Evaluating Diuretics in Normal Care (EVIDENCE): protocol of a cluster randomised controlled equivalence trial of prescribing policy to compare the effectiveness of thiazide-type diuretics in hypertension
Abstract Introduction Healthcare systems must use treatments that are effective and safe. Regulators licensed many currently used older medications before introducing the stringent evidential requirements imposed on modern treatments. Also, there has been little encouragement to carry out within-cla...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2021-11-01
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| Series: | Trials |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13063-021-05782-9 |
| _version_ | 1798034810281656320 |
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| author | Amy Rogers Angela Flynn Isla S. Mackenzie Lewis McConnachie Rebecca Barr Robert W. V. Flynn Steve Morant Thomas M. MacDonald Alexander Doney |
| author_facet | Amy Rogers Angela Flynn Isla S. Mackenzie Lewis McConnachie Rebecca Barr Robert W. V. Flynn Steve Morant Thomas M. MacDonald Alexander Doney |
| author_sort | Amy Rogers |
| collection | DOAJ |
| description | Abstract Introduction Healthcare systems must use treatments that are effective and safe. Regulators licensed many currently used older medications before introducing the stringent evidential requirements imposed on modern treatments. Also, there has been little encouragement to carry out within-class, head-to-head comparisons of licensed medicines. For commonly prescribed drugs, even small differences in effectiveness or safety could have significant public health implications. However, conventional clinical trials that randomise individual subjects are costly and unwieldy. Such trials are also often criticised as having low external validity. We describe an approach to rapidly generate externally valid evidence of comparative safety and effectiveness using the example of two widely used diuretics for the management of hypertension. Methods and analysis The EVIDENCE (Evaluating Diuretics in Normal Care) study has a prospective, cluster-randomised, open-label, blinded end-point design. By randomising prescribing policy in primary care practices, the study compares the safety and effectiveness of commonly used diuretics in treating hypertension. Participating practices are randomised 1:1 to a policy of prescribing either indapamide or bendroflumethiazide when clinically indicated. Suitable patients who are not already taking the policy diuretic are switched accordingly. All patients taking the study medications are written to explaining the rationale for changing the prescribing policy and notifying them they can opt-out of any switch. The prescribing policies’ effectiveness and safety will be compared using rates of major adverse cardiovascular events (hospitalisation with myocardial infarction, heart failure or stroke or cardiovascular death), routinely collected in national healthcare administrative datasets. The study will seek to recruit 250 practices to provide a study population of approximately 50,000 individuals with a mean follow-up time of two years. A primary intention-to-treat time-to-event analysis will be used to estimate the relative effect of the two policies. Ethics and dissemination EVIDENCE has been approved by the East of Scotland Research Ethics Service (17/ES/0016, current approved protocol version 5, 26 August 2021). The results will be disseminated widely in peer reviewed journals, guideline committees, National Health Service (NHS) organisations and patient groups. Trial registration ISRCTN 46635087 . Registered on 11 August 2017 (pre-recruitment). |
| first_indexed | 2024-04-11T20:48:42Z |
| format | Article |
| id | doaj.art-db35f143f525469a8bbe701a1404d31e |
| institution | Directory Open Access Journal |
| issn | 1745-6215 |
| language | English |
| last_indexed | 2024-04-11T20:48:42Z |
| publishDate | 2021-11-01 |
| publisher | BMC |
| record_format | Article |
| series | Trials |
| spelling | doaj.art-db35f143f525469a8bbe701a1404d31e2022-12-22T04:03:55ZengBMCTrials1745-62152021-11-012211910.1186/s13063-021-05782-9Evaluating Diuretics in Normal Care (EVIDENCE): protocol of a cluster randomised controlled equivalence trial of prescribing policy to compare the effectiveness of thiazide-type diuretics in hypertensionAmy Rogers0Angela Flynn1Isla S. Mackenzie2Lewis McConnachie3Rebecca Barr4Robert W. V. Flynn5Steve Morant6Thomas M. MacDonald7Alexander Doney8MEMO Research, University of Dundee, Ninewells Hospital and Medical SchoolMEMO Research, University of Dundee, Ninewells Hospital and Medical SchoolMEMO Research, University of Dundee, Ninewells Hospital and Medical SchoolMEMO Research, University of Dundee, Ninewells Hospital and Medical SchoolMEMO Research, University of Dundee, Ninewells Hospital and Medical SchoolMEMO Research, University of Dundee, Ninewells Hospital and Medical SchoolMEMO Research, University of Dundee, Ninewells Hospital and Medical SchoolMEMO Research, University of Dundee, Ninewells Hospital and Medical SchoolMEMO Research, University of Dundee, Ninewells Hospital and Medical SchoolAbstract Introduction Healthcare systems must use treatments that are effective and safe. Regulators licensed many currently used older medications before introducing the stringent evidential requirements imposed on modern treatments. Also, there has been little encouragement to carry out within-class, head-to-head comparisons of licensed medicines. For commonly prescribed drugs, even small differences in effectiveness or safety could have significant public health implications. However, conventional clinical trials that randomise individual subjects are costly and unwieldy. Such trials are also often criticised as having low external validity. We describe an approach to rapidly generate externally valid evidence of comparative safety and effectiveness using the example of two widely used diuretics for the management of hypertension. Methods and analysis The EVIDENCE (Evaluating Diuretics in Normal Care) study has a prospective, cluster-randomised, open-label, blinded end-point design. By randomising prescribing policy in primary care practices, the study compares the safety and effectiveness of commonly used diuretics in treating hypertension. Participating practices are randomised 1:1 to a policy of prescribing either indapamide or bendroflumethiazide when clinically indicated. Suitable patients who are not already taking the policy diuretic are switched accordingly. All patients taking the study medications are written to explaining the rationale for changing the prescribing policy and notifying them they can opt-out of any switch. The prescribing policies’ effectiveness and safety will be compared using rates of major adverse cardiovascular events (hospitalisation with myocardial infarction, heart failure or stroke or cardiovascular death), routinely collected in national healthcare administrative datasets. The study will seek to recruit 250 practices to provide a study population of approximately 50,000 individuals with a mean follow-up time of two years. A primary intention-to-treat time-to-event analysis will be used to estimate the relative effect of the two policies. Ethics and dissemination EVIDENCE has been approved by the East of Scotland Research Ethics Service (17/ES/0016, current approved protocol version 5, 26 August 2021). The results will be disseminated widely in peer reviewed journals, guideline committees, National Health Service (NHS) organisations and patient groups. Trial registration ISRCTN 46635087 . Registered on 11 August 2017 (pre-recruitment).https://doi.org/10.1186/s13063-021-05782-9Medical record linkageComparative effectiveness researchDrug prescriptionsPrimary health careHypertension |
| spellingShingle | Amy Rogers Angela Flynn Isla S. Mackenzie Lewis McConnachie Rebecca Barr Robert W. V. Flynn Steve Morant Thomas M. MacDonald Alexander Doney Evaluating Diuretics in Normal Care (EVIDENCE): protocol of a cluster randomised controlled equivalence trial of prescribing policy to compare the effectiveness of thiazide-type diuretics in hypertension Trials Medical record linkage Comparative effectiveness research Drug prescriptions Primary health care Hypertension |
| title | Evaluating Diuretics in Normal Care (EVIDENCE): protocol of a cluster randomised controlled equivalence trial of prescribing policy to compare the effectiveness of thiazide-type diuretics in hypertension |
| title_full | Evaluating Diuretics in Normal Care (EVIDENCE): protocol of a cluster randomised controlled equivalence trial of prescribing policy to compare the effectiveness of thiazide-type diuretics in hypertension |
| title_fullStr | Evaluating Diuretics in Normal Care (EVIDENCE): protocol of a cluster randomised controlled equivalence trial of prescribing policy to compare the effectiveness of thiazide-type diuretics in hypertension |
| title_full_unstemmed | Evaluating Diuretics in Normal Care (EVIDENCE): protocol of a cluster randomised controlled equivalence trial of prescribing policy to compare the effectiveness of thiazide-type diuretics in hypertension |
| title_short | Evaluating Diuretics in Normal Care (EVIDENCE): protocol of a cluster randomised controlled equivalence trial of prescribing policy to compare the effectiveness of thiazide-type diuretics in hypertension |
| title_sort | evaluating diuretics in normal care evidence protocol of a cluster randomised controlled equivalence trial of prescribing policy to compare the effectiveness of thiazide type diuretics in hypertension |
| topic | Medical record linkage Comparative effectiveness research Drug prescriptions Primary health care Hypertension |
| url | https://doi.org/10.1186/s13063-021-05782-9 |
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