This was randomised control open label study on 80 patients at Medicine OPD/IPD of tertiary care hospital. Sample size was based on prevalence rate of GERD in India (7.6%) [10]. It was calculated based on the following formula 4 pq/n²

(p=prevalence of GERD in India=7.6%, q=100-p, n=error (6% in our study)

Sample Size=4×7.6×(100-7.6)/62

=78.2

The study was started after getting approval from institutional Ethics committee (Ref SKNMC/Ethics/App/2016/142). Patients were screened by convenient sampling method. Drug allotment was done by simple randomisation method.

Inclusion criteria were: age ≥18 years and <70 years, the presence of any gastrointestinal symptoms like heartburn (burning sensation in the chest accompanied by pain) and/or regurgitation (acid taste and bitter to the tongue), diagnosis of initial clinical or previous symptomatic GERD with FSSG Symptom score ≥8 and no history of taking any antisecretory drugs, antacids and prokinetics for at least 14 days.

Exclusion criteria were: presence of oesophagitis requiring intervention, oesophageal varices, Barrett’s oesophagus, scleroderma, ulcers (gastric or duodenal), atrophic gastritis, eradication treatment of H. pylori completed less than 15 days of starting treatment, Gastric or oesophageal surgery, gastric surgery, or upper gastrointestinal diseases such as gastric cancer or peptic ulcer; females in pregnancy, lactation, or who wish to become pregnant if they refuse to use adequate contraception during the study period and concomitant serious diseases such as kidney failure, heart and liver failure; use of other scheduled medications metabolised by cytochrome CYP3A4 during the study like benzodiazepines, warfarin and phenytoin.

After taking a written informed consent, patients were allotted randomly into following two groups: One group was given Tab. PanD that is Pantoprazole (40 mg)+Domperidone (30 mg) once daily for two weeks, while another group was only given Tab Pan 40 that is Pantoprazole (40 mg) once daily for two weeks. Both the drugs are from Alkem Company, procured and supplied by researcher to patients [Table/Fig-1].

[Table/Fig-1]:

Consort flow chart.

The FSSG questionnaire [7,8] was administered pre-treatment and after treatment at two weeks. FSSG results were considered in terms of total score, reflux score, and dyspeptic score (maximum; TS 48, RS 28, DS 20 points, respectively). Total score was considered to carry out the pharmacoeconomic analysis.

Following parameters were used to evaluate cost effectiveness [11]:

The characteristics of all treatment groups were compared for both demographic and efficacy variables (FSSG score). All the data was recorded in the entry form and presented as mean±SEM/SD for numerical data, and proportion (%) for the categorical data. In all tests mean values of pre and post score compared with Student’s paired t-test. Difference between improvement of FSSG score of Pan and PanD group compared with unpaired t-test significance. Data was analysed using graph pad prism software version 6. The p<0.05 was considered as significant.

Out of 80 patients enrolled in this study, most patients were in age group 19-38 with male predominance. Symptoms are more common in patients with mix diet. Average FSSG total prescore is 15.23 with Pan and 18.45 with PanD [Table/Fig-2].

After treatment for a period of two weeks there is statistically highly significant change observed in all types of FSSG score in both groups [Table/Fig-3].

Comparison of individual improvement scores (difference in pre and post score) between Pan and PanD groups showed no statistically significant difference although PanD group has higher improvement score compared to Pan group [Table/Fig-4].

It was found out that for having the same unit improvement 9.7 Rs are required for Pan and 11.2 Rs required for PanD. Thus Pan is more cost effective than PanD [Table/Fig-5].

There is difference between prices of Pan and PanD. Moreover, for each of these drugs, there is also a vast difference in prices at hospital pharmacy (Generic by Archies life sciences) and at retailer (MRP of same drug, branded by the same company). Price of Branded drugs is four to five times more than their generic counterpart [Table/Fig-6]. Few adverse effects were observed with both the drugs during study period [Table/Fig-7].

In this prospective study a total of 80 patients were included. Most patients studied in this study were in age group 19-38 with male predominance as seen in [Table/Fig-2]. The FSSG score analysis was done where in the reflux, dysmotility and total scores for Pan and PanD before and after treatment were compared. As expected, total scores for both Pan and PanD decreased significantly. Total score of Pan decreased from 15.23 to 3.91 and for PanD decreased from 18.45 to 5.52 and the values are statistically significant as seen in [Table/Fig-3].

Few studies are available with combination of pantoprazole plus mosapride, omeprazole plus cisapride, omeprazole plus domperidone as seen in [Table/Fig-8] [2,4,12-19]. In these studies additional benefit of prokinetics to a standard dose of PPI in patients with GERD, was seen mostly in the subgroup of severely symptomatic patients [3,4,13,15,20]. Probable reason for this beneficial action is the combination of PPI and prokinetics acting synergistically by decreasing acid production as well as improvement of lower oesophageal sphincter function, improvement of oesophageal motility, and acceleration of gastric emptying, thus producing a better therapeutic response [21].

PPIs with prokinetics combination also improve the effect of PPIs. PPIs are unstable at a low pH, further dysmotility will slow down gastric emptying, resulting in retention of PPIs. Retention of PPIs inside the stomach for a long time may result in an impaired acid suppressive effect, so rapid transit of the PPIs to the upper intestine may be of benefit [8]. So, even this combination can be used in patients with GERD even without symptoms of dysmotility.

But in current study when we compared the individual improvement scores between Pan and PanD the results were not statistically significant as seen in [Table/Fig-4]. Pantoprazole is the more acid stable PPI [22]. Add on action of Domperidone that is increased gastric emptying and rapid transit of PPI to the upper intestine might not have helped with Pantoprazole. Thus, instead of Pantoprazole combination of other acid unstable PPI like omeprazole and prokinetc agents may have better efficacy than PPI alone as seen in some previous studies [2]. Current findings were in accordance with meta-analysis conducted by Ren L-H et al., where he concluded that there is no advantage for the addition of prokinetics to a PPI therapeutic regimen, relative to PPI alone [6]. However, combined therapy of PPI plus prokinetic may partially improve patient’s quality of life, but has no significant effect on symptom or endoscopic response of GERD.

There are many preparations in the market of about 120 for Pantoprazole in price range of 18-80 rupees and for 131 for PanD in range of 55 to 117 rupees [23,24]. Thus, due to wide price ranges, cost effective ratio is very important having impact on budget.

The ACER (Average Cost Effectiveness Ratio) was calculated by dividing the cost of treatment by its clinical outcome (FSSG score). Thus Pan is more cost effective than PanD.

On doing the cost minimisation analysis where only cost and not the efficacy were considered, the costs included in our study were Rs 79 for 10 tablets of Pan and 105 Rs for PanD. Thus Pan is cheaper than PanD. Other notable observation was that generic brands of both drugs (procured from Hospital pharmacy that is non Branded Generic) are cheaper than branded drugs (available at medical store and sell at MRP). Therapeutic switching to an equivalent cheaper or generic PPI would reduce financial burden on the patients without affecting the quality of patient care. Other studies in India have shown a very significant difference of prices between branded and generic drugs. The cost of branded drugs prescribed was 20% to 21.8% more than the generic versions [25,26]. There is need to start more no of generic stores or Janaushadhi stores programme initiated by Government of India.

We observed few adverse drug reactions in present study where two patients had headache, one had nausea in Pan group and one each had diarrhoea for Pan and PanD as seen in [Table/Fig-6]. Other studies also reported few adverse effects with PPI and Prokinetics [6,27]. This may be the reason for giving these drugs for long time and with good patient compliance.

Limitation of our study was that follow-up was not done and recurrence was not seen which commonly occurs in patients with acid peptic disease after stopping treatment. It was not feasible to co-relate FSSG score with Endoscopic finding as endoscopy was not advised to these patients. Pharmmacoeconomic analysis should be done with using different brands.

Pantoprazole is most commonly available PPI with 120 brands with price range Rs18-80 cheaper than PanD. There is vast difference between Branded and Generic drugs. Both drugs provide the most effective control of gastric acidity and related symptoms. PAN is more cost effective than PanD. PanD should be preferred only for PPI resistant GERD, patients with nausea and vomiting, in the subgroup of severely symptomatic patients.