Please be advised that due to the high volume of submissions, the ANZCTR is currently experiencing delays in processing submissions from those outside of Australia and New Zealand. As the ANZCTR is funded by Australia and New Zealand, we must prioritise submissions from these countries first. International submissions should allow additional time for registration. Apologies for any inconvenience caused.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial registered on ANZCTR


Registration number
ACTRN12616001240437
Ethics application status
Approved
Date submitted
31/08/2016
Date registered
6/09/2016
Date last updated
19/06/2019
Date data sharing statement initially provided
19/06/2019
Date results information initially provided
19/06/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
The Pharmacy Diabetes Screening Trial: a comparison of three community pharmacy based approaches to screening for type 2 diabetes on proportions of newly diagnosed type 2 diabetes cases.
Scientific title
The Pharmacy Diabetes Screening Trial compares the effectiveness and cost-effectiveness of three screening models for type 2 diabetes and diabetes risk in previously undiagnosed populations on rates of newly diagnosed cases; risk assessment alone; risk assessment plus point-of-care (POC) testing with either HbA1c or small capillary blood glucose test (scBGT).
Secondary ID [1] 290066 0
Nil
Universal Trial Number (UTN)
U1111-1187-0831
Trial acronym
Diabetes Screening PTP
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Type 2 Diabetes 300127 0
Condition category
Condition code
Public Health 300007 300007 0 0
Other public health
Metabolic and Endocrine 300030 300030 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
1) To compare the clinical effectiveness of three alternative pharmacy-based Diabetes Screening interventions:
a. Group A: screening based on AUSDRISK assessment tool alone with referral to a General Practitioner (GP) if AUSDRISK score greater than or equal to 12
b. Group B: AUSDRISK assessment tool + HbA1c Point of Care (POC) test in patients with AUSDRISK greater than or equal to 12 followed by the referral to a GP if HbA1c greater than or equal to 5.7% (39 mmol/mol) is detected
c. Group C: AUSDRISK assessment tool + capillary Blood Glucose Test Point of Care POC test in patients with AUSDRISKgreater than or equal to 12 followed by the referral to a GP if FBG greater than or equal to 5.5mmol/L or RBG greater than or equal to 7.0mmol/L is detected.
The primary outcome is the difference in proportions of newly diagnosed Type 2 diabetes mellitus cases between the two interventions and the comparator arm, based on the subsequent GP assessment and blood test results. The secondary outcomes are the difference in proportions of newly diagnosed cases of pre-diabetes, the proportion who take up the referral to the GP; and the proportion of people referred to the GP.
It is hypothesised that addition of either an HbA1c POC test or capillary Blood Glucose POC test to the AUSDRISK assessment alone is associated with a statistically significantly increase in the proportion of newly diagnosed Type 2 diabetes mellitus cases.
2) To assessing the technical efficiency of alternative groups of pharmacy-delivered screening for T2DM.

The AUSDRISK 1 assessment tool is used to identify risk of developing type 2 diabetes. It asks the individual to report on a list of risk factors for type 2 diabetes. Each risk factors has a score. Some risk factors carry a high score (previous high blood glucose, age over 65 and waist measurement exceeding threshold) compared with other risks that carry a low score (eating fruit and vegetables every day). The score is additive and total score can range from 0 to 36.
(1) Chen, L., D. J. Magliano, B. Balkau, S. Colagiuri, P. Z. Zimmet, A. M. Tonkin, P. Mitchell, P. J. Phillips and J. E. Shaw (2010). "AUSDRISK: an Australian Type 2 Diabetes Risk Assessment Tool based on demographic, lifestyle and simple anthropometric measures." Med J Aust 192(4): 197-202.
Intervention code [1] 295799 0
Early detection / Screening
Intervention code [2] 298788 0
Lifestyle
Comparator / control treatment
In this trial the comparative arm is Group A where participants will receive pharmacy screening based on AUSDRISK assessment tool alone with referral to a GP if AUSDRISK score greater than or equal to 12.
Control group
Active

Outcomes
Primary outcome [1] 299500 0
Proportion of newly detected Type 2 diabetes and Prediabetes diagnosed on the basis of an OGTT or a fasting plasma glucose test, according to the criteria of the Australian Diabetes Association
Timepoint [1] 299500 0
within 6 months post screening commencement
Secondary outcome [1] 327351 0
% diagnosed with pre-diabetes - patient survey and GP records


Timepoint [1] 327351 0
6 months post commencement of screening
Secondary outcome [2] 327454 0
Proportion who have been referred to the GP - pharmacy records
Timepoint [2] 327454 0
3 months post commencement of screening
Secondary outcome [3] 327455 0
Proportion who take up the referral to the GP - patient survey and, GP records
Timepoint [3] 327455 0
3 months post commencement of screening

Eligibility
Key inclusion criteria
Adults between 35 and 75 years old;
Living in the community (not a permanent resident of RACF ) or correction facility
Who do not have an established diagnosis of T2DM or pre-diabetes;or have not been screened in previous 12 months for T2DM/pre-diabetes using any of the tests included in the trial .
To be eligible to participate in this 6CPA Pharmacy Trial Program a community pharmacy must:
*be approved to dispense PBS medicines as part of the National Health Scheme defined in Section 90 of the National Health Act 1953 (Cth) (Section 90 pharmacy)
*have an area of the community pharmacy that is physically separated from the retail trading floor so that the privacy and confidentiality of the patient is protected
*appropriately store and dispose of reagents and consumables
*obtain written patient consent in accordance with the Australian Privacy Principles (APP 3, APP 5, APP 6, APP 11 and APP 12)
*be accredited by an approved Pharmacy Accreditation Program
*adhere to the appropriate standards, terms and conditions, guidelines and protocols when providing the service
*endeavours to include diabetes health check Continuing Professional Development (CPD) training in relevant pharmacists annual training plan as appropriate
*agree to provide the data required for the evaluation of this trial
Pharmacists who take part in the trial will be required to undertake a CPD accredited online training course to enable consistent delivery of the interventions across the trial. The online training course will be accredited through an appropriate independent organisation.


Minimum age
35 Years
Maximum age
75 Years
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Unable to give informed consent;
Women who are pregnant;
Based on patient self-report:
Has an established diagnosis of T2DM or pre-diabetes;
Has not been screened in previous 12 months for T2DM/pre-diabetes using any of the tests included in the trial
Terminal illness;
Has had a blood glucose test or OGTT for any other reasons associated with abnormal glucose homeostasis;

Subjects with severe hematologic diseases (e.g., thrombocytopenia, leukaemia);
Conditions not suitable for POC HbA1c testing
Subjects with shorter erythrocyte lifespan (e.g., chronic renal disease, thalassemia, other anaemia’s);
Subjects with haemoglobinopathy and red cell turnover disorders;
Iron deficiency anaemia.

Study design
Purpose of the study
Diagnosis
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
No
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software (i.e. computerised sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Clustered randomized controlled design - stratified sample of clusters by metropolitan/urban regional/rural,remote - random allocation to one of the 3 arms of the trial. All pharmacies in the cluster will implement the allocated service model for diabetes screening.
Phase
Not Applicable
Type of endpoint(s)
Efficacy
Statistical methods / analysis
The primary outcome is the probability of newly diagnosed T2DM from all referred participants according to the results of the screening tools. The probability is estimated by the proportion of newly diagnosed T2DM with respect to the ITT population (defined as all patients who met the RCT selection criteria).
Given the diverse demographic characteristics of participating pharmacies, we expect our sample to be similar in demographic characteristics to the Australian general population. Sample size calculations were based on a T2DM incidence of 4.6% distributed over the population age groups
The baseline PPV of AUSDRISK (the comparator), was estimated to be 10% and the ratio of PPVs in the intervention vs the comparator is conservatively assumed to be 30% based on the published PPV of the AUSDRISK + capillary blood glucose reported
The study needs to enrol 13,953 participants (4,651 in each group of the trial) in order to detect a 30% improvement on the ratio of PPVs of the screening methods (with AUSDRISK PPV as baseline), using a two-sided Cochran-Mantel-Haenszel (CMH) test conducted at the 5% significance level with 80% power, and making allowance for Type 2 diabetes (T2DM) incidence to range from 1.4% to 8.5% across the 4 age strata as shown in Table 7. Based on the distribution of clusters (pharmacies) according to the Australian metro/regional/rural population, an average of 85 participants per pharmacy was calculated.
Given the trial is a cluster trial, there is potential for observations for individuals within the same cluster to be correlated (i.e., the outcomes for individuals within clusters are likely to be more similar than those across clusters). Given the lack of evidence for the true value of Intraclass Correlation Coefficient (ICC), the estimated ICC of 0.001. was chosen to be consistent (i.e. within the range) with a cluster-randomised controlled trial on screening for T2DM and population mortality and a systematic review summarising patterns of ICC from primary care research. The values of the average cluster size (85 participants per pharmacy) and the assumed ICC (0.001) produced a design effect of 1.1 needed to account for pharmacy clustering effect (i.e., an inflation factor applied to the assumed variance around parameter estimates, which is necessary to allow for correlations among patients included within clusters).

In conclusion, a total of 15,360 participants are required in the study (5,120 in each group of the trial). The sample size is further inflated to allow for attrition of up to 50%, therefore the total sample to be recruited is 30,720 participants (10,240 in each group of the trial).
Since the alpha is spent on testing the null hypothesis associated with the primary objective that addition of either HbA1c Point of Care (POC) test or capillary blood glucose POC test to AUSDRISK assessment alone will be associated with a statistically significant increase in the proportion of new cases of T2DM in the intervention and the comparator arms
Statistical Analysis
We will adhere to ITT principles following CONSORT Statement guidelines. Baseline data will be secured prior to screening method allocation, missing values will be scrutinized to check for non-random distribution and analyses that utilize baseline data will be executed twice: once using observed data, and once using multiple imputation method. The Cochran-Mantel-Haenszel (CMH) test will be used to compare the differences in proportions of true T2DM detected between the screening methods. The CMH test takes account of the stratified randomisation and allows for variation between the strata in the underlying rates. The common odds ratio and its 95% confidence interval will also be reported as well as the results of the Breslow-Day test for homogeneity of the odds ratios across the strata. If there is significant heterogeneity in the odds ratios, the screening groups will also be compared, using Chi-squared tests, in separate subset analyses. In further supportive analyses, generalized linear mixed models (GLMMs) will be used to compare the probability of newly diagnosed T2DM after adjusting for clustering effect of pharmacy, baseline measurements and to explore possible interactions between baseline factors and screening methods.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
ACT,NSW,NT,QLD,SA,TAS,WA,VIC

Funding & Sponsors
Funding source category [1] 294438 0
Government body
Name [1] 294438 0
Commonwealth of Australia as represented by the Department of Health
Address [1] 294438 0
MDP 901,
GPO Box 9848,
Canberra
ACT 2601
Country [1] 294438 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
The Pharmacy Guild of Australia
Address
Level 2, 15 National Circuit, Barton, ACT 2600 Australia
PO Box 310, Fyshwick, ACT 2609 Australia
Country
Australia
Secondary sponsor category [1] 293291 0
University
Name [1] 293291 0
University of Sydney
Address [1] 293291 0
THE UNIVERSITY OF SYDNEY
Camperdown
NSW 2006
Country [1] 293291 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 295868 0
University of Sydney Human Ethics Committee
Ethics committee address [1] 295868 0
THE UNIVERSITY OF SYDNEY
Level 2 Margaret Telfer Building (K07)
The University of Sydney
NSW 2006

Ethics committee country [1] 295868 0
Australia
Date submitted for ethics approval [1] 295868 0
06/07/2015
Approval date [1] 295868 0
30/08/2016
Ethics approval number [1] 295868 0
2016/637

Summary
Brief summary
The objective of the Pharmacy Diabetes Screening trial funded under the Sixth Community Pharmacy Agreement (6CPA) Pharmacy Trial Program (PTP), and developed in partnership with the University of Sydney and Deakin University is to assess the comparative effectiveness and cost-effectiveness of alternative pharmacy-delivered models of opportunistic assessment for diabetes in an asymptomatic, previously undiagnosed population.
The three groups to be compared include:
Group A: screening based on Australian Diabetes Risk Assessment Tool (AUSDRISK) alone with referral to a GP if AUSDRISK greater than or equal to 12
Group B: AUSDRISK assessment tool + HbA1c point-of-care (POC) test in patients with AUSDRISK greater than or equal to 12 followed by the referral to a GP if HbA1c greater than or equal to 5.7% (39 mmol/mol is detected
Group C: AUSDRISK assessment tool + small capillary blood glucose test (scBGT) in patients with AUSDRISK greater than or equal to 12 followed by the referral to a GP if fasting blood glucose (FBG) greater than or equal to 5.5mmol/L or random blood glucose (RBG)greater than or equal to 7.0mmol/L is detected.
The primary outcome is the difference in proportions of newly diagnosed T2DM cases between the two interventions and the comparator arm to be identified by the subsequent GP assessment and blood tests results. The secondary outcomes to be assessed include: a) proportion of new diagnosed cases of pre-diabetes; b) proportion who take up the referral to the GP; and c) proportion of people referred to the GP.
It is anticipated that this project will take approximately 20 months during which there will be approximately seven months of service provision.
The primary economic objective of the study is to assess the technical efficiency of alternative models of pharmacy-delivered screening for T2DM. The broader objective of determining the value-for-money of pharmacy-delivered screening versus current practice (which does not involve pharmacy-delivered screening/referral), as would, for example, be required in a submission to MSAC requesting subsidy of pharmacy-delivered screening, is not addressed by the trial protocol. There is nonetheless an important value-for-money element to this trial. In the context of opportunistic screening to improve detection of T2DM, the population that visits GPs is different to the population that visits community pharmacies in one important aspect – people can just walk into pharmacies without an appointment, whereas this would be unusual for GPs. This difference in target populations potentially adds an allocative efficiency aspect to the ‘how to screen’ question.
Trial website
none
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 68734 0
Prof Ines Krass
Address 68734 0
Faculty of Pharmacy
University of Sydney
Camperdown
NSW 2006
Country 68734 0
Australia
Phone 68734 0
+61293513507
Fax 68734 0
+6193514391
Email 68734 0
ines.krass@sydney.edu.au
Contact person for public queries
Name 68735 0
Ms Erica Vowles
Address 68735 0
The Pharmacy Guild of Australia
National Secretariat
The Pharmacy Guild of Australia
Level 2, 15 National Circuit, Barton ACT 2600 Australia
PO Box 310, Fyshwick ACT 2609 Australia

Country 68735 0
Australia
Phone 68735 0
+ 61 2 6270 1605
Fax 68735 0
+ 61 2 6270 1800
Email 68735 0
Erica.Vowles@guild.org.au
Contact person for scientific queries
Name 68736 0
Prof Ines Krass
Address 68736 0
Faculty of Pharmacy
University of Sydney
Camperdown
NSW 2006
Country 68736 0
Australia
Phone 68736 0
+61-2-93513507
Fax 68736 0
+61-2-93514391
Email 68736 0
ines.krass@sydney.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No/undecided IPD sharing reason/comment
What supporting documents are/will be available?
Summary results
Have study results been published in a peer-reviewed journal?
No
Other publications
Have study results been made publicly available in another format?
No
Results – basic reporting
Results – plain English summary