TABLE 3.

Gap in evidence for assessing efficacy of single-pill combination therapy vs. free-dose combination therapy

Topic	Evidence gap	Recommendations
Study design	RCTs [only 14% (4/29 in past 5 years)] Long-term prospective studies Outcome studies	Well-designed studies providing a direct comparison between adherence and BP control and/or CV outcomes for studies comparing SPC and free-dose combination therapies Longer-term follow-up to analyze efficacy Consistent recording and reporting of BP
Length of follow-up	Variation in follow-up length and time points made comparisons between studies difficult Few studies reported results beyond six months to one year of follow-up	Multiple and standardized time points should be included in future studies Longer follow-up periods will provide useful information on the long-term adherence benefits of SPC therapy
Assessment of efficacy	Approx. half of studies reported BP measurement or patients reaching BP goals Time to reach BP control not reported How BP was measured was rarely reported	Standard inclusion of BP efficacy measurement(s) Clear definition of time to reach BP control Follow standardized techniques for accurate BP measurement according to up-to-date guidelines Employ ABPM/HPBM/app technology (or similar) to improve assessment of BP out-of-office
Adherence/persistence measure	No standardized reporting of adherence or persistence measurements	Clear and consistent reporting measures for adherence (PDC and MPR are most commonly used) to facilitate comparison between studies Standardized and recommended reporting methodology for persistence Use of validated scales to confirm adherence in specific patient populations
Adverse events	AEs were rarely reported in studies comparing patients receiving SPC and free-combination therapies Few studies reported the grade of AE	Specific studies to determine if increased adherence on SPC therapy is associated with a different safety profile, rather than physicians having to extrapolate information from the safety profile of individual components of the SPC
Patient/physician preferences	Few studies reported patient or physician preferences for SPC or free-combination therapies, or types of antihypertensive medications being prescribed	Evaluate patient preferences for medication type and other factors affecting adherence to aid understanding of preferences around SPC therapy Educate physicians’ treatment decisions as increased importance is being placed on patient preferences across all aspects of health care

ABPM, ambulatory blood pressure monitoring; AE, adverse event; BP, blood pressure; CV, cardiovascular; HBPM, home blood pressure monitoring; MPR, medication possession ratio; PDC, proportion of days covered; RCT, randomized controlled trial; SPC, single-pill combination.