Table 1.

Evidence to recommendations table: Does deprescribing PPIs (dose reduction, on-demand use, abrupt discontinuation, stepping down to H₂RA therapy) compared with continuous PPI use result in benefits or harms for adults > 18 y (excluding those with history of bleeding ulcer, Barrett esophagus, and severe esophagitis grade C and D) in primary care and long-term care settings?

DECISION DOMAIN	SUMMARY OF REASON FOR DECISION	SUBDOMAINS INFLUENCING DECISION
QoE: Is there high- or moderate-quality evidence Yes □ No ☑ (See references 1–16 in the evidence reviews at CFPlus^*)	The QoE for symptom relapse with deprescribing is low Low-dose PPIs did not lead to significantly greater relapses than standard-dose PPIs did (RR = 1.16, 95% CI 0.93 to 1.44); on-demand PPI use and step down to an H₂RA increased risk of symptom relapse compared with continuous PPI use (RR = 1.71, 95% CI 1.31 to 2.23, and RR = 1.92, 95% CI 1.44 to 2.58, respectively)	QoE for benefits with on-demand use: moderate Lower pill burden: 3.5 fewer pills per week (95% CI −4.89 to −2.18)
Balance of benefits and harms: Is there certainty that the benefits outweigh the harms? Yes ☑ No □ (See the description of harms and references 17–20 in the evidence reviews at CFPlus^*)	Our systematic review showed that low-dose PPIs did not lead to a significantly higher GI relapse rate compared with standard doses. On-demand PPI use reduced pill burden. Cost, rare PPI side effects, and drug interactions were noted as potential concerns for continuous PPI use. Low-dose PPIs were thus considered to clearly have greater benefits than harms. On-demand PPI use and a step-down approach to H₂RAs were also noted to have benefits over harms, but this was not as certain as the other deprescribing approach	Is the baseline risk for benefit similar across subgroups? Yes ☑ No □ No evidence that benefits are different in subgroups Should there be separate recommendations for subgroups based on risk levels? Yes □ No ☑ No evidence of benefit for any risk level Is the baseline risk for harm similar across subgroups? Yes ☑ No □ No evidence that harms would be different for subgroups Should there be separate recommendations for subgroups based on harms? Yes □ No ☑ No evidence for harms in subgroups
Values and preferences: Is there confidence in the estimate of relative importance of outcomes and patient preferences? Yes □ No ☑ (See references 1–3 and 21–25 in the evidence reviews at CFPlus^*)	In semistructured interviews patients reported that they believed PPIs were effective for preventing GI symptoms. However, it was also noted that most patients with GERD do not take their PPIs on a regular basis, and this has led to on-demand PPI research. Dose-lowering studies did not report patient satisfaction, while on-demand studies did not provide clear evidence on patient satisfaction	Perspective taken: the guideline group put high value on the lack of evidence of serious harms of deprescribing and on the reduction of medications and related harms and medication costs. Less value was placed on lack of information to determine the variability of patient values and preferences on different deprescribing approaches Source of values and preferences: semistructured interviews and other qualitative studies Source of variability, if any: variability difficult to estimate Method for determining values satisfactory for this recommendation? Yes ☑ No □ Clear preference to use PPIs to prevent GERD, but also evidence for on-demand and other reduced-dose use All critical outcomes measured? Yes ☑ No □ More information on the various describing approaches would be helpful, but available evidence was clear
Resource implications: Are the resources worth the expected net benefit? Yes ☑ No □ (See references 19 and 26–39 in the evidence reviews at CFPlus^*)	In Canada, PPI use accounts for a high proportion of public drug program spending ($249.6 million in 2013). The recommended treatment duration for GERD, the most common GI symptom, is 4 wk; thus much of this PPI use is inappropriate. Several studies have demonstrated interventions to reduce PPIs are feasible. On-demand trials led to reduced pill burden. The cost of stopping PPIs, however, should be balanced against possible increased visits to physicians. Cost-effectiveness analyses were not available	Feasibility: Is this intervention generally available? Yes ☑ No □ Opportunity cost: Is this intervention and its effects worth withdrawing or not allocating resources from other interventions? Yes ☑ No □ The budget for PPIs is $69 million, and inappropriate PPI use is a considerable problem in adults and the elderly Is there a lot of variability in resource requirements across settings? Yes □ No ☑ Deprescribing guidelines and implementation were considered to have relatively low resource requirements and to be feasible in primary care and long-term care
Strength of main recommendation: strong	Based on the lack of evidence of harm, the evidence for benefits of reducing inappropriate PPI use, the societal cost of inappropriate PPI use, and the feasibility of this intervention in primary care and long-term care
Remarks and values and preference statement	The strong recommendation refers to low-dose or on-demand (as needed) PPI use. The weak recommendation refers to stepping down to H₂RA therapy as a deprescribing approach. These recommendations place high value on zero to minimal clinical risk of deprescribing and on the inappropriate use of PPIs and resources, given the high cost associated with long-term PPI use, and some value on the potential harms and remote side effects (eg, pneumonia, diarrhea, Clostridium difficile, osteoporosis)

GERD—gastroesophageal reflux disease, GI—gastrointestinal, H₂RA—histamine-2 receptor antagonist, PPI—proton pump inhibitor, QoE—quality of evidence, RR—relative risk.