol dependence in outpatient care 
7.3.3. DUDIT (The Drug Use Disorders Identification Test)  
DUDIT (Appendix E) has been developed as a parallel instrument to AUDIT, with the aim of 
assessing whether problems with drugs (including addictive drugs) occur. Based on aggregated 
points and the distribution of these, the instruments provide information on consumption levels, 
signs of addiction development and injuries related to consumption. 
Time: Made at visit 1 
7.3.4. Questions about motivation and belief in one´s own ability 
The intention is to measure how motivated the patient is to change their drinking and whether it is 
the patient's own initiative or pressure from other parties that is behind it. The patient may also 
value confidence in their own ability to succeed with the change. The patient's own confidence in 
their ability has been shown to be predictive of treatment outcome, and a simple instrument with 
only one question has better predictive ability than more complex instruments (Ludwig et al, 
2013). The questionnaire can be found in Appendix F. 
Time: Made at visit 1 
 
7.3.5. CGI (Clinical Global Impression) Severity and Improvement Scales 
CGI is an abbreviation for Clinical Global Impression, which has been translated as "overall clinical 
impression". 
CGI-Severity (CGI-S) means that the caregiver makes an assessment of the severity of the disease 
based on the question: "In the light of your clinical experience of this particular patient population, 
how seriously mentally ill is the patient currently?" 
An answer option can be specified: 
○ Not assessed  
○ Normal, not sick at all  
○ Limit cases for mental illness  
○ Mildly ill  
○ Moderately ill 
○ Significantly ill 
○ Seriously ill  
○ Among the most extremely ill patients 
Time: Done at visit 1 
The initial CGI-S assessment then forms the basis for assessing whether the patient has improved 
or deteriorated, as indicated on the Clinical Global Impression - Improvement Scale (CGI-I) which 
is a scale from 1-7 where 1 corresponds to "significantly improved" , 2 "much improved", 3 "slightly 
better", 4 "unchanged", 5 "slightly worse", 6 "much worse", and 7 "significantly worse". 
CGI-I is done at visits 5 and 6. 
7.3.6. EQ-5D 
The EQ-5D is a standardized instrument for measuring and describing health outcomes. The EQ-
5D contains a descriptive questionnaire and a vertical visual analog scale (EQ VAS). 
The descriptive questionnaire in EQ-5D consists of questions where the individual can classify their 
own health in five different dimensions: mobility, hygiene, main activities, pain / discomfort and fear 

 
 
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TripleA-enhanced aftercare after basic treatment of alcohol dependence in outpatient care 
/ depression on a three-point scale (no, moderate and severe discomfort). The individual's answers 
to these questions form a health profile that represents a specific health condition. 
There are a total of 243 possible combinations of health conditions. On the thermometer-like scale 
(EQ VAS), the individual can describe how good or bad he feels by putting a cross on the scale 
from 0 to 100. Where 0 is the worst possible health and 100 is the best possible health. In this way, 
EQ VAS generates an individual self-rated state of health, so-called VAS score. 
Time: Made at visits 1, 5 and 6. 
7.3.7. Biological samples (blood and urine) 
Samples are ordered via the medical record system, taken and handled according to regular clinical 
routine. Patients are instructed to leave the samples some week before the visits, so that test results 
are available for the visit. 
For sampling instructions, refer to the latest updated versions on the Academic Laboratory's 
website. 
Urine samples for drug screening usually include amphetamine, benzodiazepines, burprenorphine, 
cannabis, cocaine, methadone metabolites, opiates. Verification analysis in the event of a positive 
result on a urine dipstick is performed if clinically relevant 
Time: Done at visit 1 
 
Phosphatidylethanol (PEth) is analyzed at Karolinska Laboratory. The concentration of PEth-16: 
0/18: 1 is given in the unit µmol / L. The PEth level in the blood reflects the alcohol consumption of 
recent weeks. PEth-16: 0/18: 1 values lower than 0.05 µmol / L indicate no or low sporadic alcohol 
consumption. Values between 0.05-0.30 µmol / L speak for regular moderate consumption, but 
even occasional very large intakes of alcohol can probably give measured values in this range. 
Time: Made at each visit 
Low carbohydrate transferrin (CDT) shows alcohol-induced change in the glycosylation pattern of 
transferrin, which is measured in serum samples. CDT is used as a marker to demonstrate regular 
alcohol consumption and «risk use / abuse«, where the measured value reflects the intake during 
the last weeks - the month. Single major alcohol intakes do not affect CDT levels. 
Analyzed at the Academic Laboratory and reported in%. Reference interval <2.0%. 
Time: Made at each visit 
7.3.8. The assessment phase 
 
The assessment phase must be documented in CRF with the date of the assessment interview and 
whether the patient chooses to continue with any type of treatment. If the patient refuses treatment 
efforts, the patient's participation in the study must be terminated. 
Time: At visit 1 and while the assessment phase is ongoing. 
7.3.9. Conventional treatment 
The treatment interventions that have begun, are ongoing or have ended must be documented in 
CRF. Start date, end date and scope must be stated for psychosocial interventions. For medicinal 
products, the substance, dosage form, route of administration, strength and dose frequency and 
start and end dates are indicated. Time: Made at each visit.  

 
 
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7.3.10. Treatment goal 
The goal of the treatment ("To become alcohol-free" or "To reduce alcohol consumption") is 
documented at visit 1 and any changes in goals are followed up at each visit. If the goal is to reduce 
alcohol consumption, a target level is documented. At each visit, the caregiver also makes an 
assessment of whether the patient has achieved his or her own treatment goal or not. 
7.3.11. Compliance with treatment and meeting participation 
In cases where the caregiver and patient have agreed that the patient should participate in certain 
activities, such as relapse prevention courses or AA meetings, compliance with this plan will be 
evaluated. The ratio between the number of occasions the patient participated relative to the 
planned number is calculated and expressed as a percentage. The calculation is made per type of 
activity, eg: • The number of treatment meetings that the patient has participated in the last four 
weeks divided by the number of planned treatment meetings for the corresponding period. • The 
number of AA meetings visited in the last four weeks divided by the agreed number of AA 
meetings the patient would have attended for the corresponding period. Time: Done at visits 2, 3, 
4, 5 and 6.  
 
7.3.12. TripleA 
Random measurements of alcohol in exhaled air, with identity control via mobile camera. Made on 
request via notification in mobile app - only in the TripleA arm. Reporting of results to the therapist 
takes place via the caregiver portal. 
Timing: Sleep breaks can be added by a therapist. Thereafter, the alcohol tests take place according 
to schedule daily just before and after the sleep break. A third alcohol test will take place during the 
waking time between the 2 previous tests. If desired, this can be planned to happen randomly. 
The care provider checks the care portal before each patient visit, but does not have continuous 
supervision of the system within the framework of the study, which is technically but not 
organizationally possible. 
In order for TripleA to always be usable, the mobile phone has been provided with a subscription 
that allows free calls and SMS, as well as data traffic up to 1GB per month. Kontigo Care is 
responsible for the subscription fee. The patient can use the phone during the study at no extra 
cost. 
 
7.3.13. Safety reporting 
Patients in the TripleA arm should be asked at each visit if there have been any incidents related to 
the use of TripleA. 
Alcohol-related hospitalization since the previous visit must be noted in CRF for all study 
participants. 
Time: Made at each visit. 
 
 

 
 
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7.3.14. Study overview 
Visit 
Visit 1 
Visit 2 
Visit 3 
Visit 4 
Visit 5 
Visit 6 
Protocol 
section 
Time point 
Month 
0 
Month 
1 
Month 
2 
Month 
3 
Month 
6 
Month 
12 
 
Informed consent 
X 
 
 
 
 
 
17, Error! 
Reference 
source 
not 
found. 
Inclusion and 
exclusion criteria 
X 
 
 
 
 
 
Error! 
Reference 
source 
not 
found., 
Error! 
Reference 
source 
not 
found. 
Anamnesis and 
medical examination 
X 
 
 
 
 
 
7.8.2 
Demographic data 
X 
 
 
 
 
 
7.8.2 
Beverage history 
X 
 
 
 
 
 
7.8.2 
SADD 
X* 
 
 
 
X 
X 
7.3.1 
TLFB 
X* 
X 
X 
X 
X 
X 
7.3.2 
AUDIT 
X* 
 
 
 
X 
X 
8.3.3 
DUDIT 
X 
 
 
 
 
 
7.3.3 
Motivation questions 
X 
 
 
 
 
 
Error! 
Reference 
source 
not 
found. 
CGI (S and I, 
respectively) 
XS 
 
 
 
XI 
XI 
7.3.5 
EQ-5D 
X 
 
 
 
X 
X 
7.3.6 
Urine sample  
X 
 
 
 
 
 
7.3.7 
Blood samples 
X 
X 
X 
X 
X 
X 
7.3.7 
Documentation of 
assessment and 
conventional 
X 
X 
X 
X 
X 
X 
Error! 
Reference 
source 
not 
found., 

 
 
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treatment including 
drugs 
Error! 
Reference 
source 
not 
found. 
Compliance to 
treatment 
 
X¤ 
X¤ 
X¤ 
X¤ 
X¤ 
Error! 
Reference 
source 
not 
found. 
Safety reporting 
X 
X 
X 
X 
X 
X 
7.3.13, 
Error! 
Reference 
source 
not 
found. 
Randomization 
X 
 
 
 
 
 
7.8.2 
TripleA dividend and 
registration in 
caregiver portal# 
X 
 
 
 
X 
 
7.8.2 
TripleA return# 
 
 
 
 
X 
X 
7.8.8 
*) Refers to baseline 
S) CGI-Severity 
I) CGI-Improvement Scale 
¤) Participation in agreed therapy meetings, AA meetings etc  
#) Only intervention arm. TripleA needs to be calibrated after 6 months use and will therefore be 
replaced at visit 5. 
 

 
 
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7.4. 
Equipment to be used in the clinical study to meaasure variables 
In addition to the study product, laboratory equipment is used in an accredited laboratory for routine 
analyzes of alcohol metabolites. 
7.5. 
Loss 
7.5.1. Loss of patients 
 
The reason why a patient discontinues treatment or study must be documented and these patients 
must be followed up. Patients who discontinue the study will not be reimbursed. The loss will be 
reported. 
7.5.2. Loss of individual values 
 
Missed blows are discussed with the patient during the visits. If the patient has a plausible 
explanation for the lack of a single puff, the caregiver can state this in the system, and indicate 
whether or not there should have been alcohol in the exhaled air at the time in question. A patient 
who so wishes may submit an extra blood sample to prove that he has been sober during the period 
when measurement values are missing. 
 
7.6. 
Test product(s) and comparator(s) 
7.6.1. Description of the exposure of the test product (s) or comparative product, if 
used. 
  
The test product TripleA is used by the patients in the intervention group throughout the study 
period, a total of 12 months. The patient is instructed to always carry the breathalyzer and the 
associated mobile phone. SMS notification indicates that it is time to make a measurement. The 
patient then needs to complete the measurement within 60 minutes. 
Measurement can not be done on the patient's own initiative, but only after activation via SMS 
notification. SMS notifications occur randomly several times a day, which means that the patient 
does not know in advance when it is time for the next measurement. The caregiver can set a break 
for night rest when notifications are not sent. 
 
7.6.2. Justification for the choice of comparative product 
Not applicable no comparator will be studied. 
 
7.6.3. List of other medical devices or drugs to be used during the clinical study 
 
No other medical devices or drugs will be linked to the study. However, study participants will be 
allowed to continue or start using other products and medicines in parallel with the study, provided 
that this is documented in the patient's medical record. 
 

 
 
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7.6.4. The number of product units used, and justification for this 
 
One TripleA unit per study participant is used at a time. At 6 months, the unit will need to be 
calibrated and the study participant will then be assigned a new TripleA to not be without when the 
first one is sent back to Kontigo Care for calibration. 
A total of approximately 200 units are estimated to be used within the framework of the study. 
 
7.7. 
Subjects 
7.7.1. Inclusion criteria for selection of subjects 
• Patients for whom there is a care commitment for the alcohol program at the Addiction and 
Neuropsychiatry, Akademiska sjukhuset 
• 18 years or older 
• Meets at least 2 of the criteria for addiction / substance syndrome according to DSM-5 
• Ability to understand and communicate in Swedish 
• Ability to handle the technical equipment used in the study (breathalyzer + smartphone) 
• Has a fixed point (accommodation, night rest place to charge the phone) 
7.7.2. Exclusion criteria for selection of subjects 
• Schizophrenia 
• Substance syndrome related to substances other than alcohol and nicotine 
• Impaired lung function (not able to achieve adequate exhalation volume for breathalyzer 
function) 
• The patient is cared for within the framework of LVM 
• Unsuitable to participate in the study according to the examiner's assessment 
• Has not consumed any alcohol during the 4 weeks that baseline Time Line Follow Back refers 
to. 
• Normalized CDT and PEth values in blood samples taken at visit 1. 
7.7.3. Criteria and procedures for removing subjects from the study or suspending their 
participation 
 
  Substance syndrome related to substances other than alcohol and nicotine: Screening with urine 
sample and DUDIT is done at inclusion. The test result does not have to be available before the 
subject is included in the study, but should a positive screening test be reported, the subject 
should be removed from the study. No further samples are taken within the framework of the 
study.  
   
Should the patient lose or otherwise lose the test product, it can be replaced (a limited number 
of times) and the patient does not need to be removed from the study if alcohol consumption is 
reported during the days when the measurements could not be performed and blood tests are 
performed to determine a new level of PEth / CDT . Phones that have fallen into the wrong 
hands or are misused in other ways can be deactivated by Kontigo Care. Contact Kontigo Care 
should this occur.  
 
 

 
 
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7.7.4. Time for inclusion in the study 
A subject is considered to be included in the study when the consent form is signed by both the 
subject and the study staff. 
7.7.5. Expected total time required for the clinical study 
The study is expected to start in August 2015 and end in November 2016, ie a total of 16 months. 
Recruitment of study participants is estimated to last for 4 months and each study participant is 
followed for 12 months. 
7.7.6. Expected total time required for the individual subject´s participation 
The first visit is estimated to take about 1 hour. The following visit takes about half an hour. 
7.7.7. Number of subjects to be included in the study 
 
A total of 106 patients are expected to be included in the study, divided 1: 1 between control arm 
and TripleA arm. 
 
7.7.8. Estimated time required to include this number of subjects 
The recruitment period is estimated to last 4 months. 
7.8. 
Procedures 
 
7.8.1. Case Report Form (CRF) 
In connection with each visit, the study staff must fill in the relevant section of the CRF and update 
the ongoing logs that follow the patient during the study. 
 
7.8.2. Visit 1 
• Obtaining informed consent (see also section 17) 
• Control of inclusion and exclusion criteria (see sections 8.7.1 and 8.7.2) 
• Baseline data that reflects the initial position before the patient begins the current care contact, i.e. 
before enrolling in the alcohol program. At visit 1, the study participants need to answer the 
following form with the period before enrollment in mind. 
o SADD see section 8.3.1 above and Appendix B 
o TLFB see sections 8.1.2 and 8.3.2 above and Appendix C 
o AUDIT see section 8.3.3 above and Appendix D 
If this data is available from a time representative of Baseline, and has been obtained as part of a 
regular routine before the patient signs the informed consent to participate in the current study, the 
forms do not need to be filled in again. 
• General history and medical examination (medical, neurological and psychiatric) and 
consequences of alcohol dependence on the patient's cognitive, psychological and physiological 
functions. In particular, lung function should be considered, given the ability to use TripleA. 
• Demographic data are noted in the CRF 

 
 
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o age 
o sex 
o weight 
o socio-economic factors 
• Beverage history is noted in CRF 
o Age when drinking began 
o Number of years of heavy drinking 
o Age when addiction began 
o Episodic or chronic drinking 
o previous attempts to remain sober, how long the period of sobriety was and what treatment was 
used 
• DUDIT (Drug Use Disorders Identification Test) See section 8.3.4 and Appendix E 
• CGI Severity (Clinical Global Impression Severity Score) is noted in CRF, see section 8.3.6 
• EQ-5D: See Section 8.3.7 and Appendix G 
• Documentation of the goal that the patient and the care provider have agreed on (controlled 
drinking or total sobriety) See Appendix F Motivation questions. 
• Blood samples are taken (see section 8.3.8) 
• Urine test for drug screening (see section 8.7.3) 
• Assessment phase and / or Conventional treatment is documented in CRF 
• Randomization to one of the treatment arms takes place by the care provider identifying the next 
available patient number on its list. The patient numbers must be distributed consecutively and for 
each patient number there is a code envelope that the care provider opens to find out whether the 
patient should participate in the control arm or use TripleA. 
If the patient is randomized to TripleA: 
• Distribution of TripleA 
• Registration of the patient in the care provider portal. 
• The patient is instructed on how to use TripleA and may practice using the equipment under the 
supervision of the study staff before taking the equipment home. 
• If any incidents with TripleA occur during the visit, these must be reported 
(see section 18 Safety reporting) 
Note that the assigned device number must be registered both in the care 
provider portal and on a separate list of study equipment.  
The source text is required if you want further information about the translation 
Send feedback 
Side panels 
 
 
7.8.3. Before all the following visits:  

 
 
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7.8.3.1. Checking patient status in the caregiver portal (TripleA arm only).  
 
Prior to each study visit, the study staff checks the patient's status in the care provider portal with 
regard to 
- If completed blows were performed by the right person (ID check via photo). 
- If completed blows indicate alcohol intake or not. 
- Participation in agreed meetings (if applicable). 
 
7.8.3.2.  Measures in the event of noted deviations in the care provider portal 
 
 
Deviations in the form of a positive or missed sobriety test must be discussed with the patient at 
the visit and allowed to influence the TLFB responses. 
The caregiver has the opportunity to enter status comments for an individual test, which means 
that the database will contain supplementary information - without overwriting the basic status. 
The following options are available: 
If the basic status is "Missed", the following status comments can be selected: 
• 
No alcohol 
•                      Alcohol could not be excluded 
• 
Technical issue. 
 
If the default status is "Alcohol could not be excluded", the following status comments can be 
selected: 
• 
No alcohol 
• 
Technical issue. 
 
If the basic status is "Technical error", the following status comments can be selected: 
• 
No alcohol 
•                      Alcohol could not be excluded 
 
7.8.3.3. Measures in case of detected relapses (regardless of information 
source) 
The normal process when patients have relapsed is followed, which means that for each 
individual is discussed and decided what is best in the current situation - whether it is relevant to 
change something in the treatment, work with motivation or management of triggers. If necessary, 
MI, relapse prevention and / or medication are offered.  
 
 
 

 
 
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7.8.4. Visit 2 (Follow-up after 1 month)  
 
• TLFB - See section 8.3.2 and Appendix C. 
• Blood test - See section 8.3.8. 
• Note changes in medication and other conventional treatment. Update relevant 
assessment phase information (WP2 only) - See sections 8.3.9 and 8.3.10 
• Compliance - See section 8.3.12 
• Safety reporting - See section 18 
 
7.8.5. Visit 3 (Follow-up after 2 months) 
 
• TLFB - See section 8.3.2 and Appendix C. 
• Blood test - See section 8.3.8. 
• Note changes in medication and other conventional treatment. Update assessment 
phase information if relevant - See sections 8.3.9 and 8.3.10 
• Compliance - See section 8.3.12 
• Safety reporting - See section 18 
 
7.8.6. Visit 4 (Follow-up after 3 months)  
 
• TLFB - See section 8.3.2 and Appendix C. 
• Blood test - See section 8.3.8. 
• Note changes in medication and other conventional treatment. Update the assessment  
phase information if relevant - See sections 8.3.9 and 8.3.10 
• Compliance - See section 8.3.12 
• Safety reporting - See section 18 
 

 
 
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7.8.7. Visit 5 (Follow up after 6 months)  
• TLFB - See section 8.3.2 and Appendix C. 
• Blood test - See section 8.3.8 
• AUDIT - See section 8.3.3 above and Appendix D 
• CGI Improvement Scale (Clinical Global Impression Severity Score): See section 8.3.6 
• EQ-5D: See Section 8.3.7 and Appendix G 
• SADD: See section 8.3.1 and Appendix B 
• Note changes in medication and other conventional treatment - See section 8.3.10 
• Compliance - See section 8.3.12 
• Safety reporting - See section 18 
• Check that the patient has had a new TripleA device sent home and returned the old one for 
calibration 
 
7.8.8. Visit 6  (Close-out visit after 12 months) 
• TLFB - See section 8.3.2 and Appendix C. 
• Blood test - See section 8.3.8 
• AUDIT - See section 8.3.3 above and Appendix D 
• CGI Improvement Scale (Clinical Global Impression Severity Score): See section 8.3.6 
• EQ-5D: See Section 8.3.7 and Appendix G 
• SADD: See section 8.3.1 and Appendix B 
• Note changes in medication and other conventional treatment - See section 8.3.10 
• Compliance - See section 8.3.12 
• Safety reporting - See section 18 
• Return of TripleA. 
• End the patient in the caregiver portal 
 
7.8.9. Follow up and treatment after the study 
The caregiver decides how the patient should be followed up and possibly treated after the end of 
the study. Any continued use of TripleA takes place within the framework of ordinary care. 
7.8.10. Sponsors activities 
Kontigo Care performs calibration of equipment and technical support for TripleA. 
7.8.11. Factors that can affect the result 
 
How motivated the patient is to abstain from alcohol will have an impact on whether one succeeds 
in abstaining from drinking alcohol during the course of the study. However, in order to make a 
study as realistic as possible, patients will not be selected depending on how motivated they are. 

 
 
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On the other hand, motivational factors will be mapped (see Appendix F) and thus you can get 
information on whether the degree of motivation in the two treatment groups is comparable or not, 
and whether it is possible to link the degree of motivation to the treatment result. The degree of 
severity of the dependence and the possible impact of demographic and social factors on the 
result will also be taken into account with exploratory analyzes. 
The trust between therapist and patient can be of great importance for the treatment result and 
even if the methodology applied by the therapists is the same, it is conceivable that it matters 
which therapist you meet. Therefore, the randomization procedure will ensure that each therapist 
treats patients in both treatment arms to the greatest possible extent. 
The treatment the patient receives may play a role in how the patient succeeds, but there is a lack 
of unambiguous data that suggests that a certain treatment works better than others, both in 
general and for specific patient groups. We therefore allow a wide range of treatment methods as 
background treatment in the clinical studies with TripleA. Descriptive statistics will be presented 
for what the distribution of treatment methods looks like in the various treatment arms. The patient 
material in the current study is probably too small to be able to draw any conclusions as to 
whether any treatment works better or worse in combination with TripleA, but exploratory 
subgroup analyzes will be performed. 
The efficacy measures based on self-reported TLFB data may be affected if patients provide 
incorrect information in an attempt to protect their addiction and to conceal their possible drinking. 
In this study, the probability of a recurrence being detected is lower in the control arm than in the 
TripleA arm. This risks giving an incorrect comparison as frequent measurements in the TripleA 
arm (at least 3 times a day) increase the possibility of detecting the use of alcohol, which would 
otherwise have gone unnoticed. TLFB data can also be affected and provide more honest 
reporting as the patient knows that even shorter relapses risk being detected through the frequent 
alcohol tests. This could mean that even if the actual alcohol use in the TripleA arm is lower than 
in the control arm, we get more reports of alcohol use in the TripleA arm. 
However, it is reasonable to assume that even if more alcohol intake is detected with TripleA, the 
actual alcohol intake pattern is not worse in the TripleA arm than in the control arm. It is also an 
advantage that relapses and alcohol intake become clear to both the patient and the therapist, in 
order to be able to work with relapses and the factors that trigger them within the framework of the 
treatment. The earlier you can stop a risky alcohol intake, the less the consequences for both the 
patient and the environment. 
Although more relapses would be detected in the TripleA arm due to the frequent measurements, 
there is a possibility that the support that the system provides to maintain sobriety leads to more 
patients completing the entire treatment and participating in aftercare throughout the study period. 
Our hypothesis is therefore that the proportion of patients without heavy drinking days is more and 
the proportion who carry out the entire aftercare is more in the arm where the care and aftercare 
has been strengthened with TripleA. 
When the study was designed, it was considered within the framework of the study to carry out 
more frequent checks of biomarkers to get a "real" result also for the control arm's alcohol intake, 
but the choice was made not to introduce more frequent biomarker controls (which in itself can have 
a deterrent effect on alcohol intake, to the price of further restrictions in the patient's daily life and 
increased costs for laboratory analyzes). One of the reasons for this choice is that the results of the 
study should be able to be compared with the interventions the patients currently receive. 
 
8. Monitoring plan 
The planned monitoring of the study, including verification of source data, is described in a 
separate monitoring plan. 
 

 
 
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9. Statistical considerations 
9.1. 
Statistical design, method and analysis procedure 
9.1.1. General 
 
Continuous data will be summarized using descriptive statistics where the following parameters 
will be reported: number of observations, number of missing observations, mean, standard 
deviation, median, minimum and maximum. Categorical data will be presented with number (n) 
and percentage (%). 
In addition to evaluation of all study data from the entire study period (12 months), 6-month data 
will also be evaluated. 
Factors such as gender, severity of addiction, motivation, form of therapy and socio-economic 
factors will be considered as covariates in the statistical analyzes. 
9.1.2. Efficacy evaluation 
 
9.1.2.1. Primary efficacy endpoint 
 
Proportion of patients who do not have heavy drinking days. A logistic regression model will be 
used to compare the groups. 
Clinically relevant for treatment focused on risk reduction is that patients do not have heavy 
drinking days. The measurement tool will be TLFB (see Appendix C) where the number of days 
with large consumption over a four-week period is calculated. 
Heavy drinking days are the same as days with heavy consumption, which means consumption of 
4 or more standard glasses of alcohol per day for women and 5 or more standard glasses of alcohol 
per day for men. How to determine the TLFB at baseline is stated in section 8.1.2. Follow-up TLFB 
is then made at each visit. 
9.1.2.2. Secondary efficacy endpoints 
 
i) 
Change in total amount of alcohol consumed per 4-week period after 6 
months from “baseline.” An ANOVA model for repeated measurements will 
be used to compare the groups. 
ii) 
Change in total amount of alcohol consumed per 4-week period after 12 
months from “baseline.” An ANOVA model for repeated measurements will 
be used to compare the groups. 
iii) 
Proportion of completely sober patients at 12 months A logistic regression 
model will be used to compare the groups. 
iv) 
Proportion of completely sober patients at 6 months. A logistic regression 
model will be used to compare the groups. 
v) 
Change from baseline in the number of heavy drink days per 4-week period 
at 6 and 12 months, respectively. An ANOVA model for repeated 
measurements will be used to compare the groups. 
vi) 
Change from “baseline” in the number of non-drinking days per 4-week 
period at 6 and 12 months, respectively. An ANOVA model for repeated 
measurements will be used to compare the groups.Förändring från 
”baseline” i antalet standardglas per dryckesdag per 4-veckorsperiod vid 6 
and 12 months, respectively. vii) Time to relapse (ie first alcohol intake). For 

 
 
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patients with the goal of becoming alcohol-free, relapse is defined as the first 
day after “baseline” where alcohol consumption was found, while relapse for 
patients with the goal of reducing alcohol consumption is defined as the first 
day after “baseline” where heavy alcohol consumption is found. Heavy 
consumption is defined for women as a day with 4 or more glasses, while for 
men it is defined as a day with 5 or more glasses. The data sources TripleA, 
TLFB or blood samples are used to detect recurrence. To compare the 
survival curves, ie. the variable time to recurrence, between the treatment 
groups a log-rank test will be used. 
vii) 
CGI improvement. The proportion of respondents at follow-up visits is 
compared between the groups with a logistic regression model. 
viii) 
EQ-5D. The groups are compared regarding change from “baseline” with 
ANOVA model. No significant difference is expected, as quality of life forms 
are generally not particularly sensitive to change after treatment. 
ix) 
Participation in treatment. To compare the survival curves, ie. the variable 
time until the treatment is stopped, between the treatment groups a log-rank 
test will be used. 
x) 
Compliance with TripleA. The proportion of measurements performed by 
those announced is calculated and reported for the TripleA arm. 
xi) 
Compliance with the agreed plan for visits to the care provider and / or visits 
to AA meetings. The treatment groups are compared with respect to the 
proportion of visits performed based on CRF data with a logistic regression 
model. For the TripleA arm, the corresponding data collected via TripleA and 
the correspondence between TripleA and CRF data are also evaluated. 
xii) 
Alcohol metabolites in the blood. Changes from baseline to 6 and 12 months, 
respectively, in PEth and CDT levels are calculated and the treatment 
groups are compared with an ANOVA model for repeated measurements. 
xiii) 
Evaluation of AUDIT data. The treatment arms will be compared with respect 
to: 
xiv) 
- The proportion of patients who after 12 months have lowered their AUDIT 
score 
xv) 
- The proportion of patients who after 12 months have lowered their AUDIT 
score to at least one zone 
xvi) 
 - Proportion of patients who after 12 months have a risk level <II (i.e. less 
than 6 AUDIT points for women, 8 AUDIT points for men). 
 
xvii) Evaluation of the number of "reds" and the number of missing blows in TripleA. 
TripleA generates new types of high-resolution data that need to be handled in this 
and future clinical trials. In the simple case, the patient performs all agreed alcohol 
tests. For these, we can easily calculate the frequency of negative and positive 
alcohol tests in relation to a limit value for alcohol in the exhaled air. A fully sober 
patient has then probably performed 90 (3 / day) negative alcohol tests for 30 days 
in a month and can be considered 100% sober. A positive alcohol test (> 0.1 mg / 
ml = 0.2 ‰) gives a sobriety that is 1/90 = ~ 99% or if it is calculated per day it will 
be 96.6% (29/30). What can be more complicated is to correlate this new type of 
high-resolution data with e.g. the number of days with large consumption from 

 
 
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patient-reported data in TLFB form. If there are 3 positive blows in one day, it is 
very likely also a heavy drinking day (≥4 standard glasses / day for women, ≥5 
standard glasses / day for men), which is medically serious. If there are alcohol 
tests performed in the evening 3 different days with just over 0.2 ‰, it can 
correspond to 2 glasses of wine for dinner - which can be completely acceptable if 
the goal is to reduce drinking and its somatic and psychological consequences (risk 
reduction). If you detect around 0.2 ‰ in the morning 3 different days, it can be 
serious and very well mean 3 heavy drinking days where the alcohol consumption 
took place after the last alcohol test in the evening and the body did not have time 
to burn all alcohol before the next test in the morning. 
The second thing to deal with is missed alcohol tests. These may be due to the 
patient being sober but for various reasons not being able to perform the alcohol 
test in time (not noticed the notification, flight, mobile data shadow, etc.) or relapse 
into alcohol consumption. Here, the patient can contact the care provider (or vice 
versa) and clarify what happened. 
The caregiver has the opportunity to enter a new classification for an individual test 
in the caregiver portal, which means that the database will contain supplementary 
information - without overwriting the basic status. The following options are 
available for missed tests: 
• 
No alcohol 
• Alcohol could not be excluded 
• 
Technical issue. 
If the default status is "Alcohol could not be excluded", the following status 
comments can be selected: 
• 
No alcohol 
• 
Technical issue. 
If the basic status is "Technical error", the following status comments can be 
selected: 
• 
No alcohol 
• Alcohol could not be excluded 
The patient also has an opportunity to show that they have not had a relapse by 
submitting blood samples for analysis of PEth and CDT. The caregiver can then 
reclassify the missed alcohol tests as above. 
Even if the caregiver indicates a new classification on a test performed or missed, 
the original data always remains, which is so that the percentage sobriety can be 
calculated in two ways: 
o Proportion of sober tests based on all alcohol tests performed. 
o Corrected proportion of sober tests where both performed and missed alcohol 
tests are taken into account, with the classification made by the care provider as 
above. 
 
 
 

 
 
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9.1.3. Explorative analyses 
 
We will initially summarize data from the TripleA alcohol tests as the proportion of sober days (both 
based on tests performed and corrected values (as above)) over a 4-week period immediately 
before a visit (1, 2, 3, 6.11 months). A positive alcohol test is> 0.10 mg / L alcohol in the breath test. 
The effect will be calculated against TLFB data transformed in a similar way. We will also perform 
correlation studies between TripleA and reported levels of PEth and CDT in blood samples. 
The primary and secondary efficacy measures analyzed based on TLFB data will be compared with 
corresponding analyzes that also take into account blood test data and TripleA results. 
9.2. 
Sample size, significance level and statistical strength 
The primary endpoint is the proportion of patients who do not have heavy drinking days during a 4-
week period after 12 months from baseline. Assuming that the proportion is 30% in the control group 
and you want to be able to detect a difference of 30% between the TripleA and the control group, 
42 patients are needed per treatment group to achieve a strength of 80% with a double-sided test 
of 5% significance level. Assuming that the proportion of patients who do not complete the study is 
about 20%, a total of 106 patients need to be randomized, ie 53 per group. 
Expected loss 
The drop-out rate in alcohol studies is usually quite large. 
At inclusion, the patient is asked to provide at least one contact person that the study staff can 
contact if the patient is absent from agreed meetings, interrupts treatment and / or stops blowing. 
Patients who do not wish to continue their treatment should be informed that they are welcome to 
continue using TripleA and / or alcohol, or otherwise report their alcohol consumption, as this is 
valuable information for the study. If the patient wants to stop the study completely, the study staff 
should at least ask the question "how many standard glasses have you drunk the most in one day 
since we were last seen?". This gives the opportunity to assess whether there has been a heavy 
drinking day or not. 
A certain loss of patients during the course of the study is expected. Three types of missing data 
can be identified. 
1. Patients who choose to discontinue treatment and study participation. 
2. Patients who choose to discontinue treatment but who continue to provide information on alcohol 
intake (i.e. remain in the study) 
Patients who continue treatment but who do not provide complete information on alcohol intake. 
4. Patients who miss occasional visits. 
All efficacy evaluations will be performed on two analysis populations, a population consisting of all 
randomized patients contributing efficacy data from at least one baseline visit (ITT) and a population 
consisting of all patients who completed the study according to the protocol (PP). 
In the first population, missing values will be handled primarily according to the principle of multiple 
imputation (MI). In this approach, the missing values according to type 1 in the list above will be 
directly imputed according to the MI principle while values of type 2 in the list above, i.e. which are 
collected after treatment interruption, will remain as missing values, which are then imputed. Missing 
values of type 3 in the list above, ie. incompletely completed alcohol intake data, are replaced 
according to the principles described for each variable in section 8.3, ie. in these situations there is 
data and thus MI does not need to be used. For missing values of type 4 in the list above, MI is 
used. 

 
 
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In addition to the MI approach, any exploratory analyzes will be made where the principle of last-
observation-carried-forward (LOCF) can be used, as well as an analysis where only observed 
values are included in the evaluation. 
In addition to the above, a separate evaluation will be made for patients according to type 2 in the 
list above where collected values after treatment interruption are used. When tabulating alcohol 
intake data from visit 1 to visit 6, this group will be reported on three lines where line 1 indicates the 
number of patients in this group who remain on the treatment at each visit, while line 2 indicates the 
number of patients in this group who discontinued treatment from each visit . The third row then 
constitutes the sum of row 1 and row 2, i.e. the whole group of patients in the active group who 
discontinued treatment at some point after visit 1 but still remained in the study. 
The analyzes performed on the ITT population will be considered as the primary ones. 
The safety assessment will be based on the ITT population. 
9.3. 
Interim analysis 
 
In order to support the system patent for TripleA, an interim analysis will be made of the following 
data insofar as they are available before 4 May 2016: 
• The proportion of patients who remain in treatment / aftercare in each study arm. 
• Proportion of patients who have relapsed in each study arm. 
• The app contains questions about daily mood. Modeling will be done on the relationship between 
daily mood and recurrence rate. 
The results will only be summarized in a report that must be attached to a patent application. Data 
will not be available more than for the limited group performing the analysis. The results will not be 
available to those who work practically with the study. 
10. 
Data management 
Procedures for data management are described in a separate data management plan. 
11. Changes to the study protocol 
 
Changes to the study protocol must be decided by a representative of Kontigo Care AB and 
documented in writing. An updated version of the Protocol, with a new version number and date, 
shall be distributed to all interested parties. If the patient information is affected by the change, a 
new version of the patient information must also be produced. Depending on what the change is, it 
can be decided that the new version will be distributed to already recruited study participants, and / 
or that it will be used in connection with the consent process for new study participants. 
Kontigo Care decides whether the change in the study protocol and / or the patient information is of 
a material nature and due to this needs to be approved by the ethics review board. The responsible 
researcher then needs to submit an amendment application to the Ethics Review Board and await 
approval before the amendment can be implemented. 
 
 
 

 
 
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12. Deviations from the study protocol  
 
The examiner may not deviate from the study protocol, except in emergency situations where 
deviations from the protocol may be made without the approval of the sponsor or the ethics review 
board, if this is necessary to protect human rights, safety and well-being. Such deviations must be 
documented and reported to the sponsor and the ethics review board as soon as possible. 
Deviations / changes that affect the subjects' safety, rights and well-being, or the scientific integrity 
of the study must be submitted to the Ethics Review Board before they are implemented, except 
for the emergencies mentioned above. 
Deviations from the study protocol must be reported to and documented by the project manager. 
The project manager discusses with the sponsor each deviation in order to reach an agreement on 
what measures are appropriate to take. When the study is analyzed and reported, this must include 
any deviations from the study protocol. 
13. Responsibility for the test products 
Access to the test products must be limited and the test products may only be used within the clinical 
study and in accordance with the study protocol. 
The sponsor must keep documentation of the physical location of all test products from the time 
they are sent to the test site until they are returned or destroyed. 
The principal examiner or a delegated staff member shall maintain a distribution log of the receipt, 
use, return and destruction of the test products, which shall include: 
• date of receipt, 
• identification of each test product (batch number / serial number or unique code), 
• expiry date, if applicable; 
• date of use, 
• subject ID, 
• date when the test product was returned / removed from the subject, if applicable, 
• date of return of unused, expired or malfunctioning test products, if applicable. 
14. Compliance with laws, guidelines and standards 
 
This clinical study shall be conducted in accordance with the ethical principles that originate in the 
Declaration of Helsinki (Declaration of Helsinki, 2013) in accordance with the international standard 
ISO 14155: 2011 and European and Swedish legislation. 
The clinical study shall not begin until approval / positive opinion has been obtained from the ethics 
review board. 
If the Ethics Review Board sets any additional requirements in its opinions, these will be complied 
with. 

 
 
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15. Insurance 
 
The study participants are covered by the care provider's patient injury insurance with 
Patientförsäkringen LÖF (County Council's Mutual Insurance Company). 
16. Informed consent 
 
Patients are informed before the start of the study both orally and in writing by study staff at the 
reception. It is emphasized that participation is voluntary and that the subject can withdraw his or 
her consent at any time without this affecting the patient's future care and treatment. The patient 
must have the opportunity to ask questions to the staff and have them answered before taking a 
position on the participation. If the patient chooses to participate after reading the patient 
information, the consent form is signed and dated by both the patient and the study staff. The 
patient must be sober when taking a stand 
The patient may keep a copy of the entire patient information, including the consent form. 
 
17. Safety reporting 
17.1. 
Definitions 
17.1.1. Adverser Event (AE) 
An adverse medical event, accidental illness or injury, or adverse clinical signs (including an 
abnormal laboratory finding) in subjects, users or other persons, whether or not the event is 
related to the evolving medical device. 
NOTE 1: This includes events related to the test product or comparison product. 
NOTE 2: This includes events related to the procedures involved (all procedures in the study 
protocol) 
NOTE 3: For users and other people, this is limited to events related to the test product. 
 
17.1.2. Adverse Device Effect (ADE) 
 
Adverse medical event related to the use of a medical device under development. 
NOTE 1- This includes unwanted medical events due to deficiencies or inaccuracies in the 
instructions for use, setup, implantation, installation, use or function of the medical device under 
development. 
NOTE 2- This includes events caused by user errors or unintentional misuse. 
17.1.3. Device deficiency 
 
Deficiencies in a medical device that are linked to its identity, quality, durability, reliability, safety or 
performance, such as malfunction, misuse or user error and lack of labeling. 

 
 
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17.1.4. Serious Adverse Device Effect (SADE) 
 
Adverse medical event related to the use of a medical device under development which has 
resulted in any of the following characteristics of a serious adverse medical event. 
 
17.1.5. Serious Adverser Event (SAE) 
 
Adverse medical event such as: 
a) led to death; 
(b) has led to a serious deterioration in health which either: 
1) resulted in a life-threatening illness or injury or 
2) resulted in a permanent disability or permanent bodily injury, or 
3) required hospitalization (hospitalization) or extended an already ongoing hospitalization, 
or 
4) resulted in a medical or surgical measure being taken to prevent life-threatening illness, 
damage a permanent disability or permanent bodily injury 
c) led to fetal effects, fetal death, congenital abnormalities or malformations. 
NOTE 1: This includes product defects that could have caused a serious adverse medical 
event if a) appropriate action had not been taken or b) action had not been taken or c) if 
circumstances had been less successful. These must be handled within the SAE reporting 
system. 
NOTE 2: A planned hospital stay for an existing medical condition, or a procedure required 
by the study protocol, without serious deterioration of health is not considered a serious 
adverse medical event. 
 
17.1.6. Unanticipated Serious Adverse Device Effect (USADE) 
 
Serious adverse event occurring related to the use of a medical device under 
development, which by its nature, occurrence, severity or consequence has not been 
described in the most recent version of the risk analysis report. 
NOTE: Foreseen: An effect that by its nature, occurrence, severity or consequence has 
been described in the latest version of the risk analysis report 
 

 
 
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17.2. 
Time frames for reporting 
 
When a CE-marked product is studied within the intended use, the general obligation for 
manufacturers according to LVFS 2003: 11 applies, which is clarified in the Medical Products 
Agency's guide “Manufacturers' obligation to report accidents and incidents with medical devices” 
revised 2011-11-10 
The manufacturer is obliged to report accidents and incidents, ie: 
Any malfunction or deterioration of a product's properties or performance as well as defects and 
deficiencies in the labeling or instructions for use that may lead to or have led to 
The death of a patient, a user or another person, or 
• a serious deterioration in the health of a patient, a user or another person. 
The manufacturer must report incidents to the relevant authority, in Sweden the Medical Products 
Agency IMMEDIATELY, which in turn requires rapid reporting from the responsible examiner to the 
manufacturer. 
The following time frames for reporting apply in the event of an accident or incident with a medical 
device that involves: 
Serious danger to public health: IMMEDIATELY (without delay which cannot be justified). This 
means that the notification should not be made later than 2 calendar days after the manufacturer 
has become aware of the danger. 
Death or unexpected serious deterioration of health: IMMEDIATELY (without delay which cannot 
be justified) after the manufacturer has clarified the link between the product and the accident or 
incident. This means that the report should not be made later than 10 calendar days after the 
accident or incident became known to the manufacturer. 
Other: IMMEDIATELY (without delay which cannot be justified) after the manufacturer has clarified 
the link between the product and the accident or incident. This means that notification should not 
be made later than 30 calendar days after the accident or incident became known to the 
manufacturer. 
The caregiver's obligations are found in the National Board of Health and Welfare's regulations 
SOSFS 2008: 1, see excerpt below. 
Investigation and assessment 
If a negative event or incident has occurred with a medical technician 
product, shall 
• an investigation is initiated as soon as possible and 
• an assessment is made as to whether what happened should be reported. 
Before the investigation of the incident or incident is completed, the reasons for what happened 
must be determined as far as possible. If the investigation shows that there are shortcomings in the 
quality of the business, improvement measures must be taken. The investigation, assessment and 
measures taken must be documented. 
 
 
  

 
 
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Duty to report 
 
Notification to the manufacturer and to the Medical Products Agency of a negative event or incident 
with a medical device must be made as soon as possible on the form "Report of adverse events 
and incidents with medical devices" 
The notification obligation must be fulfilled by the person who has been appointed as the person 
responsible for notification by the operations manager. 
The report must be made in the event of a malfunction and deterioration of a product's properties 
or performance, as well as in the event of errors and deficiencies in the labeling or instructions for 
use that may lead to or have led to 
The death of a patient, a user or another person, or 
• a serious deterioration in the health of a patient, a user or another person. 
Disposal of medical device 
The product identity must be ensured for each medical device that has been involved in a negative 
event or incident. 
The product or products, together with the instructions for use and packaging, must be used to 
enable a further investigation of the incident or incident. 
However, the product or products may still be used before the investigation is completed, if 
alternative medical devices are lacking in the business and the purpose is to protect people's lives 
and health. 
Additional information about and examination of medical device 
The care provider must assist the manufacturer and the Medical Products Agency with the additional 
information, in addition to notification, that may be needed to investigate a negative event or 
incident. 
The care provider must also, as soon as possible after a notification has been received and on 
conditions specified by the care provider, provide the manufacturer with an opportunity to examine 
the medical device that has been used in the care provider's premises. 
 
17.3. 
Content of the report 
 
The reporting shall state: 
• Date when the unwanted medical event began ' 
• How it was treated 
• How it went 
• The doctor's assessment of the severity of the event and the causal relationship with the test 
product. 
The information is filled in the form "Report of adverse events and incidents with medical devices" 
(Inspektionen för Vård och Omsorg) 
 

 
 
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17.4. 
Malfunction reporting 
 
Malfunctions and deviations that have occurred must be reported in accordance with the care 
unit's own routine for deviation reporting. In addition, Kontigo Care must be informed. The 
appropriate format is the IVO form "Reporting of adverse events and incidents with medical 
devices" 
At Kontigo Care AB, errors and deviations are documented in non-conformity form, which are 
reported on to the company's QA manager. The QA Manager is responsible for maintaining a non-
conformity log of all discrepancies. 
17.5. 
Expected adverse medical events 
 
As patients will be monitored for alcohol use in the study, some patients may be expected to choose 
to use other drugs instead, which may be considered undesirable from a medical point of view. 
Within the framework of the study, drug screening will not be done, but to the extent that routine 
care reveals that patients use drugs, this must be reported as an undesirable medical event. 
If the meter is tampered with, damaged or has not been calibrated within the given time frame, the 
meter may give incorrect results. If this is suspected, the patient should contact the care provider 
so that a compensation meter can be obtained. 
Oral alcohol caused e.g. of mouthwash, food, exposure to solvent vapors and the use of rubbing 
alcohol may be sufficient to give a positive result in an alcohol test in exhaled air, even though the 
patient is sober and has no alcohol in his blood. TripleA is therefore programmed so that the patient 
has the opportunity to do a new test within 15 minutes, which overwrites the first result. 
The care portal in TripleA is developed to fit a limited number of browsers, and can work poorly in 
other versions. In order to avoid disturbances, the care provider should check that the browser used 
is supported by Kontigo Care AB. 
17.6. 
Contact information for reporting 
 
To report serious adverse events and serious adverse events related to the use of TripleA, the CRF 
form must be scanned and emailed to Kontigo Care: 
email: markku.hämäläinen@kontigocare.com 
and / or sent to 
Kontigo Care AB 
Att: Markku Hämäläinen 
Box 11008 
750 11 Uppsala 
 

 
 
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17.7. 
Data Monitoring Committe 
Not applicable. 
18. Exposed/extra vulnerable population 
 
Some of the patients who may be eligible for the current study have conditions associated with the 
treatment for alcohol dependence. This may be, for example, that employment, the possibility of 
regaining a driving license or contact with minor children is affected by how one handles their 
treatment and where there are sometimes agreements or agreements that regulate the care 
provider to report deviations. The fact that the patient participates in this study could mean that the 
care provider becomes aware of information that would not otherwise have emerged, which in turn 
could have significance in situations described above. However, the fact that a possible relapse is 
noticed and that the patient receives help to deal with this is judged to have long-term positive 
effects for the patient. 
19. Interruption or premature termination of the clinical trial 
 
The study may be terminated prematurely if: 
• Kontigo Care AB gets into financial difficulties or ceases 
• It is not possible to recruit a relevant number of subjects within a reasonable time. 
• The safety profile of the product is changed so that the risk-benefit balance is no longer acceptable. 
• Kontigo Care AB has business reasons to discontinue the study. 
In the event that the subject's participation in the study is interrupted for any of the reasons above, 
the conventional underlying treatment shall continue according to plan. Only study-related studies 
and the use of TripleA will be discontinued. 
 
20. Interview study 
 
To investigate users' experience of TripleA, a qualitative interview study on user experiences will 
be conducted with participants from this and another clinical study. The advantages and 
disadvantages of the technology will be explored, with a special focus on goal fulfillment, usability 
and integrity issues. 
Issues 
• Does the patient feel that Triple A is a support for achieving stable sobriety? If so, in what way? 
What factors are decisive? 
• How does the patient experience the usefulness? Advantages and disadvantages of the 
technology from an integrity point of view? 
• What could be changed to achieve the greatest possible benefit for the patient? 
Interviews are conducted with 12-15 patients of both sexes who have used TripleA. The 
interviews, which are estimated to take a maximum of one hour, are semi-structured with an 
interview guide that includes the above-mentioned question areas. After a test interview, any 
adjustments are made to questions. Collected data is analyzed with deductive content analysis, 

 
 
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coded and combined into categories. A separate patient information for participation in the 
interview survey will be used. 
Method references: 
Patton, M. Q. (2002). Qualitative Research and Evaluation Methods. London: Sage Publications. 
Rhodes, T., & Coomber, R. (2010). Qualitative methods and theory in addictions research. In P. G. 
Miller, J. Strang & P. M. Miller (Eds.), Addiction research methods (pp. 59-78). Chichester, UK: 
Blackwell Publishing. 
 
21. Publication policy  
Kontigo Care AB has the right to delay the publication of discoveries and inventions related to the 
company's product TripleA by 6 months to patent new inventions and to strengthen already filed 
patent applications. 
 
22. References 
Behandlingsprogram Alkoholprogrammet Beroendemottagningen, verksamhetsområde beroende- 
och neuropsykiatri, Akademiska sjukhuset, senast reviderat juni 2012 
Clinical Evaluation Report Kontigo TripleA KC001-052V01 
Clinical investigation of medical devices for human subjects – Good Clinical Practice (EN ISO 
14155:2011) Europeisk och svensk standard för klinisk prövning av medicintekniska produkter – 
God klinisk praxis  
Declaration of Helsinki; 64th WMA General Assembly, Fortaleza, Brazil, October 2013 
European Commission DG Health and consumer, Medical Devices Guidance document-
Classification of medical devices, MEDDEV 2.4/1 Rev. 9, June 2010 
European Commission DG Enterprise, Medical Devices Guidance document- Medical devices with 
a measuring function, MEDDEV 2.1/5 June 1998 
European Medicines Agency; Guideline on the development of medicinal products for the treatment 
of alcohol dependence, 18 February 2010 EMA/CHMP/EWP/20097/2008  
Food and Drug Administration, Center for Drug Evaluation and Research; Alcoholism: Developing 
Drugs for Treatment, Draft Guidance for Industry, (15003dft.doc 02/09/15) Distributed for comments 
only, February 2015  
Helander A. Biomarkörer kan fånga tidigt riskbruk av alkohol, Läkartidningen nr 45 2011,volym 108 
Helander A. , Péter O. Zheng Y.  Monitoring of the Alcohol Biomarkers PEth, CDT and EtG/EtS in 
an Outpatient Treatment Setting, Alcohol and Alcoholism Vol 47, No 5, 552-557, 2012 
Johansson, P., Jarl, J., Eriksson, A et al. (2006) The Social Costs of Alcohol in Sweden 2002 
(SoRAD Rapportserie, nr 36). Stockholm: Stockholms universitet, SoRAD. 
Klinisk handbok 2014 Alkohol -Riskbruk, missbruk och beroende, Alkoholsyndrom Ett beslutsstöd 
vid utredning och behandling av Tobias Eriksson, Chefsöverläkare Beroende & Neuropsykiatri, 
Akademiska sjukhuset.  
Ludwig, F., Tadayon-Manssuri, E., Strik, W. and Moggi, F. (2013), Self-Efficacy as a Predictor of 
Outcome After Residential Treatment Programs for Alcohol Dependence: Simply Ask the Patient 
One Question! Alcoholism: Clinical and Experimental Research, 37: 663–667 

 
 
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Mini-D 5: diagnostiska kriterier enligt DSM-5 / American Psychiatric Association ; [översättning till 
svenska av Jörgen Herlofson] Stockholm: Pilgrim Press, 2014 
Provtagningsanvisningar B-Fosfatidyletanol, Karolinska universitetslaboratoriet, reviderade 2014-
12-15 
Raistrick, D., Dunbar, G., & Davidson, R., (1983). Development of a questionnaire to measure 
alcohol dependence. British Journal of the Addiction, 78, 89-95. 
Risk analysis report Kontigo Triple-A 1.0, KC001-028V02 
System Hazard Analysis Kontigo Triple-A 1.0, KC001-06V03 
van Amsterdam J and van den Brink W.,(2013) Reduced-risk drinking as a viable treatment goal in 
problematic alcohol use and alcohol dependence, Journal of Psychopharmacology 27(11) 987-997  
World Health Organization (WHO) Global status report on alcohol and health 2014 

 
 
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Appendix A  
 
Alcohol use syndrome according to DSM-5 
A problematic pattern of alcohol use leading to clinically significant impairment or suffering, 
manifested in at least two of the following over a 12-month period: 
1. Often drink alcohol in larger quantities or for a longer period than intended. 
2. There is a persistent desire or unsuccessful attempt to limit or control drinking. 
3. A lot of time is spent acquiring alcohol, drinking alcohol or recovering after drinking alcohol. 
4. Alcohol craving, or a strong desire or longing to drink alcohol. 
5. Repeated drinking which leads to the person failing to fulfill his duties at work, at school or at 
home. 
6. Continued drinking despite constant or recurring problems of a social or interpersonal nature 
caused or exacerbated by the effects of alcohol. 
7. Important social activities, occupational or leisure activities are abandoned or reduced due to 
drinking. 
8. Repeated drinking in situations where it entails significant risks of physical harm. 
9. Drinking continues despite knowledge of persistent or recurrent physical or mental disorders 
that are likely to be caused or exacerbated by alcohol. 
10. Tolerance, defined as either of the following: 
a. Need for significantly increased amount of alcohol to achieve intoxication or other desired 
effect. 
b. Significantly reduced effect with continued consumption of unchanged amount of alcohol 
11. Abstinence, as manifested in either of the following: 
a. An abstinence syndrome that is typical of alcohol (see criteria A and B for alcohol abstinence 
below). 
b. Alcohol (or a similar substance, such as a benzodiazepine preparation) is used for the purpose 
of relieving or avoiding abstinence  symptoms. 
 
 
 
 
 
 
 

 
 
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Alcohol abstinence according to DSM-5 (excerpt only criteria A and B, not complete text). 
A. The person has stopped or reduced long-term and intense alcohol use. 
B. At least two of the following have developed within a few hours to a few days after cessation 
(or reduction) of alcohol consumption according to criterion A: 
Autonomic hyperactivity (eg sweating or heart rate above 100 beats / min). 
2. Increased hand tremor. 
3. Sleep disturbance. 
4. Nausea or vomiting. 
5. Transient visual, tactile or auditory hallucinations or illusions. 
6. Psychomotor agitation. 
7. Anxiety. 
8. Generalized tonic-clonic seizures.Källa: Mini-D 5 : diagnostiska kriterier enligt DSM-5 / American Psychiatric Association ; [översättning till svenska av Jörgen 
Herlofson] Stockholm: Pilgrim Press, 2014 

 
 
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Appendix B 
Short Alcohol Dependence Data Questionnaire (SADD) 
These questions give an idea of the severity of alcohol dependence. 
The questions are about how you think and act around alcohol. Read each question carefully, but 
do not think too long before answering. Think about how you have been drinking lately. 
 
DO THIS: 
Answer each question by calling the option that applies to you. 
QUESTIONS 
NEVER 
SOMETIM
ES 
OFTEN 
ALMOST 
ALWAYS 
1. Is it hard for you to stop thinking about alcohol? 
0 
1 
2 
3  
2. Is it more important for you to keep drinking than to eat? 
0 
1 
2 
3  
3. Are you planning your day according to when and where you 
can drink? 
0 
1 
2 
3  
4. Do you drink in the morning, in the afternoon and in the 
evening? 
0 
1 
2 
3  
5. Do you drink to achieve a certain effect, without caring about 
what you drink? 
0 
1 
2 
3  
6. Do you drink as much as you want without taking into 
account what to do the next day? 
0 
1 
2 
3  
7. Would you drink too much even though you know that many 
problems are caused by alcohol? 
0 
1 
2 
3  
8. Do you know that it is impossible for you to stop drinking 
once you have started? 
0 
1 
2 
3  
9. Are you trying to control your drinking by quitting altogether 
for a few days or weeks at a time? 
0 
1 
2 
3 
10. Do you need a restorer to get started in the morning after an 
evening when you have been drinking a lot? 
0 
1 
2 
3 
11. Do your hands shake so that others can see it after an 
evening when you have drunk a lot? 
0 
1 
2 
3 
12. Do you wake up and vomit after drinking a lot? 
0 
1 
2 
3 
13. Do you try to avoid other people in the morning after an 
evening when you have drunk a lot? 
0 
1 
2 
3 
14. After drinking heavily, do you then see scary things that you 
then discover were just imagination? 
0 
1 
2 
3 

 
 
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15. Does it happen that after drinking you do not remember 
what happened? 
0 
1 
2 
3 
Raistrick, D., Dunbar, G., & Davidson, R., (1983). Development of a questionnaire to measure alcohol dependence. British Journal of the Addiction, 78, 89-95. 

 
 
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Bilaga C 
Alkoholkalender för Time Line Follow Back 
 

 
 
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Bilaga D  
 

 
 
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Bilaga E 
 

 
 
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Bilaga F 
 
 
Har andra än du själv påverkat ditt beslut att söka hjälp för dina alkoholproblem?  
  Ja, i hög grad 
 Till viss del 
 Inte alls 
 
Vem har påverkat dig? Max 2 alternativ 
 Anhörig 
 Arbetsgivare 
 Kriminalvården 
 Socialtjänsten 
 Annan_____________________________________ 
 
 
Om målet är att minska alkoholkonsumtionen ange målnivå 
ex. max antal standardglas per dag eller vecka:  
__________________________________ 

 
 
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Bilaga G 
 

 
 
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