Best Assessment of Sore Throat and Antibiotic Prescribing
Phase: NA
Conditions: Pharyngitis
Sponsor: Vastra Gotaland Region

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CLINICAL INVESTIGATION PLAN 
 
Best Assessment of Sore Throat and Antibiotic 
prescribing (BASTA) 
Version 1.1 dated 2023-03-17 
 
 
 
Principal Investigator: 
Ronny Gunnarsson MD PhD 
Professor in General Practice, School of Public Health and Community Medicine, 
Institute of Medicine, Gothenburg University 
Box 453 405 30 Göteborg, Sweden 
 
 
Sponsor: 
Allmänmedicinskt Centrum, The Västra Götaland Region, and 
Institute of Medicine, University of Gothenburg 
 
 
 

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Synopsis 
Title: 
Best Assessment of Sore Throat and Antibiotic prescribing (BASTA) 
Aim: 
This project aims to investigate if an organisational change of patient 
flow away from medical practitioners can reduce unnecessary antibiotic 
prescribing in patients attending with a sore throat as the main 
complaint.  
Primary Objective: 
Will the proportion of patients attending for an uncomplicated acute 
sore throat being managed according to prevailing guidelines differ if the 
initial assessment is made by a medical practitioner, a trained nurse or a 
trained pharmacist? 
Secondary Objectives: 
1) What proportion of patients attending PHC centres or pharmacies are 
classified as apparently uncomplicated, potentially complicated or 
potentially critically ill? (see appendix 1)1)  
2) Will patient characteristics differ if the patient first appears to the 
medical practitioner, a trained nurse or a trained pharmacist? 
3) To what extent do patients attending Primary Health Care/Pharmacies 
due to an acute sore throat harbour the SARS-CoV-2 virus? 
Study Design: 
A pragmatic controlled clinical trial design with three study arms. A total 
of 12 primary health care centres and 12 Pharmacies will function as 
study sites. One primary health care centre and one Pharmacy will be 
paired to form one cluster. 12 clusters will be allocated to one of three 
study arms: 
a) Patients will be first assessed by General practitioner. 
b) Patients will be first assessed by Nurse. 
c) Patients will be first assessed by Pharmacist.  
Study Population: 
Patients aged ≥6 years of age contacting a primary health care centre or 
a Pharmacy with the main complaint being an acute sore throat will be 
asked for participation. 
Number of Subjects: 
Approximately 450 subjects will be included altogether. 
Eligibility Criteria: 
Patients contacting the PHC centre or nearby Pharmacy with the main 
complaint, being an acute sore throat will be asked to participate. 
Inclusion criteria 
• The patient is contacting/attending PHC centre or Pharmacy 
presenting with a sore throat as the main complaint. 
• Male or female, aged ≥6 years. 
• Fluent in Swedish (reading, writing, conversational) (applicable to 
caregivers/parents/guardians in case of children). 
• Mental state such that he or she can understand and give 
informed consent to participation in the study by signing the 
Information and Consent Form. 
• Provision of signed and dated Informed Consent Form. 
Exclusion criteria 
• The illness episode is classified as potentially complicated or 
potentially critically ill (see appendix 1) 

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• Presence of SARS‐CoV‐2 virus in a patient first appearing at the 
PHC in a cluster where the assessment is supposed to be done by 
the pharmacists. The patient will not be sent to the pharmacist in 
case of presence of SARS-CoV-2-virus. 
• Patient request to be withdrawn from the study. 
Study Period: 
Jan 2023 – December 2025 
Sponsor: 
Allmänmedicinskt Centrum, The Västra Götaland Region, Sweden and 
Institute of Medicine, University of Gothenburg 
Clinical Investigation 
Plan authors: 
Principal Investigator: Ronny Gunnarsson, MD PhD, Professor in General 
Practice 
 
Trial Manager: Carl Wikberg, Reg nurse and PhD 
 
Pär-Daniel Sundvall, MD PhD 
Researcher and General Practitioner 
 
Tove Hedenrud 
Researcher, Pharmacist and Professor in Community Pharmacy 
 
Patrycja Woldan-Gradalska 
Medical Practitioner and PhD-Student 
 
Erik Wiezell 
Medical Practitioner and PhD-Student 
Funders: 
The Västra Götaland Region and University of Gothenburg 
Principal Investigator: 
Ronny Gunnarsson MD PhD 
Professor in General Practice 
School of Public Health and Community Medicine, Institute of Medicine 
Gothenburg University 
Box 454 
405 30 Gothenburg 
Sweden 
Version number and 
date: 
Version 1.1 dated 2023-03-17 
Investigation sites: 
12 Primary Health Care Centres in the region of Västra Götaland 
12 Pharmacies in the region of Västra Götaland 
Identification number 
of the clinical 
investigation: 
Universal Trial Number (UTN): U1111-1278-6025 
ClinicalTrials.gov Identifier: TBA 
CIP code: BASTA 

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Changes to the clinical investigation plan 
 
 
 
Date 
Changes 
2022-06-23 
Version 1.0 
Initial version 
2023-03-17 
Version 1.1 
Change 1: The previous version of Appendix 1 in this clinical investigation 
plan was inspired by ongoing discussions between researchers from 
different countries. These discussions has since been slightly refined and 
resulted in a published paper 
(https://doi.org/10.1080/23744235.2023.2191714). Hence, the table in 
Appendix 1 stating the differences between apparently uncomplicated, 
potentially complicated and potentially critical illness had a minor 
revision to make some clarifications and two new figures taken from the 
now published manuscript is added. The new figure 2 is revised 
compared to the published manuscript in that the wait-and-see policy 
for patients with an apparently uncomplicated acute sore throat and 3-4 
Centor criteria was removed to make figure 2 to comply exactly with the 
current Swedish national guidelines for managing patients with an acute 
sore throat. 
 
Change 2: More than 50% of pharmacies do not have space allocated 
making physical examination of patients possible. Hence, the pharmacies 
having this space has to be allocated to the arm where patients are 
assessed by pharmacists while the other pharmacies have to be 
allocated to one of the other two arms. This means we have to eliminate 
the random allocation of pharmacies to arms. This resulted in minor 
changes throughout the clinical investigation plan. 
 
Change 3: End of study is extended from June 2025 to December 2025. 

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Protocol Agreement 
 
I have read the protocol specified below. In my formal capacity as Investigator, my duties 
include ensuring the safety of the study subjects enrolled under my supervision and providing 
the sponsors with complete and timely information, as outlined in the protocol. It is 
understood that all information pertaining to the study will be held strictly confidential and 
that this confidentiality requirement applies to all study staff at this site. Furthermore, on 
behalf of the study staff and myself, I agree to maintain the procedures required to carry out 
the study in accordance with accepted GCP principles and to abide by the terms of this 
protocol. 
 
Protocol Title:  Best Assessment of Sore Throat and Antibiotic prescribing (BASTA) 
Protocol Number: 1.1 
Protocol Date: 2023-03-17 
 
 
 
 
Investigator Signature  
 
Date 
Ronny Gunnarsson, Professor in General Practice 

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Table of Contents 
1 
List of Abbreviations ......................................................................................................................... 9 
2 
Introduction ...................................................................................................................................... 9 
2.1 
Antibiotic stewardship ...................................................................................................................... 9 
2.2 
Antibiotic stewardship interventions ............................................................................................... 9 
2.3 
Current management of patients attending with an acute uncomplicated sore throat ............... 10 
2.4 
COVID-19 ........................................................................................................................................ 10 
2.5 
The remaining unresolved problem ............................................................................................... 10 
2.6 
Rationale and justification of study ................................................................................................ 10 
2.7 
A risk/benefit assessment and ethical considerations ................................................................... 11 
3 
Aims and objectives ........................................................................................................................ 11 
3.1 
Primary objective ............................................................................................................................ 11 
3.2 
Secondary objectives ...................................................................................................................... 11 
4 
Methods and study procedures ..................................................................................................... 11 
4.1 
Study design ................................................................................................................................... 11 
4.2 
Setting ............................................................................................................................................. 11 
4.3 
Allocation ........................................................................................................................................ 11 
4.4 
Study population and selection criteria ......................................................................................... 12 
4.4.1 Pre-screening and recruitment methods ....................................................................................... 12 
4.4.2 Consenting subjects ........................................................................................................................ 12 
4.4.3 Screening and eligibility criteria ..................................................................................................... 12 
4.4.4 Inclusion Criteria ............................................................................................................................. 12 
4.4.5 Exclusion criteria ............................................................................................................................. 13 
4.5 
Study Assessments ......................................................................................................................... 13 
4.5.1 Inclusion (Day 0) ............................................................................................................................. 13 
4.5.2 Follow-up ........................................................................................................................................ 15 
4.5.3 Collection of POCT test ................................................................................................................... 15 
4.6 
Management of suspected or confirmed COVID-19 cases ............................................................. 15 
4.7 
Early Termination and withdrawal of subjects ............................................................................... 15 
5 
Data collection and Data Management .......................................................................................... 15 
5.1 
Case Report Forms (CRF) ................................................................................................................ 15 
5.2 
Data management of personal data ............................................................................................... 16 
5.3 
Data Processor ................................................................................................................................ 16 
5.4 
Data Controller ............................................................................................................................... 16 
5.5 
Training the investigation team on the data management plan .................................................... 16 
5.6 
Procedures used for data review and database cleaning .............................................................. 16 

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5.7 
Procedures for verification and securing of electronic clinical data systems ................................ 16 
5.8 
Procedures for data retention ........................................................................................................ 16 
6 
Statistics and data analysis ............................................................................................................. 17 
6.1 
Sample size calculation ................................................................................................................... 17 
6.2 
Pre-existing Medical Conditions ..................................................................................................... 17 
7 
Trial management and oversight arrangements ............................................................................ 17 
7.1 
Project Management Group ........................................................................................................... 17 
7.2 
Inspection of records ...................................................................................................................... 18 
8 
Statements of compliance .............................................................................................................. 18 
8.1 
Approvals before commencement of clinical investigation ........................................................... 18 
9 
Investigator responsibilities............................................................................................................ 18 
9.1 
Clinical investigational plan amendments ...................................................................................... 18 
9.2 
Informed Consent ........................................................................................................................... 18 
9.3 
Study Site Staff................................................................................................................................ 19 
10 
Data recording and confidentiality ................................................................................................. 19 
10.1 
Data Protection............................................................................................................................... 19 
11 
Deviations from Clinical Investigational Plan ................................................................................. 19 
11.1 
Procedures for recording, reporting and analysing CIP deviations ................................................ 19 
11.2 
Notification requirements and time frames ................................................................................... 19 
11.3 
Disqualification of a clinical investigator ........................................................................................ 20 
12 
Serious breach requirements ......................................................................................................... 20 
13 
Study record retention ................................................................................................................... 20 
14 
Insurance and indemnity ................................................................................................................ 20 
15 
Renumeration ................................................................................................................................. 20 
15.1 
Renumeration to participating clinics ............................................................................................ 20 
15.2 
Renumeration to participating patients ......................................................................................... 21 
16 
End of study, reporting, publications and notification of results ................................................... 21 
16.1 
End of Study .................................................................................................................................... 21 
16.2 
Suspension or premature termination of the clinical investigation ............................................... 21 
16.3 
Authorship policy ............................................................................................................................ 21 
16.4 
Registration in a publicly accessible database ............................................................................... 21 
16.5 
Publication ...................................................................................................................................... 21 
17 
Expected outcome .......................................................................................................................... 22 
18 
Conflict of interest .......................................................................................................................... 22 
19 
References ...................................................................................................................................... 22 
20 
Description of appendices .............................................................................................................. 24 

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20.1 
Appendix 1 – Criteria for estimating illness severity ...................................................................... 25 
20.2 
Appendix 2 - Follow-up Questionnaire ........................................................................................... 30 
20.3 
Appendix 3 – eCRF .......................................................................................................................... 31 
20.4 
Appendix 4 – Payment of remuneration to included participants ................................................. 34 
 
 
 
 
 

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1 List of Abbreviations 
 
ARTI 
Acute Respiratory Tract Infection 
CIP 
Clinical Investigation Plan 
COVID‐19 
Coronavirus Disease that emerged 2019 
eCRF 
electronic Case Report Form 
GAS  
Group A Streptococci 
ICF 
Informed Consent Form 
ISF 
Investigator Site File 
PHC 
Primary Health Care 
PI 
Principal Investigator 
PMG 
Project Management Group 
SIC 
Subject Identification Code 
 
 
 
2 Introduction 
A sore throat is one of the common reasons people attend primary health care (PHC).[1] It is a 
special kind of acute upper respiratory tract infection (ARTI) commonly caused by various viruses 
and group A beta-haemolytic Streptococci (GAS). A viral origin should not be treated with 
antibiotics. However, the opinions on antibiotic use when the cause is GAS varies [2]. 
2.1 Antibiotic stewardship 
ARTI is the most common cause for antibiotic prescribing in PHC [3] with an overprescribing of 
2-4 times compared to guidelines.[4] Growing use of antibiotics is nowadays one of the biggest 
public health challenges, which require immediate action to prevent antibiotic resistance. 
Guidelines aim to reduce antibiotic prescribing for uncomplicated ARTI and may theoretically 
be beneficial but they have a tendency to work less well in PHC.[5] It has been challenging to 
implement the required organizational and behavioural changes needed into the clinical praxis of 
PHC. Inadequate time, resources and support are common factors explaining the lack of 
success.[6] The main problem seen is that guidelines are ignored by many medical practitioners 
who instead develop their own unique behaviour of antibiotic prescribing that does not resemble 
any guideline.[7, 8, 9] 
2.2 Antibiotic stewardship interventions 
A multitude of interventions has been done to change medical practitioners’ prescribing of 
antibiotics. Some of these studies show a modest short-term benefit[10] but it seems difficult to 
prove that any of the attempts so far has any long term benefit.[10] 
A possible alternative is to let other health care providers than medical practitioners manage 
otherwise healthy patients at their first visit for an uncomplicated acute sore throat. These patients 
are already today initially screened by not only medical practitioners, but also nurses and 
pharmacists. Studies evaluating nurse’s management of patients with sore throat are, due to 
methodological problems, inconclusive. A study by Thornley et al[11] tested the outcome of 

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letting community Pharmacies manage patients with an uncomplicated acute sore throat. The 
pharmacists aimed to adhere to a guideline identical to the current Swedish guideline and managed 
to prescribe antibiotics to only 9.8% of patients, which is much less compared to the prescribing 
pattern of medical practitioners. However, it is unclear if these patients had a milder illness 
compared to those seen by medical practitioners. 
2.3 Current management of patients attending with an acute 
uncomplicated sore throat 
Today patients appear either at a PHC centre or at the Pharmacy. The Pharmacy may provide 
advice on analgesic or refer the patient to a PHC centre. At the PHC centre, the patient may first 
appear to the medical practitioner or a nurse pending on local routines. The current Swedish 
guideline recommends no antibiotics and no testing for patients with 0-2 Centor criteria. For 
patients with 3-4 Centor criteria the guideline recommends testing and only consider antibiotics if 
GAS is present. 
2.4 COVID-19 
Key symptoms associated with COVID‐19 include cough, fever, headache, breathlessness and loss 
of sense of smell and taste.[12] A sore throat, which can be an early sign of the disease, is a less 
known symptom of COVID-19. However, 5-17% of patients with COVID-19 will experience a 
sore throat[13, 14] and attend their local PHC centres and Pharmacies. 
2.5 The remaining unresolved problem 
COVID-19 has gradually transformed from expressing itself as a severe lower respiratory tract 
infection to be more of an upper respiratory tract infection. Furthermore, COVID-19 is likely to 
transform from a pandemic to an endemic state with a low continuous incidence. Hence, in 
response to COVID-19 it seems crucial to identify to what extent the common sore throat is caused 
by the SARS-CoV-2. 
Furthermore, a large controlled clinical trial is required to sort out if patients attending with a sore 
throat as the main complaint are best managed by medical practitioners, nurses or pharmacists. 
This study aims to perform such a controlled clinical trial comparing the outcome of sore throat 
patients management by medical practitioner, nurses and pharmacists. This study also aims to 
investigate to what extent the SARS-CoV-2 virus is identified in these patients. 
2.6 Rationale and justification of study 
Antibiotic prescribing in PHC is influenced by the following factors: 
1) The patient propensity to visit a medical practitioner when ill. This is partly a personality 
factor[15] and partly influenced by competing, more or less accurate, information available 
from the government, friends, relatives, the press and on the Internet. 
2) The degree of access to an appointment with a medical practitioner. The number of doctors 
is increasing both in absolute numbers and on a per capita basis in most high-income 
countries.[16] However, this is a double edged sword. There is a correlation between 
attendance rates and antibiotic prescribing[3, 4] so lowering the threshold to see a medical 
practitioner is likely to increase antibiotic prescribing. 
3) The threshold for the medical practitioner the patient encounter to prescribe antibiotics. 
This vary due to different perceptions and personal preference[17] and can be labelled as 
the doctor risk factor. 

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4) The actual health of the patient with symptoms and signs. This may be a less important 
factor in the decision to prescribe antibiotics. 
Overprescribing of antibiotics suggests our health care system is a risk factor for population health. 
Several high-income countries have failed in addressing the issue of overuse of antibiotics.[16] 
Although Sweden has so far been more successful than most other high-income countries in its 
use of antibiotics[16], there is scope for further improvements.[4] The “low hanging fruit” for the 
health care system is to review and eliminate unnecessary use of antibiotics, especially in PHC.  
2.7 A risk/benefit assessment and ethical considerations 
The study will be approved by the Swedish Ethical Review Authority before recruiting study 
subjects. All subjects included in the study will sign an informed consent form. 
Participants are not expected to have any short-term health benefits from participating in the 
proposed study. Potentially, in the long term, participants might contribute to the implementation 
of new and enhanced antibiotic stewardship in health care. 
3 Aims and objectives 
3.1 Primary objective 
Will the proportion of patients attending for an uncomplicated acute sore throat being managed 
according to prevailing guidelines differ if the initial assessment is made by a medical 
practitioner, a trained nurse or a trained pharmacist? 
3.2 Secondary objectives 
1) What proportion of patients attending PHC centres or pharmacies are classified as 
apparently uncomplicated, potentially complicated or potentially critically ill? (see 
appendix 1) 
2) Will patient characteristics differ if the patient first appears to the medical practitioner, a 
trained nurse or a trained pharmacist?  
3) To what extent do patients attending PHC/Pharmacies due to an acute sore throat harbor 
the SARS-CoV-2 virus? 
4 Methods and study procedures 
4.1 Study design 
This study is a pragmatic controlled clinical trial. The duration of this study for each subject will 
be a maximum of approximately 1 month from inclusion to follow-up assessment. 
4.2 Setting 
The study will be conducted at PHC centres and Pharmacies in region Västra Götaland, Sweden. 
A total of 12 PHC centres and 12 Pharmacies will function as study sites. One PHC centre and 
one Pharmacy will be paired to form one cluster. These two are located near each other.  
4.3 Allocation 
Invited PHC centres and Pharmacies will be allocated to one of three arms. Some pharmacies will 
have space to assess patients, and some won’t. PHC centres and pharmacies expressing a wish to 
participate will be given thorough study information by the trial manager (or a person delegated 

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this task by the trial manager). When three PHC centres and pharmacies have remaining interest 
where at least one of the pharmacies have the space to assess patients they will be allocated to one 
of three arms, either to study arm 1, 2 or 3. 
Arm 1: participants get allocated for first assessment by a medical practitioner  
Arm 2: participants patients get allocated for first assessment by a Nurse 
Arm 3: participants patients get allocated for first assessment by a Pharmacist 
It is our ambition to allocate in total 12 PHC centres and 12 pharmacies. 
4.4 Study population and selection criteria 
This study is aiming to include 450 eligible study participants, 150 participants per study arm. 
4.4.1 Pre-screening and recruitment methods 
Patients contacting the PHC centre or nearby Pharmacy with the main complaint being an acute 
sore throat will be asked to participate in the study. If they agree, they will be asked to answer a 
few control questions (pre-screening), to assure they are eligible for inclusion. Eligibility criteria 
are described in detail elsewhere.  
4.4.2 Consenting subjects 
Following approval from the Swedish Ethical Review Authority, and before any investigation 
related procedure, potential subjects will sign the Informed Consent Form (ICF). The subjects 
will be given time to read and understand the contents of the ICF. The subjects will also have the 
chance to ask any questions that may have emerged. Research nurses may be delegated to obtain 
informed consent. If a subject is younger than 18, informed consent will be sought from a 
parent/guardian. Since this research involves no more than minimal risk, the consent of one 
parent/guardian will be considered sufficient. 
4.4.3 Screening and eligibility criteria 
Only subjects who fulfill all inclusion criteria will be enrolled in the investigation. Once the ICF 
is signed, each subject will be allocated a Subject Identification Code (SIC). The SIC will be 
recorded in the electronic Case Report Form (eCRF) associated with each subject as well as in 
patient’s chart/medical history. A Screening and Enrolment Log, that identifies everyone who 
has been pre-screened, screened and enrolled in the clinical investigation, will be kept in the 
Investigator Site File (ISF). 
4.4.4 Inclusion Criteria 
To be eligible to participate in this study, an individual must meet all of the following criteria: 
1. The patient is contacting/attending PHC centre or Pharmacy presenting with a sore throat 
as the main complaint. 
2. Male or female, aged ≥6 years. 
3. Fluent in Swedish (reading, writing, conversational) (applicable to 
caregivers/parents/guardians in case of children). 
4. Mental state such that he or she can understand and give informed consent to 
participation in the study by signing the Information and Consent Form. 
5. Provision of signed and dated Informed Consent Form. 

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4.4.5 Exclusion criteria 
Patients fulfilling any single exclusion criteria will be withdrawn from the study. Any data obtained 
before the withdrawal will be kept and included in analysis. Exclusion criteria to be applied after 
inclusion: 
• 
The illness episode is classified as potentially complicated or potentially critically ill (see 
appendix 1) 
• 
Presence of SARS‐CoV‐2 virus in a patient first appearing at the PHC in a cluster where the 
assessment is supposed to be done by the pharmacists. The patient will not be sent to the 
pharmacist in case of presence of SARS-CoV-2-virus. 
• 
Patient request to be withdrawn from the study. 
4.5 Study Assessments 
4.5.1 Inclusion (Day 0) 
Eligible subjects will be referred and assessed according to the planned allocation arm for the 
cluster, i.e. Arm 1/Arm 2/Arm 3. According to the protocol a standard assessment of sore throat is 
followed by a throat swab in order to detect GAS as well as the SARS‐CoV‐2 virus. The subject’s 
body temperature will be measured with an ear thermometer and any previous intake of fever 
medication will be recorded in the eCRF. Assessment of the Centor criterium fever will be based 
on either of: 
1) subject’s body temperature measured at site  
2) patient history on subject’s body temperature measured at home  
3) patient history on a high probability of fever even if the temperature is not measured (e.g. 
sweating, chills and shivering, headache, muscle aches, general weakness). 
Testing for GAS as well as SARS‐CoV‐2 virus will be performed at the PHC centre in all 
participants regardless of investigator’s clinical decision concerning the need of a throat swab for 
further management.  
The informed consent process, assessment and throat swab is estimated to take approximately 15-
20 minutes. For safety reasons all participants who, according to their allocation, will be primarily 
assessed by either a nurse or pharmacist will also receive an additional final assessment conducted 
by a medical practitioner. Hence, a medical practitioner is making the final decision as to antibiotic 
prescribing. For details see Table 1 (next page). 
 
 

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Table 1. Study procedures at the different study arms. 
 
Arm 1 (primary assessment 
by medical practitioner) 
Arm 2 (primary assessment 
by Nurse) 
Arm 3 (primary assessment by 
Pharmacist) 
Patient first appear to medical practitioner 
1) Informed consent by 
medical practitioner 
1) Informed consent by 
medical practitioner 
1) Informed consent by medical 
practitioner 
2) Assessment by medical 
practitioner 
2) Assessment by nurse 
2) Throat swab (presence of SARS‐CoV‐
2 virus → staff is informed and patient is 
excluded) 
3) Throat swab (presence of 
SARS‐CoV‐2 virus → staff is 
informed) 
3) Throat swab (presence of 
SARS‐CoV‐2 virus → staff 
is informed) 
3) Assessment by medical practitioner 
(patient asked to conceal any information 
provided by the medical practitioner) 
4) Assessment again by 
medical practitioner if the 
medical practitioner requested 
a throat swab. 
4) Assessment again by 
nurse if the nurse requested 
a throat swab. 
4) Transfer PHC → Pharmacy 
 
5) Assessment by medical 
practitioner 
5) Assessment by pharmacist 
 
 
6) Assessment again by pharmacist if the 
pharmacist requested a throat swab* 
 
 
 
 
Patient first appear to the nurse at the PHC 
1) Informed consent by nurse 
1) Informed consent by 
nurse 
1) Informed consent by nurse 
2) Assessment by medical 
practitioner 
2) Assessment by nurse) 
2) Throat swab (presence of SARS‐CoV‐
2 virus → staff is informed and patient is 
excluded) 
3) Throat swab (presence of 
SARS‐CoV‐2 virus → staff is 
informed) 
3) Throat swab (presence of 
SARS‐CoV‐2 virus → staff 
is informed) 
3) Assessment by medical practitioner 
(patient asked to conceal any information 
provided by the medical practitioner) 
4) Assessment again by 
medical practitioner if the 
medical practitioner requested 
a throat swab. 
4) Assessment again by 
nurse if the nurse requested 
a throat swab. 
4) Transfer PHC → Pharmacist 
 
5) Assessment by medical 
practitioner 
5) Assessment by pharmacist 
 
 
6) Assessment again by pharmacist if the 
pharmacist requested a throat swab* 
 
 
 
 
Patient first appear at the Pharmacy 
1) Informed consent by 
pharmacist 
1) Informed consent by 
pharmacist 
1) Informed consent by pharmacist 
2) Transfer  
Pharmacy → PHC 
2) Transfer 
 Pharmacy → PHC 
2) Assessment by pharmacist 
3) Assessment by medical 
practitioner 
3) Assessment by nurse) 
3) Transfer Pharmacy → PHC 
4) Throat swab (presence of 
SARS‐CoV‐2 virus → staff is 
informed) 
4) Throat swab (presence of 
SARS‐CoV‐2 virus → staff 
is informed) 
4) Throat swab (presence of SARS‐CoV‐
2 virus → staff is informed) 
5) Assessment again by 
medical practitioner if the 
medical practitioner requested 
a throat swab. 
5) Assessment again by 
nurse if the nurse requested 
a throat swab. 
5) Assessment again by pharmacist if the 
pharmacist requested a throat swab* 
 
6) Assessment by medical 
practitioner 
6) Assessment by medical practitioner 
*pharmacist phone the PHC to obtain the test outcome and register a decision on management 
 
Indicates relocation of the participant from the Pharmacy to the PHC or from the PHC to the Pharmacy. 
 
Indicates assessment by a medical practitioner (every patient is assessed at least once by a medical practitioner). 
 

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4.5.2 Follow-up 
Approximately one month after inclusion, all participants who were assessed according to their 
allocation to study arms will be asked to fill out a Follow-up Questionnaire (Appendix 2). The 
subject will be either prompted by a text message (SMS) or an email or, alternatively, will be 
contacted via telephone, depending of the way of communication chosen by the subject on Day 0 
(Inclusion).  
4.5.3 Collection of POCT test 
For the purpose of this study each participating PHC centre will receive Abbott ID NOW Strep A, 
a small device which will be used for the detection of GAS as well as the SARS‐CoV‐2 virus. It 
is a CE approved, easy to use device which is in alignment with ordinary routines and standards 
at PHC. This device uses a nucleic acid test with LAMP technology which is an isothermal PCR 
(similar to ordinary PCR). The test has a >95% sensitivity and >95% specificity to detect GAS 
and SARS‐CoV‐2 virus in comparison to ordinary PCR [18]. The test takes up to eight minutes to 
analyze. Test result will be available to the Investigator on request. The result of testing as well as 
Investigator’s clinical decision concerning antibiotic treatment with justification will be recorded 
in the eCRF. Study personnel, responsible for collecting the swab tests, will undergo an onsite 
training session on how to run the test. 
4.6 Management of suspected or confirmed COVID-19 cases 
It is recommended to assume that every patient is potentially infected with a pathogen that could 
be transmitted to study personal or other patients. Attempts should be made to isolate all patients 
with suspected symptoms of any respiratory infection using remote office areas (separate waiting 
areas, separate entrance). For the direct patient interactions, personal protective equipment must 
be available including gloves, an apron, a surgical mask and a visor/goggles. 
The practitioner performing the final assessment at PHC is responsible for informing the 
pharmacist about potential exposure to SARS‐CoV‐2 virus if a study participant is tested 
positive for SARS‐CoV‐2 virus after being consented or assessed at a Pharmacy. 
4.7 Early Termination and withdrawal of subjects 
Subjects first presenting to medical practitioners or nurses at the PHC centre but allocated 
to Arm 3 (assessment at Pharmacist) and tested positive for SARS‐CoV‐2 virus at PHC will 
be withdrawn from the study (Table 1). This group of participants will not be transferred to 
Pharmacy for assessment.  
Since the decision to take part in this study is entirely voluntary the subject is free to withdraw 
from the study at any time and for any reason, without the need to justify their decision. However, 
the Investigator should record the reason for the patient’s withdrawal, if possible. If withdrawal 
occurs for other reasons than subject’s decision, the primary reason for withdrawal will be 
documented in the eCRF. 
5 Data collection and Data Management 
5.1 Case Report Forms (CRF) 
Electronic Case Report Forms (eCRF), provided by REDCap consortium, will be used for data 
capture. Data will be collected at the following points: Screening and Inclusion (Day 0), Follow-
up (approximately Day 30), Early Termination and Withdrawal (alternatively). Data should be 
entered into the system timely after the patient has attended a visit or after the data become 

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available, as applicable. The Investigator will approve the eCRF entries for each patient with an 
electronic signature which is equivalent to a handwritten signature. The information entered in the 
eCRF is described in appendix 3. 
5.2 Data management of personal data 
The personal data collected in the electronic case report form (eCRF) is described in appendix 3. 
The study data managers, all working for the Sponsor, will have access to the data stored in the 
eCRF. Paper documentation containing personal data (i.e. signed Informed Consent Forms) will 
be stored at site in a locked cabinet or room within a secure area. Personal data stored electronically 
will only be accessible by authorized members of the study/clinical care team. A unique login 
name and password will be required to access electronic personal data. Personal data will be stored 
for at least 15 years. The Sponsor will be contacted before any paper documentation is destroyed. 
5.3 Data Processor 
The Data Processor is the Principal Investigator (PI). Processing of data may be delegated to a 
qualified member(s) of the research team. 
5.4 Data Controller 
The Data Controller is the study Sponsor. The Data Controller is the organization who 
determines the purposes for which, and the manner in which, any personal data are processed. 
5.5 Training the investigation team on the data management plan 
All members of the trial team, both management and clinical, will be informed and trained on the 
data management plan. 
5.6 Procedures used for data review and database cleaning 
After the trial database is declared clean and released for statistical analysis, a final copy of the 
database will be stored at the Sponsor. Errors occurring in the eCRF will be corrected 
electronically. 
5.7 Procedures for verification and securing of electronic clinical data 
systems 
To ensure an appropriate audit trail is present, the Investigator will make sure to maintain 
documentation that allows reconstruction of the course of events, that any and all data changes 
will be documented and that there will be no deletion of entered data. The revision history of all 
files and data will be maintained and repeatedly verified. A time-stamped electronic record that 
allows reconstruction of the course of events relating to the creation and modification of data will 
be created and maintained for this purpose. 
5.8 Procedures for data retention 
The PI and the Sponsor have agreed on policies and procedures that prevent unauthorized access 
to the data, both internally and externally. The PI will maintain a list of individuals who have 
access to the electronic data system as well as the dates of access and privileges granted to each 
user. This Data Access and Privileges List will be found in the Trial Master File (TMF). The 
signed Informed Consent Forms will be archived in clearly labelled and sealed plastic boxes 

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17 
 
stored in a locked cabinet located in a locked room. The labels will contain the CIP title, as well 
as the contact information of the PI. Data will be stored for at least 15 years. 
6 Statistics and data analysis 
The primary objective will be answered by comparing groups using a multivariable binary logistic 
mixed model analysis where cluster will be a random effect and group allocation a fixed effect. 
Patients age, gender and Centor score will be effect modifiers and treated as fixed effects. For the 
secondary objectives the following methods will be used: 
1 
Chi-square will be used to estimate any difference in illness severity between the arms. 
2 
Characteristics of patients, defined as age, gender, number of Centor criteria and presence of 
SARS-CoV-2 virus will be compared between the groups first attending a PHC centre or a 
Pharmacy using one way ANOVA (for age), Kruskal-Wallis test (for number of Centor 
criteria) and chi-square (for binary variables). 
3 
Chi-square will be used to estimate any difference in prevalence of SARS-CoV-2 virus 
between the arms 
6.1 Sample size calculation 
The primary hypothesis is that a primary assessment by pharmacists slightly more adhere to the 
desired guideline compared with assessments made by medical practitioners or nurses at PHC. A 
secondary, less likely, hypothesis is that nurses adhere better than medical practitioners to the 
desired guideline.  
A sample size calculation for the primary hypothesis assume that the proportion of patients 
correctly managed according to the desired guideline is 60% among patients primarily assessed 
at a PHC (by medical practitioners or nurses) and 80% if primarily assessed by pharmacists 
require 143 patients in each of these two groups when assuming a level of significance of 0.05 
and a power of 0.95. We aim to include 150 patients in each of our three groups, in total 450 
patients. 
6.2 Pre-existing Medical Conditions 
Pre-existing medical conditions (i.e. existed prior to informed consent) will not be asked for nor 
registered. 
7 Trial management and oversight arrangements 
7.1 Project Management Group 
The trial will be coordinated by a Project Management Group (PMG), consisting of the PI, prof. 
Ronny Gunnarsson, MD PhD, the Trial Manager (Carl Wikberg), a. prof. Pär-Daniel Sundvall and 
dr Patrycja Woldan-Gradalska. The Trial Manager will oversee the study and will be accountable 
to the PI. The Trial Manager will be responsible for checking the CRFs for completeness, 
plausibility and consistency. Any queries will be resolved by the Investigator or delegated member 
of the trial team. A Delegation Log will be prepared for the investigation site, detailing the 
responsibilities of each member of staff working on the trial. 

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7.2 Inspection of records 
Investigators and institutions involved in the study will permit trial related audits on behalf of the 
Sponsor and regulatory inspection(s). In the event of an audit, the Investigator agrees to allow the 
representatives of the Sponsor direct access to all study records and source documentation. In the 
event of regulatory inspection, the Investigator agrees to allow inspectors direct access to all study 
records and source documentation. 
8 Statements of compliance 
Good Clinical Practice (GCP) is the ethical and practical standard to which all clinical research is 
conducted. The GCP guidelines were developed by the International Conference on Harmonisation 
(ICH) and are applicable to the conduct of all research including clinical trials which do not involve 
an Investigational Medicinal Product. The Investigator will ensure that this trial is conducted in 
accordance with relevant regulations and with Good Clinical Practice. 
8.1 Approvals before commencement of clinical investigation 
The clinical investigation shall not begin until the required approval/favourable opinion from the 
Swedish Ethics Review Authority have been obtained. Any additional requirements imposed by 
the Swedish Ethics Review Authority shall be followed, if appropriate. 
9 Investigator responsibilities 
The Investigator is responsible for the overall conduct of the study at the site and compliance with 
the CIP and any Clinical Investigational Plan Amendments. Responsibilities may be delegated to 
an appropriate member of study site staff.  
9.1 Clinical investigational plan amendments 
Any changes in research activity, except those necessary to remove an apparent, immediate hazard 
to the subject in the case of an urgent safety measure, must be reviewed and approved by the PI. 
The updated CIP will be signed by the Investigator(s) and the Sponsor. Amendments will be 
notified to (non-substantial amendments) or approved by the Swedish Ethics Review Authority 
before the implementation. 
9.2 Informed Consent 
The Investigator is responsible for ensuring informed consent is obtained before any study specific 
procedures are carried out. The decision of a subject to participate in clinical research is voluntary 
and should be based on a clear understanding of what is involved. Subjects must receive adequate 
oral and written information – appropriate Subject Information and Informed Consent Forms (ICF) 
will be provided. The oral explanation to the subject will be performed by the Investigator or 
qualified delegated person and must cover all the elements specified in the Subject Information 
and Consent Form. The subject must be given every opportunity to clarify any points they do not 
understand and, if necessary, ask for more information. The subject must be given sufficient time 
to consider the information provided. It should be emphasized that the subject may withdraw their 
consent to participate at any time without loss of benefits to which they otherwise would be 
entitled. The Investigator or delegated member of the trial team and the subject will sign and date 

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the ICF(s) to confirm that consent has been obtained. The subject will receive a copy of this 
document and a copy will be filed in the ISF. 
9.3 Study Site Staff 
The Investigator must be familiar with the CIP and the study requirements. It is the Investigator’s 
responsibility to ensure that all staff assisting with the study are adequately informed and trained 
about the CIP and their trial related duties. 
10 Data recording and confidentiality 
The Trial Manager is responsible for the quality of the data recorded in the eCRF at each study 
site. The PI will ensure that the required documentation is available in local ISFs. All evaluation 
forms, reports, and other records must be identified in a manner designed to maintain subject 
confidentiality. All records must be kept in a secure storage area with limited access. Clinical 
information will not be released without the written permission of the subject. The Investigator 
and study site staff involved with this study may not disclose or use for any purpose other than 
performance of the study, any data, record, or other unpublished, confidential information 
disclosed to those individuals for the purpose of the study. Prior written agreement from the 
Sponsor or its designee must be obtained for the disclosure of any said confidential information to 
other parties. 
10.1 Data Protection 
All Investigators and study site staff involved with this study must comply with the requirements 
of the appropriate data protection legislation (including the General Data Protection Regulation 
and Data Protection Act) with regard to the collection, storage, processing and disclosure of 
personal information. Access to collated subject data will be restricted to those individuals from 
the research team treating the subjects, representatives of the Sponsor and representatives of 
regulatory authorities. Computers used to collate the data will have limited access measures via 
usernames and passwords. Published results will not contain any personal data that could allow 
identification of individual subjects. 
11 Deviations from Clinical Investigational Plan 
Any change, divergence, or departure from the study design or procedures defined in the CIP is 
considered a deviation. The investigator shall not deviate from this CIP except in situations that 
affect the subject’s rights, safety and well-being, or the scientific integrity of the clinical 
investigation. 
11.1 Procedures for recording, reporting and analysing CIP deviations 
CIP deviations will be recorded in a deviation log maintained by the study site. Any deviations 
from the CIP that are identified will be reported to the Sponsor within 24 hours of being identified. 
11.2 Notification requirements and time frames 
Requests for deviations by the Investigator will be responded to within 48 hours of receipt. The 
Corrective and Preventive Action (CAPA) document will be created for every deviation. The 

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CAPA will focus both on the immediate noncompliance and the broader scope of the problem. It 
involves investigating and understanding the issue, correcting the issue, and preventing the root 
cause. The CAPA will describe reactive steps to correct the immediate problem (corrective), 
describe the measures taken to understand and underlying cause(s) and extent of the problem(s) 
and list proactive steps to prevent future recurrence of the problem(s) (preventive). The PI, in 
collaboration with the PMG and study site staff, will strive to develop effective corrective and 
preventive actions focusing on eliminating the cause of the detected deviation.  
11.3 Disqualification of a clinical investigator 
The Investigator is disqualified if the Investigator has repeatedly or deliberately deviated from the 
CIP, or failed to comply with applicable regulatory requirements, or has repeatedly or deliberately 
submitted false information to the Sponsor, or the Swedish Ethics Review Authority, in any 
required report. 
12 Serious breach requirements 
A serious breach is a breach which is likely to affect to a significant degree: 
1) the safety or physical or mental integrity of the subjects of the trial; or 
2) the scientific value of the study. 
If a potential serious breach is identified by the Investigator or delegates, the Sponsor must be 
notified within 24 hours. It is the responsibility of the Sponsor to assess the impact of the breach 
on the scientific value of the trial, to determine whether the incident constitutes a serious breach 
and report to the Swedish Ethics Review Authority as necessary. 
13 Study record retention 
All study documentation will be kept for a minimum of 15 years from the end of study point 
defined in the CIP. When the minimum retention period has elapsed, study documentation will not 
be destroyed without permission from the Sponsor. Following publications, a de-identified 
individual subject data set will be submitted for public data archiving for sharing purposes. 
14 Insurance and indemnity 
The Clinical investigational plan has been designed by the PI and researchers employed by the 
Västra Götaland Region and collaborators. All patients will meet a medical practitioner. Hence, 
the national “Patientskadeförsäkringen” is valid for this study. 
15 Renumeration 
15.1 Renumeration to participating clinics 
Participating PHC centres as well as pharmacies are paid for their job as follows: 
• Inform patient about the study and obtain informed consent: 300 SEK. 
• Doing the first assessment of the patient and propose management: 400 SEK. 

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• Obtain the throat swab and perform laboratory analysis: 300 SEK (test apparatus and test 
kits are supplied by the sponsor). 
• Doing the final assessment by a medical practitioner and deciding about management: 400 
SEK (for patients allocated to do their first assessment by a medical practitioner the first 
assessment and the final assessment will be the same and together result in a renumeration 
of 400 SEK). 
15.2 Renumeration to participating patients 
All participants included in the study will have a longer physical visit than they excepted. A throat 
swab will be taken on all patients, even when it is not motivated by current guidelines. 
Furthermore, they are required to answer a short survey 30 days after the first visit. All participants 
will be offered a small renumeration of 300 SEK for the extra time they have to put in and for the 
discomfort of obtaining a throat swab sample. Parents / guardians will decide if the renumeration 
goes to their child or to themselves (not all children have own bank accounts). Information about 
renumeration is included in the patient information for adults and older children. For young 
children this information is not included in the written information but will be passed on verbally 
to their guardian. 
16 End of study, reporting, publications and notification of results 
16.1 End of Study 
The end of study is defined as when all data for the follow-up at 30 days after the visit is collected. 
The Investigators or the Sponsor also have the right at any time to terminate the study for clinical 
or administrative reasons. 
16.2 Suspension or premature termination of the clinical investigation 
Both the Sponsor and the PI reserve the right to terminate the clinical investigation at any time. 
Should this be necessary, the procedures will be arranged on an individual basis after review and 
consultation by both parties. In terminating the clinical investigation, the Sponsor and the PI will 
assure that adequate consideration is given to the protection of the subject’s interests. 
16.3 Authorship policy 
Ownership of the data arising from this study resides with the study team. On completion of the 
study, the study data will be analysed and tabulated, and a clinical study report will be prepared in 
accordance with university guidelines. 
16.4 Registration in a publicly accessible database 
In accordance with the Declaration of Helsinki, this research will be registered in a publicly 
accessible database before recruitment of the first subject. 
16.5 Publication 
The Clinical Study Report (CSR) will be submitted to the Sponsor within 1 year of the end of the 
study. Where acceptable, a published journal article may be submitted as the CSR. The clinical 
study report may be used for publication and presentation at scientific meetings. Investigators have 
the right to publish orally or in writing the results of the study. All proposed publications and 
presentations must be discussed with the PI prior to their release. Summaries of results will also 

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22 
 
be made available to Investigators. The data will be disseminated at local, national level via 
publication in peer review journals and at international meetings. Results, links to study outputs 
and a general summary of the results will be available for the public. The study report will undergo 
independent peer review prior to publication in a scientific Journal. 
17 Expected outcome 
Previous studies suggests that pharmacists may reduce antibiotic prescribing by up to 50%. 
However, this has not been investigated in any high-quality study. We do expect that pharmacists 
will recommend less antibiotic prescribing than medical practitioners and most likely adhere better 
to national guidelines. 
18 Conflict of interest 
No conflict of interest to declare. 
19 References 
1. 
Finley CR, Chan DS, Garrison S, et al. What are the most common conditions in primary 
care? Systematic review. Can Fam Physician. 2018 Nov;64(11):832-840. PubMed PMID: 
30429181; PubMed Central PMCID: PMCPMC6234945. eng. 
2. 
Gunnarsson R, Ebell MH, Wächtler H, et al. Association between guidelines and medical 
practitioners' perception of best management for patients attending with an apparently 
uncomplicated acute sore throat: a cross-sectional survey in five countries. BMJ Open. 2020 
Sep 17;10(9):e037884. doi: 10.1136/bmjopen-2020-037884. PubMed PMID: 32948565; 
PubMed Central PMCID: PMCPMC7500311. eng. 
3. 
Quality in antibiotic prescribing in primary care. Current practice, relation to guidelines and 
antimicrobial 
resistance. 
[Internet]. 
2017. 
Available 
from: 
https://portal.research.lu.se/portal/files/32280748/Minus_IV_e_spik_Mia_T.pdf. 
4. 
Tyrstrup M, van der Velden A, Engstrom S, et al. Antibiotic prescribing in relation to 
diagnoses and consultation rates in Belgium, the Netherlands and Sweden: use of European 
quality 
indicators. 
Scand 
J 
Prim 
Health 
Care. 
2017 
Mar;35(1):10-18. 
doi: 
10.1080/02813432.2017.1288680. PubMed PMID: 28277045; PubMed Central PMCID: 
PMCPMC5361413. 
5. 
Tyrstrup M, Andre M, Brorsson A, et al. A study of guidelines for respiratory tract infections 
and their references from Swedish GPs: a qualitative analysis. Scand J Prim Health Care. 
2020 Mar;38(1):83-91. doi: 10.1080/02813432.2020.1717073. PubMed PMID: 32031035; 
PubMed Central PMCID: PMCPMC7054917. 
6. 
Flottorp S, Havelsrud K, Oxman AD. Process evaluation of a cluster randomized trial of 
tailored interventions to implement guidelines in primary care--why is it so hard to change 
practice? Fam Pract. 2003 Jun;20(3):333-9. PubMed PMID: 12738704. 
7. 
Grondal H, Hedin K, Strandberg EL, et al. Near-patient tests and the clinical gaze in 
decision-making of Swedish GPs not following current guidelines for sore throat - a 
qualitative interview study. BMC Fam Pract. 2015 Jul 4;16:81. doi: 10.1186/s12875-015-
0285-y. PubMed PMID: 26141740; PubMed Central PMCID: PMCPMC4491276. 
8. 
Hedin K, Strandberg EL, Grondal H, et al. Management of patients with sore throats in 
relation to guidelines: an interview study in Sweden. Scand J Prim Health Care. 2014 
Dec;32(4):193-9. doi: 10.3109/02813432.2014.972046. PubMed PMID: 25363143; 
PubMed Central PMCID: PMCPMC4278394. 
9. 
Rico-Ferreira P, Palazon-Bru A, Calvo-Perez M, et al. Nonadherence to guidelines for 
prescribing antibiotic therapy to patients with tonsillitis or pharyngotonsillitis: a cross-

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23 
 
sectional 
study. 
Curr 
Med 
Res 
Opin. 
2015;31(7):1319-22. 
doi: 
10.1185/03007995.2015.1041896. PubMed PMID: 25876462. 
10. 
Coxeter P, Del Mar CB, McGregor L, et al. Interventions to facilitate shared decision making 
to address antibiotic use for acute respiratory infections in primary care. Cochrane Database 
Syst Rev. 2015 Nov 12;2015(11):Cd010907. doi: 10.1002/14651858.CD010907.pub2. 
PubMed PMID: 26560888; PubMed Central PMCID: PMCPMC6464273 declared Elaine M 
Beller: none declared Tammy Hoffmann: none declared. eng. 
11. 
Thornley T, Marshall G, Howard P, et al. A feasibility service evaluation of screening and 
treatment of group A streptococcal pharyngitis in community pharmacies. J Antimicrob 
Chemother. 2016 Nov;71(11):3293-3299. doi: 10.1093/jac/dkw264. PubMed PMID: 
27439523; PubMed Central PMCID: PMCPMC5079295. 
12. 
Pascarella G, Strumia A, Piliego C, et al. COVID-19 diagnosis and management: a 
comprehensive review. J Intern Med. 2020 Aug;288(2):192-206. doi: 10.1111/joim.13091. 
PubMed PMID: 32348588; PubMed Central PMCID: PMCPMC7267177. eng. 
13. 
Lovato A, de Filippis C. Clinical Presentation of COVID-19: A Systematic Review Focusing 
on Upper Airway Symptoms. Ear Nose Throat J. 2020 Nov;99(9):569-576. doi: 
10.1177/0145561320920762. PubMed PMID: 32283980; eng. 
14. 
Struyf T, Deeks JJ, Dinnes J, et al. Signs and symptoms to determine if a patient presenting 
in primary care or hospital outpatient settings has COVID-19 disease. Cochrane Database 
Syst Rev. 2020 Jul 7;7:CD013665. doi: 10.1002/14651858.CD013665. PubMed PMID: 
32633856; PubMed Central PMCID: PMCPMC7386785. 
15. 
André M, Hedin K, Håkansson A, et al. More physician consultations and antibiotic 
prescriptions in families with high concern about infectious illness--adequate response to 
infection-prone child or self-fulfilling prophecy? Fam Pract. 2007 Sep;24(4):302-7. doi: 
10.1093/fampra/cmm016. PubMed PMID: 17545203; eng. 
16. 
OECD EU. Health at a Glance: Europe 2020. State of Health in the EU Cycle [Internet]. 
Available 
from: 
https://www.oecd-ilibrary.org/docserver/82129230-
en.pdf?expires=1632494469&id=id&accname=guest&checksum=8275DE3EBC93583DB
6810DCF057E0379. 
17. 
Pitts J, Vincent S. What influences doctors' prescribing? Sore throats revisited. J R Coll Gen 
Pract. 1989 Feb;39(319):65-6. PubMed PMID: 2552095; PubMed Central PMCID: 
PMCPMC1711733. eng. 
18. 
Cohen DM, Russo ME, Jaggi P, et al. Multicenter Clinical Evaluation of the Novel Alere i 
Strep A Isothermal Nucleic Acid Amplification Test. J Clin Microbiol. 2015 Jul;53(7):2258-
61. doi: 10.1128/JCM.00490-15. PubMed PMID: 25972418; PubMed Central PMCID: 
PMCPMC4473182. 
 
 

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20 Description of appendices 
List of appendices: 
1) Appendix 1 – Criteria for estimating illness severity 
Contains criteria to classify the illness episode as one of  
a) apparently uncomplicated, 
b) potentially complicated, 
c) potentially critically ill. 
2) Appendix 2 - Follow-up Questionnaire 
The Follow-up Questionnaire is attached as a separate pdf-file. 
3) Appendix 3 - eCRF 
The content of the eCRF is described in a separate pdf-file 
4) Appendix 4 - Payment of remuneration to included participants 
Procedure and forms for paying remuneration to participants. 
 

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20.1 Appendix 1 – Criteria for estimating illness severity 
Any single item fulfilled in the rightmost column makes the patient “potentially critically ill” (Inspired by the NICE Sepsis guidelines from 2017). Similarly, any 
single item fulfilled in the orange column rules out that the patient is “apparently uncomplicated”. 
 
Apparently uncomplicated 
Potentially complicated 
Potentially critically ill 
 
===== History ===== 
Impaired immune system 
No 
Yes 
 
History of peritonsillar abscess 
No 
Yes 
 
Visits 
First visit 
Re-visiting health care 
for the same illness episode 
 
 
===== Acute symptoms from the throat ===== 
Worsening 
No worsening after day 3. 
Worsening after day 3. 
 
Total duration 
Duration <5 days OR 5-8 days with 
noticeable improvement the last 1-2 
days 
Duration ≥5 days without 
noticeable improvement OR 
duration ≥8 days 
(HIV or mononucleosis?) 
 
Intensity of pain 
Mild to moderate intensity or initially 
severe with very good effect of fast 
acting paracetamol 
Severe intensity and poor or 
moderate 
effect of paracetamol 
 
Location of pain 
Mainly bilateral 
Unilateral 
 
 
===== Acute symptoms from locations other than the throat ===== 
Neck stiffness and/or torticollis 
No 
No 
Yes 
Swelling of the face or neck 
No 
No 
Yes 
Chest pain 
No 
No 
Yes  
New altered mental state 
No 
No 
Yes 
Passing of urine 
Adults: Yes within 12 hours 
Adults: No urine in 12-17 hours 
Adults: No urine in ≥18 hours 
Inability to open the mouth fully 
No 
Yes 
 
Difficulty swallowing saliva, 
drooling 
No 
No 
Yes (epiglottitis?) 

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Severe local pain on neck, torso 
or extremities 
No 
No 
Yes (necrotizing fasciitis?) 
Abdominal symptoms 
No 
No 
Vomiting OR diarrhoea (toxins?) 
 
 
===== Physical examination ===== 
General appearance 
Mildly but not significantly affected 
Significantly affected 
 
Mottled or ashen appearance of 
skin OR Non-blanching rash 
No 
No 
Yes 
Red non-blanching skin rash that 
has a sandpaper feel or a 
“strawberry tongue” 
No 
Yes 
 
Rigors (severe shivering) 
No 
No 
Yes 
Cyanosis 
No 
No 
Yes on skin, lips or tongue 
Respiratory distress OR stridor 
No 
No 
Yes (epiglottitis) 
Very thick, gray membrane 
covering the throat and tonsils 
No 
No 
Yes (diphtheria?) 
Heart rate 
Children 3-5 years: <120 
Children 6-7 years: <110 
Children 8-11 years: <105 
All patients ≥ 12 years: ≤90 
Children 3-5 years: 120-129 
Children 6-7 years: 110-119 
Children 8-11 years: 105-114 
All patients ≥ 12 years: 91-130 
Children 3-4 years: sustained >140 
Children 5 years: >130 
Children 6-7 years: >120 
Children 8-11 years: >115 
All patients ≥ 12 years : >130 
Systolic blood pressure (mm Hg) 
All patients ≥ 12 years: > 100 
All patients ≥ 12 years: 91 - 100 
All patients ≥ 12 years: ≤90 mmHg OR 
≥40 mmHg below normal for the 
patient (if known) 
Respiratory rate 
Children 3-7 years: <24 
Children ≥ 8 years + adults: <21 
Children 3-5 years: 24-28 
Children 6-7 years: 24-26 
All patients ≥ 8 years: 21-24 
Children 3-5 years: ≥29 
Children 6-7 years: >27 
All patients ≥ 8 years: ≥25 
Body temperature (tympanic) 
≥36°C AND <39.5°C 
<36°C OR ≥39.5-41°C 
>41°C 
Oxygen saturation in room air (%) 
Children 6-12 years: ≥97% 
All patients ≥ 13 years: ≥96% 
Children 6-12 years: 95-96% 
All patients ≥ 13 years: 92-95% 
Children 6-12 years: <95 
All patients ≥ 13 years: <92% (<88% 
in COPD) 

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Potentially critically ill patients should be admitted to nearest hospital as soon as possible for further evaluation. Potentially complicated patients should not 
be included in the study but instead be referred to their medical practitioner for immediate assessment. Only patients whose illness episode is apparently 
uncomplicated are to be included in the study. 
Physical examination of patients that at first glance seem to have an apparently uncomplicated acute sore throat: 
Take history (including acute symptoms) and evaluate the general appearance of the patient. Do inspection of the throat, palpation of cervical glands and 
estimate body temperature. In the meantime, obtain oxygen saturation and the heart rate (to be done with the same device). No need to obtain blood 
pressure or respiratory rate if all these indicate an apparently uncomplicated illness episode. Practical instructions are provided in figure 1 and 2 below.

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Patient history - Any of: 
• 
Neck stiffness and/or torticollis 
• 
Swelling of the face or neck 
• 
Chest pain 
• 
New altered mental state 
• 
Difficulty swallowing saliva, drooling 
• 
Severe local pain on neck, torso or 
extremities 
• 
Vomiting or diarrhea 
• 
Rigors (severe shivering) 
• 
Difficulty breathing 
Patient history - Any of: 
• 
Impaired immune system  
• 
History of peritonsillar abscess 
• 
Contacting again for the same illness episode 
• 
Worsening day 3-5 
• 
Duration ≥5 days without noticeable 
improvement OR duration ≥8 days 
• 
Inability to open the mouth fully 
• 
Severe intensity of throat pain and no effect 
of paracetamol 
• 
Location of pain in the throat is unilateral 
• 
Adults: No passing of urine for ≥12 hours 
Patient history: New onset cough and describe 
their symptoms as mild or moderate. 
The patient is likely to have an 
apparently uncomplicated acute 
sore throat. 
Advise on the use of adequate 
dose of paracetamol and a 
recommendation to contact 
health care again if worse or if 
not better within 3 days. 
The patient is potentially 
critically ill. Discuss immediately 
with a physician and consider 
urgent referral to a hospital. 
The patients illness is potentially 
complicated. Arrange for a 
consultation with a physician as 
soon as possible. If that is not 
possible consider urgent referral 
to a hospital. 
Arrange for a consultation the same or the 
following day for physical examination and 
further management (see figure 2) 
Yes 
Yes 
Yes 
No 
No 
No 
Figure 1 – Initial triage of patients (can be done in a phone or video consultation) 

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Physical examination - Any of: 
• 
Mottled or ashen appearance of skin OR 
Non-blanching rash 
• 
Rigors (severe shivering) 
• 
Cyanosis on skin, lips or tongue 
• 
Respiratory distress OR stridor 
1) Put on a fingertip device to measure oxygen 
saturation and pulse 
2) Inspect the throat, palpate cervical glands 
3) Objectively estimate body temperature (ear 
thermometer may suffice) 
4) Decide on the number of Centor scores 
5) Record readings from the fingertip device 
Physical examination - Any of: 
• 
Tachycardia or low oxygen saturation 
• 
Systolic hypotension (only checked for if 
pulse or oxygen saturation are abnormal) 
(see table 3 for cut off values) 
• 
Red non-blanching skin rash that has a 
sandpaper feel or a “strawberry tongue” 
Ensure patient tested adequate 
dose of paracetamol. If that is 
not done administer rapid acting 
paracetamol at the clinic (will 
have an effect within 15-30 
minutes). 
The patient is potentially 
critically ill. Discuss immediately 
with a physician and consider 
urgent referral to a hospital. 
The patients illness is potentially 
complicated. Arrange for a 
consultation with a physician as 
soon as possible. If that is not 
possible consider urgent referral 
to a hospital. 
Centor score 3-4 
(McIsaac 3-4 or 
FeverPain 3-5) 
Yes 
Yes 
No 
No 
Figure 2 – Further assessment and management of patients  (requires a physical visit) 
Advise on the use of adequate dose of 
paracetamol and to contact health care again if 
worsening after day 3 or if total duration is ≥5 
days without noticeable improvement or a total 
duration of ≥8 days. 
Obtain a throat swab analysed 
on site for presence of GAS. 
Antibiotics may be considered if 
test is positive. 
Poor or moderate 
effect 
Very good 
effect 
The patient has an apparently uncomplicated 
acute sore throat 
Yes 
Centor score 0-2 
(McIsaac 0-2 or 
FeverPain 0-2) 

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20.2 Appendix 2 - Follow-up Questionnaire 
(The follow-up questionnaire is delivered either as an electronic survey prompted by a text message, 
as an email or a telephone interview pending on patients request. Only relevant questions are 
prompted. Hence, patients stating they have not attended any health care provider again for the 
same illness vill not see the subsequent questions.) 
(The follow-up questionnaire is is Swedish and is therefore omitted here. It can be requested from 
the principal investigator.) 
 
 

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20.3 Appendix 3 – eCRF 
An electronic case report form (eCRF) will be used containing the information below. The eCRF-
system will use the information to automatically evaluate if the patient fulfill the inclusion criteria or 
if the exclusion criteria illness severity is fulfilled. 
Inclusion criteria 
The patient is contacting/attending PHC centre or Pharmacy presenting with a sore throat as the 
main complaint 
Age (the eCRF will not accept patients <6 years) 
Fluent in Swedish (reading, writing, conversational) (applicable to caregivers/parents/guardians in 
case of children) (yes/no)? 
Mental state such that he or she can understand and give informed consent to participation in the 
study by signing the Information and Consent Form (yes/no)? 
Provision of signed and dated Informed Consent Form (yes/no)? 
 
Basic information 
Site where the patient first attends with a complaint of a sore throat 
Biological sex (male/female) 
Place of birth (in Sweden, in Europe but not Sweden, outside Europe) 
Preferred method for contact about the 30-day follow-up (phone or email is stored) 
 
Patient history 
Known impaired immune system (yes/no)? 
History of peritonsillar abscess (yes/no)? 
First visit for this illnes episode (yes/no)? 
Duration of the sore throat (days)? 
Noticable improvement in symptoms last 1-2 days? 
Intensity of pain in the throat (mild, moderate or severe)? 
Has taken over the counter analgetic medication in adequate dose (yes or no) 
Location of pain in the throat (unilateral or bilateral)? 
Presence of neck stiffness and/or torticollis (yes/no)? 
Swelling of the face or neck (yes/no)? 
Chest pain (yes/no)? 
New altered mental state (yes/no)? 
Passing of urine (hours since last time) 
Inability to fully open the mouth (yes/no) 
Difficulty swallowing saliva, drooling (yes/no)? 

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Severe local pain on neck, torso or extremities (yes/no)? 
Abdominal symptoms such as vomiting / diarrhoea (yes/no)? 
Used over the counter pain medication before arriving to the clinic? (yes/no)? 
Measured body temperature at home? (yes/no and if yes what was it) 
Cough during this illness episode (yes/no)? 
 
Patients general condition at assessment 
General appearance (unaffected, mildly affected or significantly affected) 
Mottled or ashen appearance of skin OR Non-blanching rash (yes/no)? 
Red non-blanching skin rash that has a sandpaper feel typical for scarlet fever (yes/no) 
Rigors (severe shivering) (yes/no)? 
Cyanosis (yes/no)? 
Respiratory distress OR stridor (yes/no)? 
Heart rate (beats/ minute) 
Oxygen saturation in room air (%) 
Tympanic body temperature (Celcius) 
 
Patients throat status at assessment 
Any tonsillar excudate (yes/no)? 
Very thick, gray membrane covering the throat and tonsils (yes/no)? 
Tender cervical lymph nodes (yes/no)? 
Presence of Strawberry tounge typical for scarlet fever (yes/no) 
 
Proposed evaluation and management (before any throat swab) 
Suspected aetiologic agent (viral/bacterial/unsure)? 
Your recommended management (No action/obtain a throat swab/prescribe antibiotics)? 
 
Outcome of throat swab analysis 
Presence of group A Streptococci (yes/no)? 
Presence of Sars-Cov-2 virus (yes/no)? 
 
Proposed management (after throat swab for those ordering it) 
Would you recommend antibiotics (yes/no?) 
 
 
 

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Final assessment by medical practitioner (only if primary assessment by nurse or pharmacist) 
Your recommended management (No action/prescribe antibiotics)? 
Was the outcome of the throat swab of any help? (yes/no) 
 
 
 

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20.4 Appendix 4 – Payment of remuneration to included participants 
Participants are asked to fill in a form with the information shown below to receive remuneration of 
SEK 300 (before tax). The research team sends the form to the finance department Regionhälsan, 
Västra Götalandsregionen who make the payment. The Swedish social security number is requirered 
on this form to enable payment of preliminary tax. The payment will be made after the 30-day 
follow-up questionnaire is completed.