Evaluating Vonoprazan and Tegoprazan for Gastroesophageal Reflux Disease Treatment in Chinese Healthcare: An EVIDEM Framework Analysis

doi:10.21203/rs.3.rs-3930251/v1

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Research Article

Evaluating Vonoprazan and Tegoprazan for Gastroesophageal Reflux Disease Treatment in Chinese Healthcare: An EVIDEM Framework Analysis

https://doi.org/10.21203/rs.3.rs-3930251/v1

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Journal Publication

published 20 Jun, 2024

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Background

In Chinese healthcare settings, decisions regarding drug selection are predominantly guided by the Pharmacy & Therapeutics Committee (PTC). This study focuses on two recently introduced potassium-competitive acid blockers in China, vonoprazan (VPZ) and tegoprazan (TPZ). The objective was to assess these drugs using the Evidence and Value: Impact on DEcisionMaking (EVIDEM) framework.

Methods

This study utilized the 10th edition of EVIDEM, comprising a core model with five domains and 13 criteria. It involved two independent expert panels. The PTC expert panel was tasked with five responsibilities: assigning weights using a 5-point scale, defining scoring indicators, examining the evidence matrix, scoring, and decision-making. The evidence matrix expert panel had three duties: conducting a systematic literature review, creating the evidence matrix, and evaluating the value contributions of VPZ and TPZ.

Results

The analysis estimated the value contributions of VPZ and TPZ at 0.59 and 0.54, respectively. The 'economic consequences of intervention' domain exhibited the most significant variation in value contribution between the two drugs, followed by 'comparative outcomes of intervention' and 'type of benefit of intervention'.

Conclusion

Utilizing the EVIDEM framework, VPZ's value contribution appears marginally superior to that of TPZ. The EVIDEM framework shows promise for application in Chinese medical institutions.

EVIDEM

Hospital-based health technology assessment

vonoprazan

tegoprazan

In Chinese medical institutions, the Pharmacy & Therapeutics Committee (PTC) regularly encounters the intricate task of choosing the most suitable medications. The process of selecting drugs is multifaceted, involving various criteria, stakeholders, and values[1]. Initial clinical evidence is typically supplied by pharmaceutical companies, and the quantity and quality of this data present challenges to the PTC when making decisions[2]. Beyond the evidence, decision-making also entails making value judgments. Disagreements in this process can emerge from differing perspectives on the role of evidence and judgment in evidence-based medical decision-making[3]. Moreover, the PTC in Chinese medical institutions is often required to make swift decisions. Therefore, there is an urgent need for decision support tools to aid the PTC.

The Evidence and Value: Impact on DEcisionMaking (EVIDEM) framework, developed by Goetghebeur et al., consists of a central model comprising five domains and 13 criteria, providing a structured approach to prioritization[4]. It allows decision-makers to express their values by assigning weights to various decision criteria. The results of these evaluations are converted into value estimates through a process of weighting and scoring. The mathematical components of the EVIDEM framework are designed to enhance the clarity, expression, and sharing of individual reasoning. EVIDEM bridges the gap between health technology assessment (HTA) and effective healthcare decision-making through multicriteria decision analysis (MCDA)[5]. Rooted in real-life deliberation and decision-making, EVIDEM helps enhance the consistency, transparency, and legitimacy of decision-making and has diverse applications in healthcare[6]. EVIDEM offers a nuanced and adaptable tool tailored to the intricate decision-making processes in medical institutions.

Numerous drugs are available to manage gastroesophageal reflux disease (GERD), including those that suppress acid production. Proton pump inhibitors (PPIs) are the primary treatment for GERD[7, 8]. Nevertheless, the limitations of PPI therapy cannot be disregarded, such as PPI-refractory, nocturnal acid breakthrough (NAB), and genetic polymorphism[9]. Potassium-competitive acid blockers (P-CABs) represent a novel class of acid suppressants, with vonoprazan (VPZ) and tegoprazan (TPZ) being the available P-CABs in China. These drugs offer several advantages over PPIs, including rapid onset of action and prolonged acid suppression[10]. However, despite the increasing availability of VPZ and TPZ in the market, a comprehensive assessment of their comparative effectiveness and overall value within the Chinese healthcare context remains unexplored. This study aims to assess VPZ and TPZ using the EVIDEM framework. By utilizing the EVIDEM framework, we anticipate uncovering insights that could significantly impact the strategic drug selection and policy-making processes for GERD treatment in Chinese healthcare settings. The results are expected to offer a nuanced insight into the value contribution of these drugs, potentially guiding more informed and efficient healthcare decisions. This could have far-reaching implications, including improved patient outcomes, optimized resource utilization, and potential changes in prescribing practices. Ultimately, this study aims to offer evidence-based guidance to healthcare professionals and policymakers.

EVIDEM framework source

The study employed the 10th edition of the EVIDEM framework, which has evolved over a decade of open-source development and is officially published[6]. This edition encompasses a core model with five domains and 13 criteria, as detailed in Table 1.

Table 1

The Evidence and Value: Impact on DEcisionMaking framework
Domains	Criteria	Type	Scoring Scale High→Low	Indicators
Need for intervention	Disease severity	Absolute	5 4 3 2 1 0 Very severe→Not severe	Morbidity, Progression, Quality of life
	Size of the affected population	Absolute	5 4 3 2 1 0 Common diseases→Very rare diseases	Disease incidence
	Unmet needs	Absolute	5 4 3 2 1 0 Many unmet needs→No unmet needs	Compliance, Response rate, Nocturnal acid breakthrough, Genetic polymorphism
Comparative outcomes of intervention	Comparative effectiveness	Relative	5 4 3 2 1 0–1 -2 -3 -4 -5 Much better than the comparator→No difference→Much worse than the comparator	Reflux esophagitis healing rate, Intragastric pH
	Comparative safety	Relative		Incidence of adverse effects
	Comparative patient-perceived health	Relative		Heartburn
Type of benefit of intervention	Type of preventive benefit	Absolute	5 4 3 2 1 0 Eradication→No preventive benefit	Preventive benefit
Type of benefit of intervention	Type of therapeutic benefit	Absolute	5 4 3 2 1 0 Cure→No therapeutic benefit	Therapeutic benefit
Economic consequences of intervention	Comparative cost consequences—costs of intervention	Relative	5 4 3 2 1 0–1 -2 -3 -4 -5 Substantial savings/Good affordability→No change in spending→Substantial additional expenditures/Bad affordability	Drug cost
	Comparative cost consequences—other medical costs	Relative		Pharmacoeconomic research in China
	Comparative cost consequences—non-medical costs	Relative		Pharmacoeconomic research in China
Knowledge about intervention	Quality of evidence	Absolute	5 4 3 2 1 0 Highly relevant and valid→Not relevant and/or invalid	Type of evidence, Level of evidence
Knowledge about intervention	Expert consensus/clinical practice guidelines	Absolute	5 4 3 2 1 0 Strong recommendation for intervention above all other alternatives→Not recommended or invalid	Recommendation

Expert panel design and duty

The study engaged two distinct expert groups: the PTC expert panel and the evidence matrix expert panel.

The selection of experts for the PTC panel was a highly meticulous process, aimed at covering a wide spectrum of expertise essential for a comprehensive evaluation of the drugs under consideration. This approach was also aligned with the legal requirements for the PTC in China. The panel consisted of fourteen members, and each member was deliberately chosen to represent various domains, including pharmacy, gastroenterology clinical medicine, nursing, hospital infection management, hospital health insurance, hospital quality control and healthcare management. This careful selection resulted in two experts from each of these areas. This diversity was of utmost importance to ensure a thorough assessment from multiple healthcare perspectives. By incorporating such a diverse range of expertise, it was guaranteed that every aspect of drug evaluation, from clinical effectiveness to practical implementation, received thorough consideration. This inclusive approach significantly enhanced the strength and credibility of the study's findings, as it allowed for a more holistic and well-rounded examination of the drugs in question. The PTC experts conducted two offline meetings, fulfilling five key tasks. In the initial meeting, after thorough familiarization with the EVIDEM framework, the panel set weights for the 13 criteria on a 5-point scale (see Table 2) and developed evaluation indicators for these criteria (refer to Table 1). Following the completion of the evidence matrix, a second meeting was convened to review it. The PTC expert panel assigned scores to the 13 criteria based on the evidence matrix and then proceeded to make a drug selection decision. This decision was based on the value contributions of VPZ and TPZ as calculated by the evidence matrix expert panel. The decision-making process is illustrated in Fig. 1.

Table 2

Weighting tool
Weight
5 High impact on the value of medicines (decisive)
4
3
2
1 Very low impact on the value of medicines (inessential)

Figure 1 PTC decision-making process.

Notes: PTC, Pharmacy & Therapeutics Committee; EVIDEM, Evidence and Value: Impact on DEcisionMaking

The evidence matrix expert panel, composed of three experts in evidence-based medicine, was assigned three primary tasks: (1) conducting a systematic literature review based on the indicators defined by the PTC expert panel, (2) creating the evidence matrix, and (3) calculating the value contributions of VPZ and TPZ.

Literature review and evidence matrix

A thorough literature review was undertaken to gather available evidence concerning the 13 criteria for VPZ and TPZ within the EVIDEM framework. This search utilized major biomedical databases such as PubMed, Embase, The Cochrane Library, and China Biology Medicine disc, covering literature up to June 2023. The review was limited to Chinese and English language publications. In the domain related to the 'need for intervention', our search terms encompassed the following keywords: vonoprazan, tegoprazan, gastroesophageal reflux disease, esophagitis, quality of life, epidemiology/prevalence/incidence, mortality, and proton pump inhibitor. For both 'comparative outcomes of intervention' and 'type of benefit of intervention' domains, our search criteria included the following terms: vonoprazan, tegoprazan, gastroesophageal reflux disease, esophagitis, efficacy, safety, and all relevant clinical studies were selected and compiled based on the evaluation indicators. For pharmacoeconomic research specific to China, only studies conducted within the Chinese context were considered. For the 'knowledge about intervention' domain, our search strategy encompassed keywords such as gastroesophageal reflux disease, esophagitis, guidelines, recommendations, and clinical practice. The compiled evidence was systematically organized into evidence matrices (see Supplementary file 1), which were subsequently reviewed by the expert panel.

Data analysis

The overall estimated value contributions of VPZ and TPZ were determined using an additive linear model.

where V is the total estimated value, n is the number of experts, Vx is the value contribution of criterion x, Wx is the weighting of criterion x, ΣWn is the sum of all weights, and Sx is the normalized score for each criterion x (Sx = score/5).

Weights of 13 criteria

The PTC expert panel established weights for each criterion in a single meeting, as depicted in Fig. 2. In the domain of 'need for intervention', 'unmet needs' received the highest average weight. Comparative effectiveness and safety were equally weighted. Experts in medical institutions focused on the therapeutic benefits of the drugs under evaluation. Within the domain of 'economic consequences of intervention', costs of intervention > other medical costs > non-medical costs. The quality of evidence criterion showed significant variability in weighting.

Figure 2 Weights for 13 criteria

Scores based on the evidence matrix

Table 3 summarizes the scores and key observations for all 13 criteria for VPZ and TPZ. The detailed evidence matrix is provided in Supplementary file 1.

Table 3

Scores and key comments of 13 criteria for VPZ and TPZ
Criteria	Scores (mean ± SD)	Comments
Disease severity	2.9 ± 0.6	Morbidity: There was no elevated risk of all-cause mortality associated with GERD. Progression: Most patients remained stable or showed improvement in their grade of esophagitis in 5 years. There was a positive association between reflux symptoms and the risk of esophageal adenocarcinoma. Quality of life: Respondents with GERD experienced heartburn, eating and drinking problems, sleep impairment, reduced work productivity, etc.
Size of the affected population	3.5 ± 1.1	Age-standardized prevalence of GERD in China is below 5%. Around 3,000 patients annually have been diagnosed with GERD in the study's host hospital.
Unmet needs	4.2 ± 0.6	PPI response rate: 10–54% of patients with GERD symptoms failed to respond to a standard-dose PPI. PPI compliance: PPIs are used before meals and take 3–5 days to achieve a steady-state antisecretory effect. Nocturnal acid breakthrough: More than 70% of patients treated with PPIs had NAB. Genetic polymorphism: CYP2C19 genetic polymorphism causes significant inter-individual pharmacodynamic variability with PPI treatment.
Comparative effectiveness	VPZ 3.9 ± 1.1 TPZ 3.4 ± 1.0	VPZ and TPZ are non-inferior to PPIs for patients with GERD. VPZ may be more effective than PPIs for severe erosive esophagitis. Nocturnal pH ≥ 4 HTRs of VPZ and TPZ were greater than PPIs. 24-hour pH ≥ 4 HTRs of VPZ were greater than PPIs. The acid inhibitory effects of VPZ and TPZ are irrespective of the CYP2C19 genotype.
Comparative safety	VPZ 3.0 ± 0.6 TPZ 3.1 ± 0.5	Safety of VPZ and TPZ is comparable with PPIs.
Comparative patient-perceived health	VPZ 2.5 ± 1.0 TPZ 2.4 ± 1.2	There were no substantial differences in improvement of heartburn between VPZ and PPIs. Nocturnal heartburn improvement of VPZ and TPZ was greater than PPIs.
Type of preventive benefit	VPZ 3.6 ± 0.9 TPZ 3.4 ± 1.0	Long-term maintenance therapy and on-demand therapy with VPZ and TPZ can reduce the GERD recurrence rate.
Type of therapeutic benefit	VPZ 4.1 ± 0.9 TPZ 3.8 ± 1.1	The therapeutic target is to relieve symptoms, heal, prevent complications, and improve health-related quality of life. The therapeutic effect is mainly shown in improvement of reflux esophagitis healing rate, GerdQ/FSSG/GOS scores, heartburn symptoms, etc.
Costs of intervention	VPZ 0.9 ± 0.7 TPZ − 0.6 ± 0.5	In 2022, China's per capita disposable income reached ¥36,883. The treatment phase takes 8 weeks, VPZ costs ¥558.88, and TPZ costs ¥626.08. The maintenance phase, VPZ costs ¥4.945 daily, TPZ costs ¥5.59 daily.
Other medical costs	VPZ 1.3 ± 0.9 TPZ 0	VPZ generates incremental QALYs at a lower cost compared with PPIs. TPZ retrieved no evidence.
Non-medical costs	VPZ 0 TPZ 0	Neither VPZ nor TPZ retrieved evidence.
Quality of evidence	2.4 ± 0.7	The quality of evidence on which the comparison data are based is highly relevant and valid. There is still a lack of direct comparisons between VPZ and TPZ.
Expert consensus/clinical practice guidelines	3.5 ± 1.0	The results of the current expert opinions and clinical practice guidelines clearly indicate that PPIs and P-CABs are the first-line treatment for GERD.
Notes: VPZ, vonoprazan; TPZ, tegoprazan; GERD, gastroesophageal reflux disease; NAB, nocturnal acid breakthrough; PPIs, proton-pump inhibitors; CYP2C19, cytochrome P450 2C19; pH ≥ 4 HTR, pH ≥ 4 holding time ratio; GerdQ, GERD questionnaire; FSSG, Frequency Scale for the Symptoms of GERD; GOS, Global Overall Symptom; QALYs, quality adjusted life years; P-CABs, potassium-competitive acid blockers.

Need for intervention domain

In the 'need for intervention' domain, the criterion of 'disease severity' received an average score of 2.9 ± 0.6, suggesting that the experts did not consider GERD to be particularly severe, despite its significant impact on patients' quality of life, work, and emotional well-being[11].

The 'size of the affected population' criterion scored higher than 'disease severity'. Although GERD incidence in China is lower compared to Europe and North America[12], the absolute number of patients remains substantial due to China's large population. This was evidenced by approximately 3,000 diagnosed cases annually in the study's host hospital. The criterion received an average score of 3.5 ± 1.1.

The 'unmet needs' criterion scored the highest among the 13 indicators with an average of 4.2 ± 0.6, indicating a significant unmet need for alternatives to PPI-based acid suppression therapy.

Comparative outcomes of intervention domain

For the 'comparative effectiveness' criterion, key indicators included reflux esophagitis (RE) healing rate and pH ≥ 4 holding time ratios (HTRs). Both VPZ and TPZ showed over 90% esophageal healing rates in erosive esophagitis (EE) patients after eight weeks, comparable to PPIs[13–16]. However, VPZ may exhibit greater effectiveness compared to PPIs, particularly in cases of severe EE[13–15], where it has demonstrated higher efficacy. In terms of nocturnal pH ≥ 4 HTRs, both VPZ and TPZ outperformed PPIs[17–21]. A separate study comparing TPZ and VPZ reported a treatment success rate of 66.0% for TPZ and 60.5% for VPZ, with a p-value of 0.30, indicating no statistically significant difference between the two[20]. During the 0–24 hour period, pH ≥ 4 HTRs displayed variations. Three studies indicated significantly more favorable outcomes for the 20 mg VPZ compared to PPIs[17–19], whereas the results for the 50 mg TPZ group were similar to those of the PPIs[20, 21]. The experts concluded that the outcomes mentioned above favored VPZ over TPZ. On average, the scores given to VPZ and TPZ were 3.9 ± 1.1 and 3.4 ± 1.0, respectively.

Recent systematic reviews have revealed no significant differences in the occurrence of adverse events (AEs) among patients using VPZ compared to those on PPIs. Specifically, the incidences of any AEs (Odds ratio [OR] = 0.96, p = 0.66), drug-related AEs (OR = 1.10, p = 0.44), serious AEs (OR = 1.14, p = 0.36), and AEs leading to drug discontinuation (OR = 1.09, p = 0.55) were comparable between VPZ and PPIs[22]. Similarly, meta-analyses of TPZ, based on four clinical trials[16, 23–25], showed no significant differences in the incidences of any AEs (OR = 0.79, p = 0.22), drug-related AEs (OR = 0.82, p = 0.47), and serious AEs (OR = 2.25, p = 0.30) when compared to PPIs. The overall average scores for VPZ and TPZ on the 'comparative safety' criterion were 3.0 ± 0.6 and 3.1 ± 0.5, respectively, indicating no significant disparity in safety profiles according to experts.

Regarding heartburn symptoms, differences between VPZ and TPZ were noted. The percentages of 24-hour heartburn-free periods for VPZ 20 mg and esomeprazole 40 mg were 36.7% and 38.4%, respectively, without statistical significance[26]. Nevertheless, VPZ demonstrated superior efficacy in achieving complete nocturnal heartburn relief compared to lansoprazole (p < 0.01)[27]. In contrast, TPZ showed significantly higher complete resolution rates of heartburn than placebo[28], but its efficacy in terms of the time to the first nighttime heartburn-free interval and the percentage of nighttime heartburn-free days was similar to esomeprazole[24]. The overall average scores for VPZ and TPZ in the 'comparative patient-perceived health' criterion were 2.5 ± 1.0 and 2.4 ± 1.2, respectively.

Type of benefit of intervention domain

In the 'type of benefit of intervention' domain, the 'type of preventive benefit' criterion received average scores of 3.6 ± 0.9 for VPZ and 3.4 ± 1.0 for TPZ. This reflects a consensus among experts that both VPZ and TPZ offer considerable preventive benefits, particularly in achieving high endoscopic remission rates. Data available for maintenance therapy shows VPZ's effectiveness for up to 52 weeks[29] and TPZ's for 24 weeks[25]. Notably, VPZ at a dose of 10 mg proved clinically effective in maintaining healed RE refractory to PPIs for 48 weeks[30].

The 'type of therapeutic benefit' criterion was scored 4.1 ± 0.9 for VPZ and 3.8 ± 1.1 for TPZ. These scores highlight the therapeutic advantages of both drugs, especially in improving the RE healing rate, as well as in enhancing GERD Questionnaire (GerdQ)/Frequency Scale for the Symptoms of GERD (FSSG)/Global Overall Symptom (GOS) scores, and alleviating heartburn symptoms. A key observation is that compared with PPIs, VPZ and TPZ demonstrated a faster onset of action and inhibited acid production irrespective of CYP2C19 genotype variations[20, 31]. Furthermore, VPZ was particularly effective for patients resistant to PPI-based RE treatment[32].

Economic consequences of intervention domain

The economic consequences were assessed based on three criteria, starting with the 'costs of intervention'. In China, the treatment phase cost for VPZ is ¥558.88, while for TPZ, it is ¥626.08. These costs represent approximately 1.5% and 1.7%, respectively, of China's per capita disposable income in 2022. Experts suggest that both drugs are relatively affordable for patients, with VPZ being slightly more economical. The average scores for VPZ and TPZ in this criterion were 0.9 ± 0.7 and − 0.6 ± 0.5, respectively.

A single study evaluated the cost-effectiveness of VPZ compared to PPIs in treating GERD patients in China. 'Other medical costs' mainly includes expenses for outpatient visits, endoscopies, and 24-hour pH monitoring[33]. This study concluded that VPZ is the dominant treatment option in terms of cost-effectiveness. Regarding 'other medical costs', VPZ and TPZ scored 1.3 ± 0.9 and 0, respectively.

No data were available to evaluate the 'non-medical costs', and hence the PTC expert panel did not assign scores to this criterion.

Knowledge about intervention domain

All clinical trials included in this review were deemed valid. However, there is a notable absence of direct comparisons between VPZ and TPZ. Consequently, the 'quality of evidence' criterion received a score of 2.4 ± 0.7, reflecting its relative lesser significance.

The final criterion appraised was 'expert consensus/clinical practice guidelines', which scored 3.5 ± 1.0. Despite PPIs remaining the predominant treatment for GERD, P-CABs have been increasingly recommended in clinical practice guidelines as a first-line treatment[34, 35]. Additionally, P-CABs have been recognized for their superior efficacy in controlling intragastric pH more effectively and rapidly than PPIs, particularly in cases of refractory GERD[9].

Estimated value contribution of VPZ and TPZ

The estimated value contributions for VPZ and TPZ were 0.59 and 0.54, respectively. Figure 3 illustrates the estimated value contributions across the five domains. The 'economic consequences of intervention' domain exhibited the most significant difference in value contribution between VPZ and TPZ, followed by the 'comparative outcomes of intervention' and 'type of benefit of intervention' domains.

Figure 3 Estimated value contribution of vonoprazan (VPZ) and tegoprazan (TPZ)

In the context of GERD management, PPIs are still the most primary drug treatment[7, 8]. Notably, up to 40% of GERD patients continue to experience symptoms despite PPI treatment[9]. Both PPIs and P-CABs target H⁺/K⁺-ATPase to inhibit acid secretion. As an alternative to PPIs, P-CABs have demonstrated their ability to suppress acid production by competitively inhibiting the gastric H⁺/K⁺-ATPase through K⁺ competition[10]. They also offer a prolonged inhibition with a gradual dissociation from the H⁺/K⁺-ATPase, resulting in long-lasting effects[36]. A clinical study with 24 patients with PPI-resistant RE reported a 87.5% success rate in treating esophageal mucosal breaks with 20 mg of VPZ[32]. Furthermore, NAB is a common occurrence, even when PPIs are administered twice daily. NAB is observed in over 70% of Helicobacter pylori-negative patients undergoing PPI therapy[37]. VPZ and TPZ have demonstrated more effective nighttime acid suppression compared to PPIs[17–21]. Additionally, there exists a substantial variation in pharmacodynamic responses among individuals, primarily attributed to CYP2C19 genetic polymorphism, which influences its impact on pharmacokinetics. Research has demonstrated that individuals classified as poor metabolizers based on their CYP2C19 enzyme activity are more prevalent in Asian populations (8–20%) when compared to Caucasians (3–5%) and African Americans (3–5%)[38]. Unlike PPIs, VPZ and TPZ's efficacy in acid suppression is not dependent on the CYP2C19 phenotype[20, 31]. Finally, it is worth noting that PPIs are susceptible to degradation in acidic conditions and typically require enteric coating, leading to delayed absorption and onset of action[9]. However, clinical studies have indicated that VPZ and TPZ can be administered without the need to consider food intake[39, 40]. VPZ and TPZ address certain unmet needs in PPIs and provide a new option for the clinical management of GERD.

When it comes to evaluating relative indicators, our preference was to have data from trials directly comparing VPZ and TPZ. Unfortunately, only one such trial was available[20]. Consequently, for most of the relative criteria, we had to use PPIs as a reference to indirectly compare VPZ and TPZ. This choice inevitably diminishes the quality of evidence and underscores the importance of sharing and communication. Following extensive discussions and in order to minimize the influence of personal biases and potential conflicts of interest, the experts reached a consensus on how to score the relative indicators. Scores should be determined based on results from studies comparing VPZ and TPZ with PPIs. If there is no significant difference between VPZ and TPZ when compared to PPIs, the score difference should not exceed 1 point. However, if there is a discernible distinction between VPZ and TPZ in relation to PPIs, a score difference of more than 1 point should only be assigned when taking into consideration the overall benefits and drawbacks to the patient. For example, in the assessment of the 'comparative effectiveness' criterion, VPZ and TPZ exhibited comparable results to PPIs in terms of RE healing rate and nocturnal pH ≥ 4 HTRs^[13–21]. Nevertheless, VPZ demonstrated higher efficacy in severe EE cases^[13–16] and more favorable 0–24 hour pH ≥ 4 HTRs compared to PPIs^[17–19], whereas TPZ's results were similar to those of PPIs[20, 21]. Given these considerations, it is more likely that patients will benefit from VPZ in terms of efficacy, resulting in scores of 3.9 ± 1.1 and 3.4 ± 1.0 for VPZ and TPZ, respectively.

This study elucidated the multifaceted process involved in drug selection when evaluating VPZ and TPZ for GERD treatment. It marked the first instance of our medical institution employing the EVIDEM framework to support drug selection decisions, an approach that has only been reported once before in China[1]. The EVIDEM framework serves as a bridge between evidence and decision-making. All PTC experts expressed confidence in the evaluation results and looked forward to its continued use. They also deliberated on the evidence matrix and the potential implications of the evaluation results for clinical practice.

The experts unanimously recognized that respecting patients' wishes and values is a fundamental prerequisite for prescribing. Taking the patient's perspective into account is especially important when prescribing P-CABs for patients who are PPI-refractory[32], experience NAB[17–21], possess specific CYP2C19 genotypes indicative of rapid metabolism[20, 31], or have difficulties adhering to premeal dosing[39, 40]. For example, VPZ should be prescribed for patients with EE and for those who prioritize economic considerations. Prioritizing the patient's viewpoint reflects the principles of respecting patient autonomy and dignity, both of which are integral aspects of the healthcare system, as emphasized in articulated principles[41].

The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) Working Group has also acknowledged the importance of incorporating patients' values and wishes into clinical evidence-based guidelines[42]. Furthermore, the PTC experts explored the possibility of introducing a minimum of two patient representatives, a practice that has not been previously reported in drug selection decisions within Chinese medical institutions.

Although this study lays an important foundation for the PTC in making drug selection decisions, it exhibits several limitations. Primarily, the absence of direct clinical trials comparing VPZ and TPZ necessitated the use of PPIs as the comparator. This approach permits only indirect comparisons, thereby diminishing the 'quality of evidence', which was scored at 2.4 ± 0.7. Furthermore, by focusing exclusively on pharmacoeconomic studies conducted in China, the research encounters two significant challenges: a limited evidence base and a narrow view of the broader pharmacoeconomic discussion. The PTC expert panel also did not evaluate the 'non-medical costs'. Finally, the absence of an expert panel for monitoring and maintaining the quality of evidence is an aspect that needs improvement in future research.

Utilizing the EVIDEM framework, this study estimates that the value contribution of VPZ is marginally higher than that of TPZ. The EVIDEM decision framework effectively converts evidence-based information into a quantifiable drug value assessment. This process facilitates the comparison and ranking of drugs, aiding decision-makers in making informed, scientific choices. Given its efficacy, the EVIDEM framework holds considerable promise for adoption in medical institutions.

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Availability of data and materials

All items are included in Additional file 1. The datasets are available from the corresponding author on reasonable request.

Competing interests

The authors declare no competing interests.

Funding

This work was supported by China International Medical Foundation (Z-2021-46-2101). The funding body was not involved in the study design, data collection, analysis of data and writing of the manuscript.

Authors' contributions

ZJD was responsible for the design of the study. YHD, HTY and HXJ performed the data collection. NBR and YZ analyzed the data. CJX obtained funding and drafted the manuscript. All authors critically revised the manuscript for important intellectual content and approved the final version for publication.

Acknowledgements

The authors would like to thank all of the experts who participated in the study.

The technical support of EVIDEM provided by Professor Jinsong Geng from Nantong University Medical School is greatly appreciated.

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No competing interests reported.

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Evaluating Vonoprazan and Tegoprazan for Gastroesophageal Reflux Disease Treatment in Chinese Healthcare: An EVIDEM Framework Analysis

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Abstract

Background

Methods

Results

Conclusion

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Background

Methods

EVIDEM framework source

Expert panel design and duty

Literature review and evidence matrix

Data analysis

Results

Weights of 13 criteria

Scores based on the evidence matrix

Need for intervention domain

Comparative outcomes of intervention domain

Type of benefit of intervention domain

Economic consequences of intervention domain

Knowledge about intervention domain

Estimated value contribution of VPZ and TPZ

Discussion

Conclusion

Declarations

References

Additional Declarations

Supplementary Files

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