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...
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Journal article |
| Language: | English |
| Published: |
BMJ Publishing Group
2021
|
| _version_ | 1797068235632279552 |
|---|---|
| author | Bidulka, P O'Neill, S Basu, A Wilkinson, S Silverwood, RJ Charlton, P Briggs, A Adler, AI Khunti, K Tomlinson, LA Smeeth, L Douglas, IJ Grieve, R |
| author_facet | Bidulka, P O'Neill, S Basu, A Wilkinson, S Silverwood, RJ Charlton, P Briggs, A Adler, AI Khunti, K Tomlinson, LA Smeeth, L Douglas, IJ Grieve, R |
| author_sort | Bidulka, P |
| collection | OXFORD |
| 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.
|
| first_indexed | 2024-03-06T22:07:48Z |
| format | Journal article |
| id | oxford-uuid:50c05cab-c25d-4c38-9464-e7445bf23f05 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T22:07:48Z |
| publishDate | 2021 |
| publisher | BMJ Publishing Group |
| record_format | dspace |
| spelling | oxford-uuid:50c05cab-c25d-4c38-9464-e7445bf23f052022-03-26T16:15:31ZProtocol for an observational cohort study investigating personalised medicine for intensification of treatment in people with type 2 diabetes mellitus: the PERMIT studyJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:50c05cab-c25d-4c38-9464-e7445bf23f05EnglishSymplectic ElementsBMJ Publishing Group2021Bidulka, PO'Neill, SBasu, AWilkinson, SSilverwood, RJCharlton, PBriggs, AAdler, AIKhunti, KTomlinson, LASmeeth, LDouglas, IJGrieve, RIntroduction 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. |
| spellingShingle | Bidulka, P O'Neill, S Basu, A Wilkinson, S Silverwood, RJ Charlton, P Briggs, A Adler, AI Khunti, K Tomlinson, LA Smeeth, L Douglas, IJ Grieve, R Protocol for an observational cohort study investigating personalised medicine for intensification of treatment in people with type 2 diabetes mellitus: the PERMIT study |
| 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 |
| work_keys_str_mv | AT bidulkap protocolforanobservationalcohortstudyinvestigatingpersonalisedmedicineforintensificationoftreatmentinpeoplewithtype2diabetesmellitusthepermitstudy AT oneills protocolforanobservationalcohortstudyinvestigatingpersonalisedmedicineforintensificationoftreatmentinpeoplewithtype2diabetesmellitusthepermitstudy AT basua protocolforanobservationalcohortstudyinvestigatingpersonalisedmedicineforintensificationoftreatmentinpeoplewithtype2diabetesmellitusthepermitstudy AT wilkinsons protocolforanobservationalcohortstudyinvestigatingpersonalisedmedicineforintensificationoftreatmentinpeoplewithtype2diabetesmellitusthepermitstudy AT silverwoodrj protocolforanobservationalcohortstudyinvestigatingpersonalisedmedicineforintensificationoftreatmentinpeoplewithtype2diabetesmellitusthepermitstudy AT charltonp protocolforanobservationalcohortstudyinvestigatingpersonalisedmedicineforintensificationoftreatmentinpeoplewithtype2diabetesmellitusthepermitstudy AT briggsa protocolforanobservationalcohortstudyinvestigatingpersonalisedmedicineforintensificationoftreatmentinpeoplewithtype2diabetesmellitusthepermitstudy AT adlerai protocolforanobservationalcohortstudyinvestigatingpersonalisedmedicineforintensificationoftreatmentinpeoplewithtype2diabetesmellitusthepermitstudy AT khuntik protocolforanobservationalcohortstudyinvestigatingpersonalisedmedicineforintensificationoftreatmentinpeoplewithtype2diabetesmellitusthepermitstudy AT tomlinsonla protocolforanobservationalcohortstudyinvestigatingpersonalisedmedicineforintensificationoftreatmentinpeoplewithtype2diabetesmellitusthepermitstudy AT smeethl protocolforanobservationalcohortstudyinvestigatingpersonalisedmedicineforintensificationoftreatmentinpeoplewithtype2diabetesmellitusthepermitstudy AT douglasij protocolforanobservationalcohortstudyinvestigatingpersonalisedmedicineforintensificationoftreatmentinpeoplewithtype2diabetesmellitusthepermitstudy AT griever protocolforanobservationalcohortstudyinvestigatingpersonalisedmedicineforintensificationoftreatmentinpeoplewithtype2diabetesmellitusthepermitstudy |