Protocol for an observational cohort study investigating personalised medicine for intensification of treatment in people with type 2 diabetes mellitus: the PERMIT study
Introduction For people with type 2 diabetes mellitus (T2DM) who require an antidiabetic drug as an add-on to metformin, there is controversy about whether newer drug classes such as dipeptidyl peptidase-4 inhibitors (DPP4i) or sodium-glucose co-transporter-2 inhibitors (SGLT2i) reduce the risk of l...
Saved in:
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMJ Publishing Group
2021-09-01
|
| Series: | BMJ Open |
| Online Access: | https://bmjopen.bmj.com/content/11/9/e046912.full |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850179608853348352 |
|---|---|
| author | Kamlesh Khunti Samantha Wilkinson Liam Smeeth Laurie A Tomlinson Amanda I Adler Ian J Douglas Andrew Briggs Richard Grieve Stephen O’neill Richard J Silverwood Paul Charlton Patrick Bidulka Anirban Basu |
| author_facet | Kamlesh Khunti Samantha Wilkinson Liam Smeeth Laurie A Tomlinson Amanda I Adler Ian J Douglas Andrew Briggs Richard Grieve Stephen O’neill Richard J Silverwood Paul Charlton Patrick Bidulka Anirban Basu |
| author_sort | Kamlesh Khunti |
| collection | DOAJ |
| description | Introduction For people with type 2 diabetes mellitus (T2DM) who require an antidiabetic drug as an add-on to metformin, there is controversy about whether newer drug classes such as dipeptidyl peptidase-4 inhibitors (DPP4i) or sodium-glucose co-transporter-2 inhibitors (SGLT2i) reduce the risk of long-term complications compared with sulfonylureas (SU). There is widespread variation across National Health Service Clinical Commissioning Groups (CCGs) in drug choice for second-line treatment in part because National Institute for Health and Care Excellence guidelines do not specify a single preferred drug class, either overall or within specific patient subgroups. This study will evaluate the relative effectiveness of the three most common second-line treatments in the UK (SU, DPP4i and SGLT2i as add-ons to metformin) and help target treatments according to individual risk profiles.Methods and analysis The study includes people with T2DM prescribed one of the second-line treatments-of-interest between 2014 and 2020 within the UK Clinical Practice Research Datalink linked with Hospital Episode Statistics and Office of National Statistics. We will use an instrumental variable (IV) method to estimate short-term and long-term relative effectiveness of second-line treatments according to individuals’ risk profiles. This method minimises bias from unmeasured confounders by exploiting the natural variation in second-line prescribing across CCGs as an IV for the choice of prescribed treatment. The primary outcome to assess short-term effectiveness will be change in haemoglobin A1c (%) 12 months after treatment initiation. Outcome measures to assess longer-term effectiveness (maximum ~6 years) will include microvascular and macrovascular complications, all-cause mortality and hospital admissions during follow-up.Ethics and dissemination This study was approved by the Independent Scientific Advisory Committee (20-064) and the London School of Hygiene & Tropical Medicine Research Ethics Committee (21395). Results, codelists and other analysis code will be made available to patients, clinicians, policy-makers and researchers. |
| format | Article |
| id | doaj-art-33fdba588b1043e1a5ec01b6dca7066c |
| institution | OA Journals |
| issn | 2044-6055 |
| language | English |
| publishDate | 2021-09-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | BMJ Open |
| spelling | doaj-art-33fdba588b1043e1a5ec01b6dca7066c2025-08-20T02:18:27ZengBMJ Publishing GroupBMJ Open2044-60552021-09-0111910.1136/bmjopen-2020-046912Protocol for an observational cohort study investigating personalised medicine for intensification of treatment in people with type 2 diabetes mellitus: the PERMIT studyKamlesh Khunti0Samantha Wilkinson1Liam Smeeth2Laurie A Tomlinson3Amanda I Adler4Ian J Douglas5Andrew Briggs6Richard Grieve7Stephen O’neill8Richard J Silverwood9Paul Charlton10Patrick Bidulka11Anirban Basu12Leicester Real World Evidence Unit, Diabetes Research Centre, University of Leicester, Leicester, UKPersonalized Healthcare Data Science, Roche Products Limited, Welwyn Garden City, UKprofessor1 London School of Hygiene & Tropical Medicine, London, UK2 Diabetes Trials Unit, Radcliffe Department of Medicine, University of Oxford, Oxford, UKprofessorLindsay chair in health policy & economic evaluationDepartment of Health Services Research and Policy, London School of Hygiene and Tropical Medicine, London, UKDepartment of Health Services Research and Policy, London School of Hygiene and Tropical Medicine, London, UKassistant professorPatient Research Champion Team, National Institute for Health Research, Twickenham, UK1 London School of Hygiene & Tropical Medicine, London, UKPediatrics, PGIMER, Chandigarh, IndiaIntroduction For people with type 2 diabetes mellitus (T2DM) who require an antidiabetic drug as an add-on to metformin, there is controversy about whether newer drug classes such as dipeptidyl peptidase-4 inhibitors (DPP4i) or sodium-glucose co-transporter-2 inhibitors (SGLT2i) reduce the risk of long-term complications compared with sulfonylureas (SU). There is widespread variation across National Health Service Clinical Commissioning Groups (CCGs) in drug choice for second-line treatment in part because National Institute for Health and Care Excellence guidelines do not specify a single preferred drug class, either overall or within specific patient subgroups. This study will evaluate the relative effectiveness of the three most common second-line treatments in the UK (SU, DPP4i and SGLT2i as add-ons to metformin) and help target treatments according to individual risk profiles.Methods and analysis The study includes people with T2DM prescribed one of the second-line treatments-of-interest between 2014 and 2020 within the UK Clinical Practice Research Datalink linked with Hospital Episode Statistics and Office of National Statistics. We will use an instrumental variable (IV) method to estimate short-term and long-term relative effectiveness of second-line treatments according to individuals’ risk profiles. This method minimises bias from unmeasured confounders by exploiting the natural variation in second-line prescribing across CCGs as an IV for the choice of prescribed treatment. The primary outcome to assess short-term effectiveness will be change in haemoglobin A1c (%) 12 months after treatment initiation. Outcome measures to assess longer-term effectiveness (maximum ~6 years) will include microvascular and macrovascular complications, all-cause mortality and hospital admissions during follow-up.Ethics and dissemination This study was approved by the Independent Scientific Advisory Committee (20-064) and the London School of Hygiene & Tropical Medicine Research Ethics Committee (21395). Results, codelists and other analysis code will be made available to patients, clinicians, policy-makers and researchers.https://bmjopen.bmj.com/content/11/9/e046912.full |
| spellingShingle | Kamlesh Khunti Samantha Wilkinson Liam Smeeth Laurie A Tomlinson Amanda I Adler Ian J Douglas Andrew Briggs Richard Grieve Stephen O’neill Richard J Silverwood Paul Charlton Patrick Bidulka Anirban Basu Protocol for an observational cohort study investigating personalised medicine for intensification of treatment in people with type 2 diabetes mellitus: the PERMIT study BMJ Open |
| title | Protocol for an observational cohort study investigating personalised medicine for intensification of treatment in people with type 2 diabetes mellitus: the PERMIT study |
| title_full | Protocol for an observational cohort study investigating personalised medicine for intensification of treatment in people with type 2 diabetes mellitus: the PERMIT study |
| title_fullStr | Protocol for an observational cohort study investigating personalised medicine for intensification of treatment in people with type 2 diabetes mellitus: the PERMIT study |
| title_full_unstemmed | Protocol for an observational cohort study investigating personalised medicine for intensification of treatment in people with type 2 diabetes mellitus: the PERMIT study |
| title_short | Protocol for an observational cohort study investigating personalised medicine for intensification of treatment in people with type 2 diabetes mellitus: the PERMIT study |
| title_sort | protocol for an observational cohort study investigating personalised medicine for intensification of treatment in people with type 2 diabetes mellitus the permit study |
| url | https://bmjopen.bmj.com/content/11/9/e046912.full |
| work_keys_str_mv | AT kamleshkhunti protocolforanobservationalcohortstudyinvestigatingpersonalisedmedicineforintensificationoftreatmentinpeoplewithtype2diabetesmellitusthepermitstudy AT samanthawilkinson protocolforanobservationalcohortstudyinvestigatingpersonalisedmedicineforintensificationoftreatmentinpeoplewithtype2diabetesmellitusthepermitstudy AT liamsmeeth protocolforanobservationalcohortstudyinvestigatingpersonalisedmedicineforintensificationoftreatmentinpeoplewithtype2diabetesmellitusthepermitstudy AT laurieatomlinson protocolforanobservationalcohortstudyinvestigatingpersonalisedmedicineforintensificationoftreatmentinpeoplewithtype2diabetesmellitusthepermitstudy AT amandaiadler protocolforanobservationalcohortstudyinvestigatingpersonalisedmedicineforintensificationoftreatmentinpeoplewithtype2diabetesmellitusthepermitstudy AT ianjdouglas protocolforanobservationalcohortstudyinvestigatingpersonalisedmedicineforintensificationoftreatmentinpeoplewithtype2diabetesmellitusthepermitstudy AT andrewbriggs protocolforanobservationalcohortstudyinvestigatingpersonalisedmedicineforintensificationoftreatmentinpeoplewithtype2diabetesmellitusthepermitstudy AT richardgrieve protocolforanobservationalcohortstudyinvestigatingpersonalisedmedicineforintensificationoftreatmentinpeoplewithtype2diabetesmellitusthepermitstudy AT stephenoneill protocolforanobservationalcohortstudyinvestigatingpersonalisedmedicineforintensificationoftreatmentinpeoplewithtype2diabetesmellitusthepermitstudy AT richardjsilverwood protocolforanobservationalcohortstudyinvestigatingpersonalisedmedicineforintensificationoftreatmentinpeoplewithtype2diabetesmellitusthepermitstudy AT paulcharlton protocolforanobservationalcohortstudyinvestigatingpersonalisedmedicineforintensificationoftreatmentinpeoplewithtype2diabetesmellitusthepermitstudy AT patrickbidulka protocolforanobservationalcohortstudyinvestigatingpersonalisedmedicineforintensificationoftreatmentinpeoplewithtype2diabetesmellitusthepermitstudy AT anirbanbasu protocolforanobservationalcohortstudyinvestigatingpersonalisedmedicineforintensificationoftreatmentinpeoplewithtype2diabetesmellitusthepermitstudy |