sonika final report intas (1)

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A SUMMER TRAINING PROJECT REPORT

INDEX

SR. NO.

TOPIC PAGE NO.

1. INTRODUCTION 2-3

2. OBJECTIVE 3

3. SIGNIFICANCE 3-4

4. DATA COLLECTION 4-6

5. RESEARCH METHODOLOGY 6-8

6. DATA ANALYSIS 9-23

7. LIMITATION 23

8. DISCUSSION 24-25

9. BIBLIOGRAPHY 26

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INTRODUCTION

Schizophrenia is a psychotic disorder marked by severely impaired thinking, emotions, and behaviours. Schizophrenic patients are typically unable to filter sensory stimuli and may have enhanced perceptions of sounds, colours, and other features of their environment. Most schizophrenics, if untreated, gradually withdraw from interactions with other people, and lose their ability to take care of personal needs and grooming.

The course of schizophrenia in adults can be divided into three phases or stages. In the acute phase, the patient has an overt loss of contact with reality (psychotic episode) that requires intervention and treatment. In the second or stabilization phase, the initial psychotic symptoms have been brought under control but the patient is at risk for relapse if treatment is interrupted. In the third or maintenance phase, the patient is relatively stable and can be kept indefinitely on antipsychotic medications. Even in the maintenance phase, however, relapses are not unusual and patients do not always return to full functioning.

Typical antipsychotic (sometimes referred to as first generation antipsychotics, conventional antipsychotics, classical neuroleptics, or major tranquilizers )which include drugs like Chlorpromazine,Droperidol,Flupenthixol,Fluphenazine,Haloperidol,Thioridazine act on the dopaminergic system, blocking the dopamine type 2 (D2) receptors. Atypical antipsychotics (also known as second generation antipsychotics) such as Clozapine,Olanzapine,Risperidone have lower affinity and occupancy for the dopaminergic receptors, and a high degree of occupancy of the serotoninergic receptors 5-HT2A.

Typical antipsychotics use may consequently increase the risk of a wide variety of undesirable side-effects. For example, their anticholinergic side-effects include dry mouth, urinary hesitancy, constipation and visual disturbance.Furthermore, their prolonged use may lead to weight gain. Interference with dopaminergic transmission can lead to both endocrinological side-effects such as hyperprolactinaemia, which may manifest itself as galactorrhoea, amenorrhoea and gynaecomastia, and extrapyramidal side-effects (EPS).

Atypical antipsychotics have gained much notoriety for causing metabolic derangements including weight gain, dyslipidemia, and hyperglycemia including new-onset type 2 diabetes mellitus (T2DM). These adverse effects are all risk factors for cardiovascular disease, and along with lifestyle and genetic components, contribute to the decreased lifespan of patients with schizophrenia.

Olanzapine is a most commonly used drug in schizophrenia that faces a problem of weight gain.Which have been tried to overcome by the use of Olimelt which is a mouth dissolving tablet (ODT) and have shown lesser weight gain as compare to standard olanzapine tablet(SOT) according to the clinical survey.

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In a non-randomized, observational clinical study by (Czekalla 2007) shows comparable outcomes and tolerability in patients treated with both olanzapine formulations. In an acute treatment setting, orally disintegrating tablets were preferably used for more severely ill and aggressive patients with low medication acceptance. In this study the rating of medication acceptance shows that ODT is preferably given to patients with a negative attitude towards medication and who are, therefore, at risk of being non-compliant, but still can be persuaded to accept oral medication.

OBJECTIVE

The objective of the present survey is to develop national baseline estimates and determine the extent of olimelt(ODT) prefer by the doctors.

Olanzapine comes in the form of standard tablets in market and also come in oral disintegrating formulation. So the issue is to check the effectiveness and medication acceptance of olanzapine disintegrating tablets compares to standard olenzapine tablets in patients.

olanzapine is an effective second-generation antipsychotic (1,2). However,weight gain has been very commonly observed during olanzapine treatment and this may increase the risk of treatment non-adherence and relapse and exacerbate poor self-esteem and the risk of comorbidities (3,4). Consequently, there is an important need to develop effective strategies to prevent, minimise or reverse weight gain during treatment with olanzapine.

The potential option for minimising weight gain during olanzapine therapy is to switch patients from the standard olanzapine tablets (SOT) formulation of olanzapine to orally disintegrating olanzapine (ODO) tablets.

The another objective of this study is to obtain patient compliance as Patients ’ preference is both clinically and financially important, and it can have a long-term implications in terms of patients ’ motivation and insight into their disease state and its treatment, which might have a direct impact on the patient’s compliance and treatment adherence.

SIGNIFICANCE

Significance to traineeThrough this work we came to know about new formulation of olanzapine molecule that is ODT OLIMELT besides its conventional formulation that is already available. We also become aware of the limitation of the conventional formulation and options to overcome it.

This project throws light on us about the market surveillance as per company’s prospective. We knew about the parameters which are taken into consideration during market survey.

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By doing this work we had a chance to interact with company employees and the methodology which INTAS uses for carrying out market surveillance of any new formulation.

Significance to INTAS

Through this kind of study the company knows about the successful rate of the product that has been launched in market.

The company carries out this study to know how successfully the new formulation overcomes the limitation of the conventional formulation.

The company carries out the survey in different zones of the country to know intersubject variability.Market survey can help the company to know about the doctors preference to the new formulation in place of conventional ones and the major reasons to shift to the new formulation.

The company’s profit also taken in to consideration in carrying out this kind of studies.

Significance to subject

Violence is a complex behavioral phenomenon with many causes. Violence and aggressive behavior are common among patients with psychiatric disorders so they are commonly refuse to take drug, this problem can be overcome by the use of mouth dissolving olimelt. Since these patient deny to take the drug,ODT can be given with the patient’s food and drinks.

There are many ways to manage violent situations. One of them by using antipsychotic agent like olanzapine. Olanzapine is second-generation antipsychotic agents, and it has more than 1 route of delivery such as oral ,intramuscular etc. Orally disintegrating olanzapine tablets (olanzapine ODT) produced similar improvements in acutely agitated patients.

DATA COLLECTION

‘ASTERA’ A Division of INTAS Pharmaceutical Pvt. Has collected data of one survey project for revealing the ‘doctors perception’ for the OLIMELT that is ODT formulation of the olanzepine molecule.

INTAS has collected these data from the conferences which were organized by the company at where the doctors were made to fill this survey card.

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The other way to collect this data by the help of medical representative whom visit the doctors for the product marketing.

We procure these data from INTAS PHARMACEUTICALS which was collected from different zones of country.

The picture shows the survey card designed by INTAS which was made to fill by the doctors to give their opinion about the olimelt.

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There are seven question mentioned in this survey card but mainly four questions that is question no. 4,5,6,7 were analysed.

Question no 4 is about the experience of less weight gain with olimelt which is one of the major side effect with SOT formulation.

Question no 5 mentions about the average no. of new and old schizophrenic patients that doctors diagnosed daily.

Question no 6 is about the percentage break up of the neuroleptics preferred by the doctors in newly diagnosed schizophrenic patients.

Question no 7 is about the major reason as well as the percentage shift for the other neuroleptics.

RESEARCH METHODOLOGY

As per the data provided by the INTAS PHARMACEUTICALS based on the survey regarding OLIMELT (ODT) and its preference by the doctors over the SOT, A series of the statistical and mathematical tool were applied for analysing and compiling the data.SPSS a software of statistical analysis is used for carrying out various statistics test such as t-test, chi-square test, correlation coefficient, regression ANOVA etc and various graphical presentations like pie chart, bar graph are used to analyse these collected data.

THE CHI-SQUARE TEST

Introduction: The chi-square test is a statistical test that can be used to determine whether observed frequencies are significantly different from expected frequencies. we would use a chi-square test to compare the observed and expected frequencies and determine whether there is a statistically significant difference between the two. As in other statistical tests, we begin by stating a null hypothesis (H0: there is no significant difference between observed and expected frequencies) and an alternative hypothesis (H1: there is a significant difference). Based on the outcome of the chi-square test we will either reject or fail to reject the null hypothesis.

Importance: Chi-square tests enable us to compare observed and expected frequencies objectively, since it is not always possible to tell just by looking at them whether they are "different enough" to be considered statistically significant. Statistical significance in this case implies that the differences are not due to chance alone, but instead may be indicative of other processes at work.

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Purpose of Chi Square:

The Chi Square (X2) test is undoubtedly the most important and most used member of the nonparametric family of statistical tests. Chi Square is employed to test the difference between an actual sample and another hypothetical or previously established distribution such as that which may be expected due to chance or probability. Chi Square can also be used to test differences between two or more actual samples.

Basic Computational Equation

Example:

Interpretation of chi-square

o The magnitude of the chi-square value must be judged against a table of values of the chi-square distribution:

o One must enter this table using the appropriate degrees of freedom: calculated according to the size of the table:

o X2 degrees of freedom = df = (rows - 1) (columns - 1)

o Given the same degrees of freedom, the larger the chi-square value, the more "significant" it is.

o The entries in the chi-square table for a given chi-square are matched with "alpha" levels at specified levels of significance, e.g., .050 or .010 or .001

o A chi-square as large as 75 for 10 degrees of freedom would be expected by chance fewer than 1 time in 1000.

BAR CHART OR BAR GRAPH

A bar graph is that two dimensional graphic representation where the elementary graphic objects are a set of rectangles drawn in parallel so that the extension of the same is proportional to the magnitude they intend to represent.

The rectangles, or bars, can be either horizontally or vertically positioned. In the latter case they receive the name ofcolumn graphs or charts.

In the following we'll refer to both of them as "bar graphs" independently of the orientation of the rectangles.

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Typically they are used to compare magnitudes among several categories or the evolution in time (the change) of a particular magnitude. the comparison of the evolution in time of several categories, i.e., they are also used

as a blend of the two preceding uses.

PIE CHART

A pie chart is a graphical data analysis technique for summarizing the distributional information of a variable. It is a circular plot consisting of wedges where the size of each wedge is proportional to the frequency (= number of observations) in that wedge. The plot is to be read clockwise.

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DATA ANALYSIS

ANALYSIS OF QUESTION NO.4

We analysed the data for less weight gain experience of the patient with olimelt by using chi-square test with the help of SPSS software. HYPOTHESIS

H0 = Patient not experience less weight gain HA = Patient experience less weight gain

OUTPUT

WEIGHT BY exp.witholimeltt .NPAR TEST /CHISQUARE=exp.witholimeltt /EXPECTED=EQUAL /STATISTICS DESCRIPTIVES /MISSING ANALYSIS.

Descriptive Statistics

N Mean Std. Deviation Minimum Maximumexperience of less weight gain with olimelt 433 1.43 .496 1 2

Chi-Square Test

Frequencies

experience of less weight gain with olimelt

Observed N Expected N ResidualYes 245 216.5 28.5No 188 216.5 -28.5Total 433

Test Statistics

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experience of less weight gain with olimelt

Chi-Square(a) 7.503

Df 1Asymp. Sig. .006

a 0 cells (.0%) have expected frequencies less than 5. The minimum expected cell frequency is 216.5.

RESULT

The chi-square value obtained by using SPSS software is 7.503 which is much greater than 3.84(table value of chi-square) at 5% level of significance with degree of freedom 1. As per the rule the value at the right side of 3.84 is the rejection area while at the left side it is the acceptance region. Since our result value is 7.503 which on the right side of the graph, the null hypothesis is rejected and alternative hypothesis is accepted.The value 7.503 is much greater then 3.84(table value) so we can say that the value is highly significant.

CONCLUSION

From the above result it can be concluded that olimelt has been successful in overcoming the limitation of weight gain which was experience by the SOD.

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ANALYSIS FOR QUESTION NO.5

The sample size of the patient seen by a doctor per day was determined by finding the average of new and old patient and plotting a chart for finding the ratio of old vs new schizophrenic patient seen by a doctor per day.

OUTPUT

SD 0.577350269

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RESULT

The bar graph is used to analyze the data of schizophrenic patient that the doctor diagnosis daily. The graph is plotted for average no. of schizophrenic patient diagnosed by a doctor per day.The average value of new schizophrenic patient is 3.60 and that for old patient is 9.86. The standard deviation obtained for the new patient is 0.577350269 and that for old patient is 0.707106781.

CONCLUSION

From the above graph it can be concluded that doctors come across more to the old schizophrenic patient than new patient daily.

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ANALYSIS OF QUESTION NO.6

The percentage break up of the neuroleptics preffered by the doctors in newely diagnosed schizophrenic patients is calculated by finding the percentage of each of the drug and plotted in a pie-chart.

OUTPUT

The pie chart is used to know the doctors preference for the antipsychotic drugs in case of newly diagnosed schizophrenic patient. The antipsychotic agents used by the doctors are olanzapine, haloperidol, risperidone, quetiapine, amisulpride, aripirazole, ziprasidone and others.

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RESULT

The average percentage of olanzapine used is 55.88. Doctors prefer this drug in case of symptoms like insomnia, aggression, irritability and positive symptoms.

The average percentage of haloperidol is 15.91. It is preferred in the symptoms like aggression, acute cases and positive symptoms.

The average percentage of risperidone is 20.86. it is preferred in the symptoms like aggression,insomnia, positive symptoms and persistent symptoms.

The average percentage of quetiapine is 8.91. It is preferred in the symptoms like aggression,insomnia and negative symptoms. It is mainly used for the young patient.

The average percentage of amisulpride is 7.64, Aripirazole is 3.00 Ziprasidone is 0.587And others is 1.722.

CONCLUSION

From the above graph it can be concluded that olanzapine is the most widely used drug by the doctor in case of newly diagnosed patient. Other than this haloperidol and risperidone is also preferred by the doctor.

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ANALYSIS OF QUESTION NO. 7

For determine the shifting of various typical and atypical neuroleptics which are mentioned in survey given a code and then according to their percentage shift it was representated by plotting a pie chart and bar graph.

WEST ZONE OF INDIA

SHIFTING OF ONE NEUROLEPTICS TO OTHERS

category percentage.prefferenceolanzapine 55haloperidol 3risperidone 11quetiapine 8amisulpride 9aripiprazole 7ziprasidone 2others 5

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The above pie chart indicates the maximum shift occurs in olanzapine.

The order of shift of various neuroleptics is in following manner.

OLANZAPINE>RISPERIDONE> AMISULPRIDE>QUETIAPINE> ARIPIPRAZOLE>OTHER NEUROLEPTICS>HALOPERIDOL>ZIPRASIDONE

Shifting of other neuroleptics to olanzapine

category no.of shiftshaloperidol-olanzapine 37risperidone-olanzapine 11amisulpride-olanzapine 2others-olanzapine 5

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The shifting to olanzapine from previous neuroleptic occurs in the following order haloperidol > risperidone >others>amisulpride

Shifting to haloperidol

category no.of shiftsolanzapine - haloperidol 3

Out of data obtained from 100 doctors, only 3 doctors shift to haloperidol from the previous neuroleptic.

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Shiftng to risperidone

Category no.of shiftsolanzapine-risperidone 4haloperidol-risperidone 3others-risperidone 4

Out of 100 doctors opinion, only 11 doctors prefer to shift to risperidone from olanzapine, haloperidol and others.

Shifting to quetiapine

category no.of shiftsolanzapine-quetiapine 6haloperidol-quetiapine 2

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The total shift to quetiapine was found to be 8. Out of which 6 shifts were from olanzapine and 2 shifts were from haloperidol.

Shifting to amisulpride

category no.of shiftsolanzapine-amisulpride 9

According to the 100 doctors opinion, only 9 doctors prefer to shift to risperidone from olanzapine only.

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Shifting to aripirazole

category no.of shiftsolanzapine-aripirazole 6amisulpride-aripirazole 1

Total shift to aripiprazole was found to be 7 from olanzapine and amisulpride.

Shifting to ziprasidone

category no.of shiftsolanzapine-ziprasidone 1risperidone-ziprasidone 1

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According to the doctors view only 2 shifts to the ziprasidone were observed.one from olanzapine and other from risperidone.

Shifting to other neuroleptics

category no.of shiftsolanzapine-others 2risperidone-others 2

Out of 100 doctors only 4 doctors preferred other neuroleptics and the shift was from olanzapine and risperidone.

EAST ZONE OF INDIA

SHIFTING OF ONE NEUROLEPTICS TO OTHERS

category percentage.prefferenceolanzapine 62.5haloperidol 6.25risperidone 6.25amisulpride 12.5aripiprazole 6.25others 6.25

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Shifting of other neuroleptics to olanzapine

category no.of shiftshaloperidol-olanzapine 8risperidone-olanzapine 1others-olanzapine 1

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RESULT

The data obtained from the west zone is quite sufficient for the analysis than data obtained from the east zone of India. With the use of pie chart we have analysed the percentage shifting in the neuroleptic agents.It was observed by analysing the survey card that the major reasons for the shift from haloperidol to olanzapine are extra pyramidal side effects, galactorrhea, insomnia.The reason for the shift of olanzapine to resperidone is weight gain and sedation.For the diabetic patient doctors preferred quatiapine in place of olanzapine.

CONCLUSION

From the above analysis it can be concluded that the major shifting is to the olanzapine drug in both east and west region of the country.

LIMITATION

Since the data were procured by the company itself so we did not have a chance to interact with the doctors and knew their strategy. Due to this we could not have more information other than those described in the survey card.

There was lack of support from the doctors as they did not give the information up to the point. Many columns like symptoms, reasons for shifting etc were left blank by the doctors.

There were no numerical data available for the patient experience of less weight gain since it was a close ended question in the survey card.

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DISCUSSION

After analysing the survey card of east and west region of India it was reported that olanzapine is most preferable drug in india and olimelt which is a ODT formulation of olanzapine shows less weight gain as compare to SOT formulation and it was proved statistically also. Some clinical trials give evidence, for example A study is being done to compare the changes in weight (kg) and body mass index (BMI) (kg/m(2)) in 52 hospitalized adolescents between baseline and after 12 weeks of monotherapy with either (i) olanzapine (OLZ) orally disintegrating tablets (ODT) , (ii) OLZ standard oral tablets , or (iii) risperidone . Significantly greater increases in mean weight and BMI were observed in the patients treated with OLZ SOT than in those with ODT . These findings suggest that adolescents gain less weight with OLZ ODT than OLZ SOT (Crocq MA et al.2007)

Reason for Possible less weight gain when patients switch to orally disintegrating olanzapine from oral olanzapine tablets is observed in following studyDifference in absorption between olanzapine orally disintegrating tablets (ODT) and olanzapine standard oral tablets (SOT) is suggested to be important regarding this matter. Partial sublingual absorption occurring with orally disintegrating olanzapine may bypass gastrointestinal metabolisation and hence lead to differences in metabolite versus parent compound ratios (Arranz et al. 2007).

By analysing 295 doctors daily schedule to find the number of new and old patient seen by a doctor per day. It was observed that doctors come across more to the old schizophrenic patient with compare to new patient daily.

Neuroleptics(Olanzapine,haloperidol,risperidone,quetiapine,amisulpride,aripiprazole,ziprasidone others )which are mentioned in survey card, olazapine is the most preferable neroleptic and ziprasidone is the least preferable. The order of preference of these neuroleptics which has been analysed from the survey cards is in the following way.

Olanzapine>risperidone>haloperidol>quetiapine>amisulpride>

aripiprazole> others >ziprasidone.

This has been observed that Olanzapine is the most preferable drug in east and west region of India and according to the doctors this is more promising nueroleptics as compare to othersSo this must be the reason for major shifting to Olanzapine.

Due to insufficient data of east region we are not able to produce actual reports but major shift to Olanzapine is observed clearly

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In the west region The majority of the shift from various neuroleptics is to olanzapinewhich account for about 55% in a survey of the doctors.

In the west zone the shift was in following manner:

OLANZAPINE>RISPERIDONE>AMISULPRIDE>QUETIAPINE>ARIPIPRAZOLE>OTHER NEUROLEPTICS>HALOPERIDOL>ZIPRASIDONE

The shift to olanzapine has mostly occurred from haloperidol, risperidone, quetiapine, amisupride and from other neuroleptics.

Shifting from these neuroleptics to the Olanzapine is being done because these neuroleptics have several side effects like extra pyramidal side effects, galactorrhea, insomnia.

Some doctors also report the shift from olanzapine to other neuroleptic due to weight gain and sedative effects of olanzapine. For the diabetic patient doctors preferred quatiapine in place of olanzapine .

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BIBLIOGRAPHY

www.medscape.com/viewarticle/733704

www.statpac.com/statistics-calculator/counts.htm

Littrell KH, Petty RG, Wolf NM. Olanzapine: a 5-year perspective.

Expert Rev Neurother 2006; 6: 811–21.

Leucht S, Corves C, Arbter D et al. Second-generation versus

firstgeneration antipsychotic drugs for schizophrenia: a meta-analysis.

Lancet 2009; 373: 31–41.

Crocq MA, Guillon MS, Bailey PE & Provost D: Orally disintegratin

olanzapine induces less weight gain in adolescents than standard oral

tablets. Eur Psychiatry. 2007; 22:453-4.

Arranz B, San L, Dueñas RM, Centeno M, Ramirez N, Salavert J & Del

Moral E: Lower weight gain with the orally disintegrating olanzapine

than with standard tablets in first-episode never treated psychotic

patients. Hum Psychopharmacol. 2007; 22:11-5.

http://www.ncbi.nlm.nih.gov/pubmed/17761403?ordinalpos=6&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum



http://www.statpac.com/statistics-calculator/counts.htm

http://www.medscape.com/viewarticle/733704

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