Rajive Gandhi University of Health Sciences, Karnataka, Bangalore

RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES, KARNATAKA, BANGALORE

ANNEXURE II

PROFORMA FOR REGISTRATION OF SUBJECTS FOR DISSERTATION

1. / Name of the candidate and Address (In block letters) / SAEED AKBARIAN
S/o Mahmoud
Marketing and Management Dept.
Al-Ameen College of Pharmacy
Hosur Road, Bangalore – 560 027
2. / Name of the Institute / AL-AMEEN COLLEGE OF PHARMACY
Hosur Road, Bangalore – 560 027
3. / Course of Study and Subject / M. PHARM
MARKETING AND MANAGEMENT
4. / Date of Admission to course / 9thJune 2009
5. / Title of the Topic
“Comparative market potential study between four drugs for treatmentof Osteoporosis in two Asian metropolitan cities of Bangalore and Tehran”
6. / Brief Resume of the Intended work
6.1Need for study
Osteoporosis is a term meaning ‘porous bone’. Osteoporosis is a disease in which the density and the quality of the bone are reduced, leading to weakness of the skeleton and increased risk of fractures, particularly of the spine, wrist and the hip. Osteoporosis associated fractures are an important cause of mortality and morbidity [1].
Approximately 1.6 million hip fractures occur each year worldwide, the incidence is set to increase to 6.3 million by 2050.Worldwide lifetime risk for osteoporotic fractures in women is 30-50%. In men risk is 15-30% [2].The worldwide cost burden of osteoporosis (for all ages) is forecast to increase to USD131.5 billion by 2050. Osteoporosis also results in huge indirect costs that are rarely calculated and which are probably at least 20%of the direct costs. Once a woman suffers a first vertebral fracture, there is a five-fold increase in the risk of developing a new fracture within one year [3].Osteoporosis continues to be an attractive therapy area for large pharmaceutical companies due to its high prevalence rate and unmet need. Globally, sales for osteoporosis drugs grew 7.0% year-on-year from 2004 to $9.6 billion in 2008 driven by strong performance of the bisphosphonate class [4].
Expert groups peg the number of osteoporosis patients at approximately 26 million with the numbers projected to increase to 36 million by 2013 in India.In a study among Indian women aged 30-60 years from low income groups, BMD at all the skeletal sites were much lower than values reported from developed countries, with a high prevalence of osteopenia (52%) and osteoporosis (29%) thought to be due to inadequate nutrition[1].The Osteoporosis segment in India currently has a market size of around Rs 219 crores and grew more than 29% in value terms in 2006-07 [5][6].
Iran accounted for 0.85% of the global burden of hip fracture and 12.4% of the burden of hip fracture in the Middle East [1].
There are various approaches for the management of osteoporosis. Those include:[10]

1. Life style changes includequitting smoking, curtailing alcohol intake, exercising regularly, and consuming a balanced diet with adequate calcium and vitamin D
2. Medications that stop bone loss and increase bone strength, such as alendronate, risedronate, raloxifene, ibandronate, calcitonin, and zoledronate, Strontium Ranelate
3. Medications that increase bone formation such as teriparatide (Forteo).

According to IMS Health, the U.S. selected Osteoporosis market share for different groups of products are as follow: (Prescription Sales Only)
Bisphosphonates 35.3%; Estrogens 32.8%; Estrogens/Progesterones 16.5%; Bone Den. Reg. (SERMs) 10.1%; Calcitonins 5.3%
Bisphosphonates are a group of drugs well known around the globe for treatment and prevention of osteoporosis. Several clinical trials have been done on these products making them even more popular for the osteoporosis therapeutic segment.
Considering the fact that Bisphosphonates are the first line products for preventing or treatment of osteoporosis and are also found to be most effective, these drugs are chosen for this study. Bisphosphonates under consideration of this project are:

1. Alendronate Sodium
2. Risedronate Sodium
3. Ibandronic acid Tablet

Strontium Ranelate is also selected because it is found to be a be a Dual Action product, since it not also increases bone mass but prevents absorption of bone as well.

1. Strontium Ranelate

Marketing research is the systematic design, collection and analysis and reporting of data and findings relevant to a specific marketing situation facing the company [9].
In market research a product’s performance will be monitored using measures such as product awareness, product preference, and product usage and how favorably customers view the product.
Due to the growth of aged population in all the countries and considering the fact thatgeriatrics are more prone to bone diseases, it is expected that this silent disease will involve more and more people in future, hence the importance of Osteoporosis therapeutic segment.
This project aims to do an evaluation of the market potential and its comparison for above mentioned prescription drugsfor the treatment/prevention of osteoporosis in two Asian markets, i.e., Iran and India.
Additional aspects the proposed study would cover are:

• The awareness of customers (physicians and specialists) of these products in the targeted market
• Which product in which market has a better potential and the factors indicating it?
• Is it price?Is it availability?Is it advertisements? Is it convenience in administration?
• Price is more important or convenience in administration for eachmarket?
• Which product physicians think is more effective?

The degree of acceptance of the identified molecules amongst clinicians will also be assessed /estimated. Ultimately the present study will uncover the most preferred parameters for an ideal drug for treatment/prevention of osteoporosis with respect to the different markets surveyed.
6.2Review of Literature
Osteoporosis is a condition characterized by the loss of the normal density of bone, resulting in fragile bone. Osteoporosis leads to literally abnormally porous bone that is more compressible like a sponge, than dense like a brick. This disorder of the skeleton weakens the bone causing an increase in the risk for breaking bones (bone fracture)[10].

Osteoporosis bone fractures are responsible for considerable pain, decreased quality of life, lost workdays, and disability. Up to 30% of patients suffering a hip fracture will require long term nursing home care. Elderly patients can further develop pneumonia and blood clots in the leg veins that can travel to the lungs (pulmonary embolism) due to prolonged bed rest after a hip fracture. Some 20% of women with a hip fracture will die in the subsequent year as an indirect result of the fracture. In addition, once a person has experienced a spine fracture due to osteoporosis, he or she is at very high risk of suffering another such fracture in the near future (next few years). About 20% of postmenopausal women who experience a vertebral fracture will suffer a new vertebral fracture of bone in the following year [10].

Osteoporosis is an important public health issue

One in two white women will experience a bone fracture due to osteoporosis in her lifetime.

• Globally, direct health care costs from osteoporosis fractures amount to billion dollars, without even taking into account the indirect costs, such as lost work productivity.
• Twenty percent of those who experience a hip fracture will die in the year following the fracture.
• One-third of hip fracture patients are discharged to a nursing home within the year after fracture.
• Only one-third of hip fracture patients regain their pre-fracture level of function.

With the aging of different countries of the world, the number of people with osteoporosis related fractures will increase exponentially. The pain, suffering, and economic costs will be enormous[10].
The goal of osteoporosis treatment is the prevention of bone fractures by stopping bone loss and by increasing bone density and strength. Although early detection and timely treatment of osteoporosis can substantially decrease the risk of future fracture, none of the available treatments for osteoporosis are complete cures. In other words, it is difficult to completely rebuild bone that has been weakened by osteoporosis. Therefore, prevention of osteoporosis is as important as treatment. Osteoporosis treatment and prevention measures are:

1. Life style changes
2. Medications that stop bone loss and increase bone strength
3. Medications that increase bone formation

Calcium Supplements

Building strong and healthy bones requires an adequate dietary intake of calcium and exercise beginning in childhood and adolescence for both sexes. Most importantly, however, a high dietary calcium intake or taking calcium supplements alone is not sufficient in treating osteoporosis, and should not be viewed as an alternative to or substituted for more potent prescription osteoporosis medications. In the first several years after menopause, rapid bone loss can occur even if calcium supplements are taken.

Vitamin D

An adequate calcium intake and adequate body stores of vitamin D are important foundations for maintaining bone density and strength. However, vitamin D and calcium alone are not sufficient treatment for osteoporosis. They are given in conjunction with other treatments.

Hormone therapy (menopausal hormone therapy)

Menopausal hormone therapy (previously referred to as hormone replacement therapy or HRT) has been shown to prevent bone loss, increase bone density, and prevent bone fractures. It is useful in preventing osteoporosis in postmenopausal women.
However, due to adverse effects of menopausal hormone therapy, such as increased risks of heart attack, stroke, blood clots in the veins, and breast cancer; menopausal hormone therapy is no longer recommended for long-term use in the therapy of osteoporosis. Rather, menopausal hormone therapy is used short-term to relieve menopausal hot flashes.

Medications that prevent bone loss and breakdown

Currently, the most effective medications for osteoporosis that are approved by the FDA are anti-resorptive agents, which prevent bone breakdown. The bone is a living dynamic structure; it is constantly being removed (resorbed) and rebuilt. This process is an essential part of maintaining the normal calcium level in the blood and serves to repair tiny cracks in the bones that occur with normal daily activity. Osteoporosis results over time when the rate of bone resorption exceeds that of bone rebuilding. Anti-resorptive medications inhibit bone removal (resorption), thus tipping the balance in favor of bone rebuilding and increasing bone density. Menopausal estrogen hormone therapy is one example of an anti-resorptive agent. Others include alendronate (Fosamax), risedronate (Actonel), raloxifene (Evista), ibandronate (Boniva), calcitonin (Calcimar), and the recently approved zoledronate (Reclast).
Alendronate
Alendronate is a biphosphonate anti-resorptive medication. Alendronate is approved for the prevention and treatment of postmenopausal osteoporosis as well as for osteoporosis that is caused by cortisone-related medications (glucocorticoid-induced osteoporosis). Alendronate has been shown to increase bone density and reduce fractures in the spine, hips, and arms. Alendronate is taken by mouth once-a-week to prevent and treat postmenopausal osteoporosis. Alendronate is the first osteoporosis medication also approved for increasing bone density in men with osteoporosis, either in a daily or a weekly dose schedule.
Alendronate is generally well tolerated with few side effects. One side effect of alendronate is irritation of the esophagus. Inflammation of the esophagus (esophagitis) and ulcers of the esophagus have been reported infrequently with alendronate use.
As with all potent bisphosphonates, the systemic bioavailability after oral dosing is low, averaging only 0.6–0.7% in women and in men under fasting conditions. Intake together with meals and beverages other than water further reduces the bioavailability. The absorbed drug rapidly partitions, with approximately 50% binding to the exposed bone surface; the remainder is excreted unchanged by the kidneys. Unlike most drugs, the strong negative charge on the two phosphate moieties limits oral bioavailability, and in turn, the exposure to tissues other than bone is very low. After absorption in the bone, alendronate has an estimated terminal half-life of 10 years [11].
Sr. No. / Brand Name / Company
1 / Fosamax Plus D Tablet® / Merck & Co Inc
2 / Fosamax Tablet® / Merck & Co Inc
3 / Alenost Tab / Macleod
4 / Bifosa Tab / Troikaa
5 / Benfos Tab / Dr. Reddy’s
6 / Dronal Tab / Orchid
7 / Osteofos / Cipla
8 / Ranelost-10 Tab / Ranbaxy
9 / Restofos Tab / Sun
Risedronate
Risedronate (Actonel) is another bisphosphonate anti-resorptive medication. Like alendronate, this drug it is approved for the prevention and treatment of postmenopausal osteoporosis as well as for osteoporosis that is caused by cortisone-related medications (glucocorticoid-induced osteoporosis). Risedronate is chemically different from alendronate and has less likelihood of causing esophagus irritation. Risedronate is also more potent in preventing the resorption of bone than alendronate. Its bioavailability is 0.63% and it protein binding capacity is found to be ~24%. It is not metabolized in the liver and half life for this drug is 1.5 hours. It is excretion is byrenal and fecal routes[11].Risedronate 35mg tablet administered once weekly is found to increase bone mass and used for treatment and prevention of Osteoporosis.
Sr. No. / Brand Name / Company
1 / Actonel Tab / Sanofi Aventis
2 / Fossical Tab / Medreich Saimirra
3 / Gemfos Tab / Alkem
4 / Risofos Film-Coated Tab / Cipla
Ibandronate
Ibandronate (Boniva) is an oral bisphosphonate for prevention and treatment of postmenopausal osteoporosis. It is available in both daily and monthly oral formulas as well as intravenously every three months.The product bioavailability is 0.6% only and bounded to proteins by 90-95%. It is not metabolized and its half life is 10 to 60 hours. It is excreted trough urine.[12] [13]. Global sales in 2008 were $1.0B USD.
Sr. No. / Brand Name / Company
1 / Bandronate Tab & Amp / Roche
2 / Boniva Tab & Amp / GSK
3 / Bandrone Tab / Natco
4 / Bonviva Tab(under license) / Elder
5 / Vebalone / Ranbaxy
Strontium Ranelate
Strontium ranelate, a strontium(II)salt of ranelic acid, is a medication for osteoporosis marketed as Protelos or Protos by Servier. It is unusual in the sense that it both increases deposition of new bone osteoblasts and reduces the resorption of bone by osteoclasts. It is therefore promoted as a "dual action bone agent" (DABA).
Strontium ranelate is registered in more than 70 countries for the treatment of post-menopausalosteoporosis to reduce the risk of vertebral and hip fractures. In the United States, strontium ranelate is not approved by the FDA. In the United Kingdom, the British National Health Service does not use or pay for strontium ranelate as a medicine, because other drugs were determined to be more economical[14].
Two major phase III clinical studies, SOTI (Spinal Osteoporosis Therapeutic Intervention) and TROPOS (Treatment of Peripheral Osteoporosis), were started in 2000 to investigate the efficacy of strontium ranelate in reducing vertebral fractures and peripheral fractures, including hip fractures. In the 3 years results, reported in 2004, strontium ranelate showed significant reduction in vertebral fractures with 41% and hip fractures with 36% compared with patients treated with placebo[14].
The bioavailability of the product is ~25% and its protein binding capacity is found to be 25% for plasma protein and high affinity for bone tissue. As a divalent cation, strontium is not metabolised. Does not inhibit cytochrome P450 enzymes. Half life is 60 hours and excretion is Renal and gastrointestinal. Plasma clearance is about 12ml/min (CV 22%).[16]
Sr. No. / Brand Name / Company
1 / Protelos / Servier
2 / Stronate / Glenmark
3 / Renelate / Shreya Life Sciences
6.3Objectives and Aims of the Study
The study was aimed at achieving the following objectives:

1. To find out the awareness of selected molecules amongst the physicians
2. To find out the acceptance of drugs of the project amongst physicians in treatment practice.
3. To determine the prescription share for each product amongst physicians involved in osteoporosis treatment.
4. To figure out preferred parameters of a drug for treatment of Osteoporosis from physician’s point of view
5. Comparative assessment between two markets in respect to parameters studied.

7. / Material and Methods
7.1 Source of Data
The source of market research will involve:
7.1.1 Primary data: which will be obtained through market research which will be carried out by self-administered questionnaire from randomly selected doctors and chemists
Doctors:
Inclusion criteria: the doctor’s sample will consist of Orthopedics, Endocrinologists, Rheumatologists,Gynecologists and General Practitioners.
Exclusion criteria: the doctors who are specialized in any other discipline other than those
specified above will be excluded from the survey
7.2Method of Collection of Data (Including Sampling Procedure if Any)
Materials and methods:
Sources of data:
a)Primary data:
Through questionnaire method primary data will be obtained from doctors and chemists
b)Secondary source:
The related information will be obtained from:
Text books on disease management
Scientific journals
Pharma biz
Internet
Survey areas:
The survey will be carried out in two cities – Bangalore and Tehran.
Sample size:
The sample size will consist of a total of 200 doctors and 100 chemists.
100 doctors and 50 chemists from Bangalore.
100 doctors and 50 chemists from Tehran.
The doctors’ sample from both the cities will compriseOrthopedics, Endocrinologists, Rheumatologists, Gynecologists and General Practitioners.
7.3Does the study require any investigations or interventions to be conducted on patients or other humans or animals? If so please describe briefly.
Doctors and chemists will be interviewed; hence prior permission of the interviewee will be sought
7.4Has ethical clearance been obtained from your institution in case of 7.3?
Applied for ethical clearance
8. / Bibliography

1. URL: on Nov 6 2009]
2. Randell A, Sambrook PN, Nguyen TV, et al, (1995) Direct clinical welfare costs of osteoporotic fractures in elderly men and women. Osteoporos Int 5:427
3. Lindsay R, Silverman SL, Cooper C, Hanley DA, Barton I, Broy SB,et al. Risk of new vertebral fracture in the year following a fracture. JAMA 2001;285:320-3
4. URL: [Cited on Nov 14 2009]
5. URL: [Cited on Nov 8 2009]
6. URL: on 04 March 2009]
7. Damodaran P, Subramaniam R, Omar SZ, Nadkarni P, Paramsothy M., Singapore Med J. “profile of a menopause clinic in urban population in Malaysia” 2000 Sep; 41(9):431-5
8. URL: on Nov 8 2009]
9. Kotler P. Marketing Management 11th ed 2006. Singapore. Pearson Education Publishers: 129
10. URL:// on Nov 9 2009]
11. Shinkai, I; Ohta, Y “New drugs--reports of new drugs recently approved by the FDA. Alendronate”. Bioorganic & medicinal chemistry. Jan 19964 (1): 3–4.
12. URL:

=mimssearch&searchstring=strontium+ranelate&CTRY=IN[Cited on Nov 8 2009]

1. URL: on Nov 8 2009]
2. Technology appraisal: Osteoporosis - primary prevention, National Institute for Health and Clinical Excellence. Retrieved on 2007-10-27
3. Meunier PJ, Roux C, Seeman E, Ortolani S, Badurski JE, Spector TD, Cannata J, Balogh A, Lemmel EM, Pors-Nielsen S, Rizzoli R, Genant HK, Reginster JY "The effects of strontium ranelate on the risk of vertebral fracture in women with postmenopausal osteoporosis". New England Journal of Medicine - 2004.350 (Jan 29): 459–468. doi:10.1056/NEJMoa022436. PMID14749454
4. URL: on Nov 8 2009]
5. URL: on Nov 10 2009]

9. / Signature of Candidate: / SAEED AKBARIAN
10. / Remarks of the Guide / Recommended for Approval
11. / Name and Designation of:
11.1 Institutional Guide
` / Dr. V. KUSUM DEVI
Professor & Head
Dept. of Pharmaceutical Marketing and Management
Al-Ameen college of Pharmacy
Signature
11.2 Institutional Co. Guide / Dr. Roopa S. Pai
Professor
Dept. of Pharmaceutics
Al-Ameen College of Pharmacy
Signature
11.3 Head of the Dept / Dr. V. KUSUM DEVI
Professor & Head
Dept. of Pharmaceutical Marketing and Management
Al-Ameen college of Pharmacy
Signature
12. / Principal
12.1. Remarks of the Principal
Signature / Forwarded for the University
Prof. B. G. SHIVANANDA
Principal
Al-Ameen College of Pharmacy
Hosur Road, Bangalore-560 027

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