Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 Mar 11;8(1):62.
doi: 10.1186/s40814-022-01016-0.

Evaluating Diuretics in Normal Care (EVIDENCE): a feasibility report of a pilot cluster randomised trial of prescribing policy in primary care to compare the effectiveness of thiazide-type diuretics in hypertension

Angela Flynn  1 , Amy Rogers  2 , Lewis McConnachie  2 , Rebecca Barr  2 , Robert W V Flynn  2 , Isla S Mackenzie  2 , Thomas M MacDonald  2 , Alexander S F Doney  2
Affiliations

Evaluating Diuretics in Normal Care (EVIDENCE): a feasibility report of a pilot cluster randomised trial of prescribing policy in primary care to compare the effectiveness of thiazide-type diuretics in hypertension

Angela Flynn et al. Pilot Feasibility Stud. .

Abstract

Background: Obtaining evidence on comparative effectiveness and safety of widely prescribed drugs in a timely and cost-effective way is a major challenge for healthcare systems. Here, we describe the feasibility of the Evaluating Diuretics in Normal Care (EVIDENCE) study that compares a thiazide and thiazide-like diuretics for hypertension as an exemplar of a more general framework for efficient generation of such evidence. In 2011, the UK NICE hypertension guideline included a recommendation that thiazide-like diuretics (such as indapamide) be used in preference to thiazide diuretics (such as bendroflumethiazide) for hypertension. There is sparse evidence backing this recommendation, and bendroflumethiazide remains widely used in the UK.

Methods: Patients prescribed indapamide or bendroflumethiazide regularly for hypertension were identified in participating general practices. Allocation of a prescribing policy favouring one of these drugs was then randomly applied to the practice and, where required to comply with the policy, repeat prescriptions switched by pharmacy staff. Patients were informed of the potential switch by letter and given the opportunity to opt out. Practice adherence to the randomised policy was assessed by measuring the amount of policy drug prescribed as a proportion of total combined indapamide and bendroflumethiazide. Routinely collected hospitalisation and death data in the NHS will be used to compare cardiovascular event rates between the two policies.

Results: This pilot recruited 30 primary care practices in five Scottish National Health Service (NHS) Boards. Fifteen practices were randomised to indapamide (2682 patients) and 15 to bendroflumethiazide (3437 patients), a study population of 6119 patients. Prior to randomisation, bendroflumethiazide was prescribed to 78% of patients prescribed either of these drugs. Only 1.6% of patients opted out of the proposed medication switch.

Conclusion: The pilot and subsequent recruitment confirms the methodology is scalable within NHS Scotland for a fully powered larger study; currently, 102 GP practices (> 12,700 patients) are participating in this study. It has the potential to efficiently produce externally valid comparative effectiveness data with minimal disruption to practice staff or patients. Streamlining this pragmatic trial approach has demonstrated the feasibility of a random prescribing policy design framework that can be adapted to other therapeutic areas.

Trial registration: ISRCTN Registry, ISRCTN46635087 . Registered on 11 August 2017.

Keywords: Comparative effectiveness; Drug prescriptions; Hypertension; Pilot; Prescribing policy; Primary care.

PubMed Disclaimer

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Consort style flow chart showing the results of practice recruitment to pilot study and resulting study population including patient opt-out percentage
Fig. 2
Fig. 2
A plot showing practice adherence following prescription switches over time to the randomised policy for practices randomised to bendroflumethiazide and indapamide
See this image and copyright information in PMC

Similar articles

See all similar articles

References

    1. Gagne JJ, Choudhry NK. How many “me-too” drugs is too many? JAMA. 2011;305(7):711–712. doi: 10.1001/jama.2011.152. - DOI - PubMed
    1. Cipriani A, Ioannidis JPA, Rothwell PM, Glasziou P, Li T, Hernandez AF, et al. Generating comparative evidence on new drugs and devices after approval. Lancet. 2020;395(10228):998–1010. doi: 10.1016/S0140-6736(19)33177-0. - DOI - PubMed
    1. Naci H, Salcher-Konrad M, Kesselheim AS, Wieseler B, Rochaix L, Redberg RF, et al. Generating comparative evidence on new drugs and devices before approval. Lancet. 2020;395(10228):986–997. doi: 10.1016/S0140-6736(19)33178-2. - DOI - PubMed
    1. Guthrie B, Boyd CM. Clinical guidelines in the context of aging and multimorbidity. Public Policy Aging Rep. 2018;28(4):143–149. doi: 10.1093/ppar/pry038. - DOI
    1. Saunders C, Byrne CD, Guthrie B, Lindsay RS, McKnight JA, Philip S, et al. External validity of randomized controlled trials of glycaemic control and vascular disease: how representative are participants? Diabetic Med. 2013;30(3):300–308. doi: 10.1111/dme.12047. - DOI - PubMed

LinkOut - more resources