Most people with a health condition are excluded from research trials examining how well a medicine works to treat their condition. Common reasons to be excluded from such research trials are often based upon age, gender, people having other health conditions (comorbidity), and people prescribed other medicines (co-prescribing). Clinical guidelines are commonly used by doctors and other clinicians to guide treatment decisions, but most guideline development focused on evidence for a single disease, and does not usually explicitly consider the whether or not patients have other conditions (comorbidity) or are already being prescribed other medicines (co-prescribing). A key reason for this is that guideline developers do not have access to important information about the clinical population they are making recommendations for. We will examine how commonly people in the population have different numbers of chronic conditions and are prescribed different numbers of medicines including how this varies by age and gender (which are key reasons for exclusion from research trials). We will then examine how people excluded from key research trials differ from people included in trials in terms of comorbidity, co-prescribing, how frail they are, and their chance of survival. We will then work guideline developers to explore how summaries of this information could be used during guideline development.
We will examine the prevalence of multimorbidity (defined as having two or more health conditions), and polypharmacy (defined by the total number of drugs currently prescribed using existing commonly used cut-offs of 5+, 10+ and 15+ drugs) among a cross-section of patients acceptable for use in research within CPRD, including examining how prevalence varies by age, gender, and socioeconomic deprivation. We will then define patients with both prevalent and recently diagnosed index conditions and determine whether they would have been eligible for inclusion in clinical trials of treatments for that index condition that are relevant to clinical guidelines. For each index condition, we will then compare those eligible and those ineligible in terms of:
- The proportion of patients that would have been eligible for each clinical trial of treatment;
- Differences in patient characteristics in terms of the total number of comorbidities, the number of concordant and discordant comorbidities, the number of physical and mental health comorbidities, frailty measured by the electronic Frailty Index, weighted comorbidity measured by the Charlson Index, prescribing drug count/polypharmacy, and A&E attendance (stratified by age, gender, ethnicity, and socioeconomic deprivation)
- The prevalence of significant interactions between the drug evaluated by the trial and comorbidities based on advice about relative and absolute contraindications to the target drug
- The prevalence of significant interactions between the drug evaluated by the trial and currently co-prescribed drugs based on identified interactions with potentially serious consequences
- Rates of common adverse events of the drug evaluated by the trial (eg falls and injury related to falls, bleeding, constipation, acute kidney injury, postural hypotension or low blood pressure)
- Mortality from the index condition and other health conditions over different pre-specified time periods.
Initial descriptive analysis
(1) Prevalence of multimorbidity defined as two or more chronic conditions, and defined as ‘complex multimorbidity’ using definitions proposed in the literature (eg 3+ chronic conditions, 3+ conditions from 3+ body systems, physical-mental health multimorbidity)
(2) Prevalence of polypharmacy defined as 5+, 10+ and 15+ drug classes prescribed in the previous 56 days
Examination by trial exclusion
(1) The prevalence of comorbidity (total number or comorbidities; number of concordant and discordant comorbidities; number of physical and mental health comorbidities);
(2) The prevalence of co-prescribing (total number of drugs currently prescribed; number from a different BNF chapter than the index condition);
(3) The electronic Frailty Index score and Charlson Index (both are cumulative morbidity scores which are predictive of future mortality, hospital admission and care home admission);
(4) The prevalence of significant interactions between the drug evaluated by the trial (if applicable) and comorbidities (based on British National Formulary [BNF] advice about relative and absolute contraindications to the target drug);
(5) The prevalence of significant interactions between the drug evaluated by the trial (if applicable) and currently co-prescribed drugs (based on BNF identified interactions with potentially serious consequences);
(6) Rates of common adverse drug effects (eg falls and injury related to falls, bleeding, constipation, acute kidney injury, postural hypotension or low blood pressure)
(7) Mortality from the index condition and from other conditions.
Bruce Guthrie - Chief Investigator - University of Edinburgh
Bruce Guthrie - Corresponding Applicant - University of Edinburgh
Chris Hall - Collaborator - University of Dundee
Clare MacRae - Collaborator - University of Edinburgh
Daniel Morales - Collaborator - University of Dundee
David McAllister - Collaborator - University of Glasgow
David Moreno Martos - Collaborator - University of Dundee
Emily Jefferson - Collaborator - University of Dundee
Magalie Guignard-Duff - Collaborator - University of Dundee
Megan McMinn - Collaborator - University of Edinburgh
Shahzad Mumtaz - Collaborator - University of Dundee
Sohan Seth - Collaborator - University of Edinburgh
Stewart Mercer - Collaborator - University of Edinburgh
Zsolt Szarka - Collaborator - University of Dundee
Chuang Gao - Collaborator - University of Dundee
Scott Horban - Collaborator - University of Dundee
HES Accident and Emergency;HES Admitted Patient Care;ONS Death Registration Data;Patient Level Index of Multiple Deprivation;Practice Level Index of Multiple Deprivation