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20/109 Shorter vs longer fixed-course antibiotic treatments




The aim of the HTA Programme is to ensure that high quality research information on the effectiveness, costs and broader impact of health technology is produced in the most efficient way for those who use, manage, provide care in or develop policy for the NHS. Topics for research are identified and prioritised to meet the needs of the NHS. Health technology assessment forms a substantial portfolio of work within the National Institute for Health Research and each year about fifty new studies are commissioned to help answer questions of direct importance to the NHS. The studies include both primary research and evidence synthesis.
This is a brief of broader scope from which the programme is interested in potentially funding more than one proposal.
We are interested in proposals for definitive primary research to determine the effectiveness of shorter fixed courses of antibiotics compared to longer (standard) fixed courses of antibiotics, where there is potential to change prescribing practice in the UK. Applicants should define the specific condition(s) for which shorter antibiotic treatments will be evaluated and demonstrate how the existing evidence base justifies their choice, in particular with reference to:
  • lack of evidence for currently prescribed durations for the given conditions (treatment being based on custom and/or highly variable in practice);
  • the burden of potential over-prescription;
  • evidence that antibiotics are justified at all; and
  • sufficient frequency of clinical events to warrant research.

Applicants should also clearly define and justify their choice of patient group, study design and outcome measures and delineate a detailed pathway to impact, as well as explaining how the research will fit into the remit of the HTA programme.

Applications based in primary and/or secondary care are welcome. If the treatment is administered out of hospital, applicants should explain whether adherence will be recorded, and if so how this will be measured.


Large numbers of antibiotics are prescribed each year for suspected or confirmed infections in both hospital and primary care settings. The duration of antibiotic treatment is frequently determined not by evidence from research but by custom, much of it shaped by deeply ingrained warnings against stopping too soon.  However, there has been growing realisation that unnecessarily long courses of antibiotics may entail serious costs and risks for individual patients, as well as the entire healthcare system.
In the individual patient, every dose of antibiotics alters the natural microbiome of the digestive system, potentially selecting for Clostridium difficile, which is a common cause of diarrhoea and may be life threatening in vulnerable people. Other side effects of antibiotics include yeast infections, vomiting, nausea, dizziness, abdominal pain, bloating and loss of appetite. Certain antibiotics are associated with skin sensitivity to light, while others can adversely affect the musculoskeletal and nervous systems.
At the population level, antimicrobial resistance is one of the most important global health challenges. Nuanced understanding of the varied mechanisms of bacterial resistance is still emerging. However, there appears to be considerable consensus that slowing down the natural selection of traits that enable human pathogens to survive available treatments requires a reduction in exposure to antibiotics both by cutting down on the number of antibiotic prescriptions and by appropriately limiting the length of antibiotic treatments that do take place.
A number of studies have demonstrated non-inferiority of shorter courses of antibiotics in treating certain conditions. For most conditions, however, there is little to no evidence based on high-quality research. Several ongoing and recently completed studies have investigated biomarker-led early discontinuation of antibiotics. Such results should offer a useful addition to the evidence base. However, not all clinical settings and circumstances are conducive to reliance on biomarkers. Guidance-led fixed-course treatment still has a major role to play in clinical practice.  

Additional commissioning brief background information 

A background document is available that provides further information to support applicants for this call. It is intended to summarise what prompted the call and the existing evidence base, including relevant work from the HTA and wider NIHR research portfolio. It was researched and written on the basis of information from a search of relevant sources and databases, and in consultation with a number of experts in the field. If you would like a copy please email

Making an application 

If you wish to submit a Stage 1 application for this call, the online application form can be found on the Funding opportunities page.  To select this call, use the filters on the right of the screen or search using the call name and/or number.
Your application must be submitted on-line no later than 1pm on the 5th May 2021. Applications will be considered by the HTA Funding Committee at its meeting in July 2021.
Guidance notes and supporting information for HTA Programme applications are available by clicking the links.
IMPORTANT: Shortlisted Stage 1 applicants will be given eight weeks to submit a Stage 2 application. The Stage 2 application will be considered at the Funding Committee in November 2021.
Applications received electronically after 1300 hours on the due date will not be considered.
For commissioned topics, the Programme strongly discourages the practice of the same co-applicant joining more than one competing team. There may be unusual circumstances where the same person could be included on more than on application eg a lead from a named charity or a unique national expert in a condition.
For such exceptions (i) each application needs to state the case as to why the same person is included (ii) the shared co-applicant should not divulge application details between teams and (iii) both teams should acknowledge in their application that they are aware that one of their co-applicants is part of a competing application and that study details have not been shared.
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