eprintid: 10135831
rev_number: 12
eprint_status: archive
userid: 608
dir: disk0/10/13/58/31
datestamp: 2021-10-07 12:10:00
lastmod: 2021-10-07 12:10:00
status_changed: 2021-10-07 12:10:00
type: article
metadata_visibility: show
creators_name: Bidulka, P
creators_name: O'Neill, S
creators_name: Basu, A
creators_name: Wilkinson, S
creators_name: Silverwood, RJ
creators_name: Charlton, P
creators_name: Briggs, A
creators_name: Adler, AI
creators_name: Khunti, K
creators_name: Tomlinson, LA
creators_name: Smeeth, L
creators_name: Douglas, IJ
creators_name: Grieve, R
title: Protocol for an observational cohort study investigating personalised medicine for intensification of treatment in people with type 2 diabetes mellitus: the PERMIT study
ispublished: pub
divisions: UCL
divisions: B16
divisions: B14
divisions: J81
keywords: diabetes & endocrinology, epidemiology, statistics & research methods
note: This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license.
abstract: 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.
date: 2021-09-27
date_type: published
official_url: http://dx.doi.org/10.1136/bmjopen-2020-046912
oa_status: green
full_text_type: pub
language: eng
primo: open
primo_central: open_green
verified: verified_manual
elements_id: 1890985
doi: 10.1136/bmjopen-2020-046912
pii: bmjopen-2020-046912
lyricists_name: Silverwood, Richard
lyricists_id: RSILV59
actors_name: Kalinowski, Damian
actors_id: DKALI47
actors_role: owner
full_text_status: public
publication: BMJ Open
volume: 11
number: 9
article_number: e046912
event_location: England
issn: 2044-6055
citation:        Bidulka, P;    O'Neill, S;    Basu, A;    Wilkinson, S;    Silverwood, RJ;    Charlton, P;    Briggs, A;                         ... Grieve, R; + view all <#>        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;   - view fewer <#>    (2021)    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 , 11  (9)    , Article e046912.  10.1136/bmjopen-2020-046912 <https://doi.org/10.1136/bmjopen-2020-046912>.       Green open access   
 
document_url: https://discovery.ucl.ac.uk/id/eprint/10135831/1/Silverwood_Protocol%20for%20an%20observational%20cohort%20study%20investigating%20personalised%20medicine%20for%20intensification%20of%20treatment%20in%20people%20with%20type%202%20diabetes%20mellitus-%20the%20PERMIT%20study_VoR.pdf