Impact of PPIs on patient focused symptomatology in GERD

Figures & data

Table 1 Main characteristics of the identified evaluative symptom scales

Name	GERD-specific	Multidimensional	Self-assessed	Daily assessed	Available in different languages	Psychometrically validated
GERD Score	✓	–	–	–	–	✓
UESS	–	✓	✓	–	–	✓
GSAS	✓	✓	✓	–	–	✓
GSRS	–	–	✓	–	✓	✓
GRACI	✓	–	(✓)*	(✓)*	–	–

Abbreviations: GERD, gastroesophageal reflux disease; GRACI, GERD Activity Index; GSAS, GERD Symptom Assessment Scale; GSRS, Gastrointestinal Symptoms Rating Scale; UESS, Ulcer Esophagitis Subjective Symptoms Scale.

* Only parts of the scale.

Table 2 Recommendations for an ideal GERD symptom assessment instrument suitable as a primary end-point for clinical trials

be sensitive in patients with GERD cover the frequency and intensity of typical and atypical GERD symptoms be multi-dimensional (cover all symptom dimensions) have proven psychometric properties (validity, reliability, and responsiveness) be practical and economic be self-assessed (self-administered) use “word pictures” which are easy to understand for patients respond rapidly to changes (responsiveness over short time intervals) be used daily to assess changes during and after therapy be valid in different languages for international use

Adapted with permission from Bardhan KD, Berghofer P. 2007. Look – but also listen! ReQuest^™: An essay on a new validated scale to assess the outcome of GERD treatment. Digestion, 75(Suppl):87–100. Copyright © 2007 S. Karger AG.

Table 3 ReQuest™: Validation (statistical results)

Statistical test	What the test assesses	Range of results	Results: Threshold that needs to be exceeded or matched	Results obtained
				erosive esophagitis	non erosive reflux
Cronbach’s alpha	Internal consistency	0 to 1	>0.70	0.90	0.91
Intra-class correlation coefficient	Test-retest reliability*	0 to 1	>0.70	LQ 0.94 SQ 0.86	LQ 0.89 SQ 0.78
Construct validity	Correlation of prototype against existing instruments	−1 to 1	Approximately ± 0.5	GSRS 0.52 PGWB −0.48 (Spearman coefficient)	GSRS 0.55 PGWB −0.39 (Pearson coefficient)
Responsiveness index	Quantifies the ability to measure GERD symptom changes as a result of treatment	0 to infinity	>0.80	165	320

Abbreviations: *Reproducibility of the LQ & SQ is tested: LQ vs LQ, LQ vs SQ, SQ vs LQ, SQ vs SQ, LQ, Long questionnaire; SQ, short questionnaire; GSRS, gastrointestinal symptom rating scale; PGWB, pshchological general well being index scale. Reproduced with permission from Bardhan KD, Berghofer P. 2007. Look – but also listen! ReQuest^™: An essay on a new validated scale to assess the outcome of GERD treatment. Digestion, 75 (Suppl): 87–100. Copyright © 2007 S. Karger AG.

Figure 1 Changes in gastro-oesophageal reflux disease (GORD) related symptoms as assessed by ReQuest^™ in an intention to treat population of 421 patients with GORD during treatment with pantoprazole 20 mg/day (Los Angeles [LA] Grade A) or 40 mg/day (LA grades B-D). Reproduced with permission from Bardhan KD, Stanghellini V, Armstrong D, et al. 2004a. Evaluation of GERD symptoms during therapy. Part I. Development of the new GERD questionnaire ReQuest. Digestion, 69:229–37. Copyright © 2004 S. Karger AG.

Table 4 Complete remission, endoscopically confirmed healing and symptom relief rates (%) after 4, 8, and 12 weeks

Treatment	Duration of treatment
	4 weeks		8 weeks		12 weeks
	ITT	PP	ITT	PP	ITT	PP
Complete remission
Pantoprazole	47	59	69	86	76†	93†
Esomeprazole	49	62	70	84	76†	90†
CI	[−10.4,+∞]	[−12.2, +∞]	[−8.0, +∞]	[−4.6, +∞]	[−7.0, +∞]	[−2.9, +∞]
Endoscopically confirmed healing
Pantoprazole	69	75	86	94	91	98*
Esomeprazole	69	75	83	90	98	94*
CI	[−7.39, 7.69]	[−8.08, 8.55]	[−3.01, 8.68]	[−0.80, 9.59]	[−1.75, 9.59]	[0.02, 7.27]
System relief
Pantoprazole	63	76	77	90	79	95
Esomeprazole	64	78	75	89	77	92
CI	[−8.8, 6.9]	[−10.2, 6.0]	[−5.3, 8.6]	[−4.9, 6.8]	[−4.7, 8.8]	[−1.8, 7.9]

Abbreviations: ITT, intention to treat; PP, per-protocol; CI, confidence interval of the difference.

* superiority of pantoprazole (CI above 0);

^† primary outcome criterion. Reproduced with permission from Bardhan KD, Achim A, Riddermann T et al 2007. A clinical trial comparing pantoprazole and esomeprazole to explore the concept of achieving ‘complete remission’ in gastro-oesophageal reflux disease. Aliment Pharmacol Ther, 25:1461–69. Copyright © 2007 Blackwell Publishing Ltd.

Table 5 Symptom pattern in patients with different endoscopic GERD grades given as mean total score values dimension load

Dimension of ReQuest^™	Grade A (n = 182)	Grade B (n = 130)	Grade C (n = 33)	Grade D (n = 4)
Acid complaints	85.2*	82.3	81.8	100
Upper abdominal/stomach complaints	75.8	73.9	75.8	75.0
Lower abdominal/digestive complaints	57.1	47.7	57.6	75.0
Nausea	37.9	38.5	39.4	50.0
Sleep disturbances	65.4	59.2	60.6	100
Other complaints	61.0	63.9	57.6	75.0

* Mean total score values, dimension load = frequency times intensity per protected, 349 patients at baseline. After Heading et al 2006.

Table 6 Complete remission rates (%) after 4, 8, and 12 weeks (per protocol population)

Patient group	4 weeks	8 weeks	12 weeks
NERD	64	83	90
Grade A esophagitis	62	81	88
Grade B esophagitis	43	66	83
Grades C/D esophagitis	32	64	78

After Heading et al 2006.

Table 7 Endpoints of symptom relief or healing at 4, 8, or 12 weeks

Rates	4	8	12
Symptom relief	77	90	93
Healing rates	75	92	96
Complete healing	61	85	81

After Heading et al 2006.

Table 8 Mean pre-post differences between baseline and after 28 days of treatment

	Panto 40 mg	Eso 40 mg	Δ %	p-value
	Mean score (SD)	Mean score (SDa)
Acid dimension	−2.32 (± 2.01)	−2.12 (± 2.12)	9	<0.0001
ReQuest^™-GI	−5.33 (± 5.38)	−4.44 (± 4.97)	17	<0.0001

After Thomson and Peter 2007.

^a Standard deviation.

Table 9 Mean acid dimension pre-post differences for GERD grades at baseline and after 28 days of the treatment

LA Grade	Panto 40 mg	Eso 40 mg	Δ %	p-value
	Mean score (SDa)	Mean score
A	−1.97 (± 1.94)	−1.78 (± 1.90)	10	0.046
B	−2.49 (± 2.02)	−1.87 (± 1.90)	25	<0.0001
C/D	−2.43 (± 2.03)	−2.05 (± 2.03)	16	0.025

After Thomson and Peter 2007.

^a Standard deviation.

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