Case 2: A 12-year-old African-American girl had a long history of severe, persistent asthma beginning at 14 months. She was hospitalized numerous times, and had required intubation and mechanical ventilation three times for acute severe asthma exacerbations. Long-term prednisone was required since the age of 8 years (Table 1). On hospital admission, medications included 10 mg of prednisone administered on alternate days, high-dose inhaled glucocorticoids, and theophylline. Her evaluation is summarized in Table 2.

Serial spirometry revealed diurnal variation in FEV₁ values ranging from 75 to 103% of predicted (Fig 1, center, B). A prednisone burst resulted in a significant reduction in diurnal variability. Bronchoscopy with endobronchial biopsy was performed after 2 weeks of daily prednisone. Airway anatomy was normal while the airway mucosa was markedly inflamed and friable. The BALF cell differential was abnormal, with a substantially increased percentage of neutrophils (22%; normal, 1.5 to 2.1%) and lymphocytes (28%; normal, 8.9 to 10.1%) with an accompanying reduction in the percentage of macrophages (50%; normal, 87 to 89%); no eosinophils were present. Biopsy showed a partially denuded epithelium, squamous metaplasia, goblet-cell hyperplasia, markedly thickened subbasement membrane, and a significant quantity of elastin fibrils immediately below the basement membrane (Fig 3, Table 3).

Medical ethicists examine aggressive marketing tactics’ influence on medical practice and outline strategies to protect patients

Drugs that pharmaceutical companies market most aggressively to physicians and patients tend to offer less benefit and more harm to most patients – a phenomenon described as the “inverse benefit law” in a paper from the University of Texas Medical Branch at Galveston.

Published online Thursday, Jan. 13 in the American Journal of Public Health, the article explores recent withdrawals of blockbuster drugs due to safety concerns and finds a clear pattern of physician-focused marketing tactics that ultimately exposed patients to a worsening benefit-to-harm ratio. Potential patient safety and public health implications include unnecessary exposure to adverse side effects, high medical costs and competition for scarce resources.

“This is not a random occurrence, but rather a repeating, planned scenario in which drugs, discovered with good science for a specific set of patients, are marketed to a larger population as necessary, beneficial and safer than other alternatives,” said co-author Dr. Howard Brody, a professor and director of the Institute for the Medical Humanities at UTMB Health. “Marketers are just doing their jobs. However, the reality is that for most new drugs, safety and efficacy are scientifically proven for only a small subset of patients. It’s time for physicians to take a stand and not prescribe them so readily.”

Macrolides Mixed With BP Drugs Can Lead to Hypotension

Simultaneous use of calcium-channel blockers and some macrolide antibiotics may result in hypotension, which may require hospital admission, according to a study published online Jan. 17 in CMAJ, the journal of the Canadian Medical Association.

MONDAY, Jan. 17 (HealthDay News) — Simultaneous use of calcium-channel blockers and some macrolide antibiotics may result in hypotension, which may require hospital admission, according to a study published online Jan. 17 in CMAJ, the journal of the Canadian Medical Association.

Alissa J. Wright, M.D., from the University of Toronto, and colleagues conducted a population-based study involving patients aged 66 and older who were prescribed a calcium-channel blocker between 1994 and 2009. The investigators identified which of the patients had been hospitalized for low blood pressure and whether they had been prescribed a macrolide antibiotic shortly before their admission.

The investigators identified 7,100 patients who were hospitalized with hypotension during treatment with a channel-blocker, of whom 176 had been prescribed a macrolide antibiotic. Erythromycin and clarithromycin were associated with hypotension (odds ratios, 5.8 and 3.7, respectively). Azithromycin was not associated with an increased risk of hypotension.

“Clinicians should be aware of the potential interaction between these drugs. When a macrolide is required, preferential use of azithromycin should be considered in patients already receiving a calcium-channel blocker,” the authors write.

Two of the study authors disclosed financial ties with pharmaceutical companies.

A proposal by the U.S. Pharmacopeial Convention aims for greater flexibility in the preparation of radiopharmaceuticals for use in positron emission tomography. The USP has proposed quality assurance revisions to the general chapter for production and compounding.

The revision covers PET drugs for human administration, and among its goals is easing production requirements for drugs used in research. It complies with state-regulated pharmacy compounding practices and other regulatory requirements. And it mirrors the FDA’s final PET GMP rule and guidance.

USP notes that PET drugs have come a long way since the original monograph was written in 1989. Drivers for the revision include the greater number of PET drugs, higher production levels, shorter synthesis and QC times and more complex synthesis processes.

According to USP, the revision will ensure that drug identity, strength, quality and purity are uncompromised.

Growth of Generics Industry Remains Upbeat in Canada

As per our latest research report “Generic Drug Market in Canada”, the Canadian generics industry is anticipated to show healthy growth rates in coming years and is projected to witness a CAGR growth of around 14% during 2009-2013. Future of the industry remains promising owing to higher margins and lower competition in Canada compared to other big markets. We have found that the growth in the generics industry will be mainly driven by ageing population, patent expiry of several blockbuster drugs, and the government support in the form of cost containment. Besides, high participation in industry activities by the market players, higher margins to pharmacists, and effective developmental efforts
Our research indicates that presently the share of generic drugs in Canada is about one-fourth of the overall pharmaceutical market. Besides, many foreign firms are looking forward to invest in the Canadian generics industry. Some key therapy areas such as, chronic disease, hypertension, and diabetes represent big opportunity for generic drug manufacturers in Canada. We have also evaluated various factors that will propel the growth of generics market in Canada during the forecast period (2011-2013).

The report “Generic Drug Market in Canada” is a complete source of knowledge and analysis regarding the Canadian generic drugs sector with complete emphasis on data reliability and authentication. The report has covered every important aspect of the generic drug market and elaborated significant proportion of the current market trends along with their future outcome. Sections like, ‘generics market performance’ and ‘regulatory environment’ provides an in-depth market analysis and key activities by the government respectively. These sections measure industry in terms of key statistics and current regulatory mechanisms that have a major impact on current revenue patterns and future growth.

The report is an outcome of an in-depth research and prudent analysis of the Canadian generic sector with effective presentation and forecasting in key areas. The forecasting in report relies on suitable methods and techniques that further enhance reliability in future projection. Moreover, the major activities and description of market players have been elucidated in the report.

TORONTO — A complaint about perceived drug industry involvement in a pain management course for medical students has prompted the University of Toronto to revamp its curriculum.

An informal inquiry into the complaint about potential conflict of interest, lodged earlier this year by an unidentified student and two doctors in the faculty of medicine, has set out clear guidelines about how the course should be taught, by whom and with what sources of funding.

The complaint centred around students being provided a book on managing chronic pain that was funded and copyrighted by the maker of the prescription pain killer OxyContin. The book had been brought in by a non-faculty lecturer with financial ties to the drug company.

In a report obtained by The Canadian Press, inquiry head Lorraine Ferris says “time is of the essence” in revising the interfaculty pain curriculum, a 20-hour course jointly taught to medical, dental, pharmacy and nursing students.

Ferris, associate vice-provost in the department of Health Sciences Policy and Strategy, said by email that she found no evidence of wrongdoing or actual conflict of interest. “However, I was troubled by the perception of conflict of interest and therefore my recommendations … addressed this issue.”

She said planning for the revised curriculum needs to begin quickly, in time for delivery of the next course this spring.

“To revise the interfaculty pain curriculum, the sessions on pharmacotherapy of pain must include delivery of balanced information by experts in several fields, including pharmacology and opioid addiction,” she writes in her report.

“As part of their discussions, faculty will need to address important, topical and often sensitive issues regarding opioids, including, for example, opioid addiction, improper opioid prescribing, at-risk communities, illicit sales and drug diversion, ‘double-doctoring’ and recreational sharing and use of opioids.”

Dr. Rick Glazier, whose 18-year-old son died last year of an accidental overdose of the highly addictive OxyContin, and Dr. Philip Berger are both physicians at St. Michael’s Hospital, one of the University of Toronto’s teaching hospitals. The two doctors asked for an inquiry into the pain course after being approached by the medical student.

Berger said he is pleased with Ferris’s report, which “has met our concerns head-on.”

“She’s raised very serious issues of conflict of interest and made what I think is an absolutely correct statement that not only the academic community but the public more generally would find making a copyrighted and owned drug-company textbook available to students objectionable, regardless of how its assessed quality is,” he said.

“To me, and I think quite correctly, she’s called for a higher standard in a public policy area of a very high profile and of interest to both government and the public. I think it’s fair to say that the implementation of Prof. Ferris’s recommendations will make the public safer and likely will save lives.”

In often bluntly worded statements, Ferris recommends that curriculum development and accountability for the course be transferred from the Centre for the Study of Pain to the Centre for Interprofessional Education and that only University of Toronto faculty members teach the course.

Dr. David Mock, dean of dentistry at Canada’s largest university, said the four faculties involved in the centre are in the process of implementing the recommendations.

“I think this is a good thing,” said Mock. “I’m not looking at this as a hand-slap for the centre. I think what we’ve done is move it into the more modern governance system that we are developing at the university.

“The course will still be run by the people who know the most about the topic and that’s the people from the Centre for the Study of Pain. The course hasn’t been taken away from them.”

Ferris’s report also said the curriculum should not be “directly funded (in whole or in part) by industry donors who have, or may have, or be perceived to have financial interests in the assessment or management of pain.”

From 2002 to 2006, the pain course was funded by donations, included $117,000 in unrestricted educational grants from four drug companies — Merck-Frosst, Purdue Pharma, Pharmacia Canada and Pfizer — although they had no input into course content. Since 2007, the program has been funded solely from faculty budgets.

Mock said Purdue’s copyrighted book on pain management had been brought in by Dr. Roman Jovey, an unpaid guest lecturer and co-author of the book who left copies “for anyone to take.” Jovey, medical director for a chain of clinics called the Centres for Pain Management, is a member of Purdue’s speakers’ bureau, paid by the company to conduct workshops and lectures.

“It wasn’t distributed by the program,” Mock said of the book. “But we stopped that because, again, there’s reality and there’s appearances and it appeared as if we were pushing the books, so to speak. So we stopped doing that, we stopped before the inquiry.

Jovey confirmed he had left copies of the 371-page book, entitled “Managing Pain: The Canadian Health Care Professionals Reference,” for students.

“It was a gift from Purdue. I’m not at all embarrassed or ashamed. I think it’s a darn good book.

“If we all want to be politically correct and have the appearance of being politically correct, then I guess I get it, that nothing that has any kind of pharma logo or name or ownership should be given out to medical students,” he said Wednesday.

“But the losers are the medical students because I think it’s a high-quality book, it’s very readable and they’re deprived of it this year because of this controversy. And I guess they will be in the future.”

Jovey, director of the addiction and concurrent disorders centre at Credit Valley Hospital in Mississauga, Ont., said he stands behind the material in the book and “would debate anybody about that.”

However, Dr. Irfan Dhalla said he has concerns about the content of the book, which a medical student taking the course brought to his attention.

“There are definitely things that are not consistent with the evidence,” said Dhalla, a staff physician at St. Michael’s Hospital and a lecturer at the university. “For example, oxycodone … is listed as a moderate-potency opioid, when I think everybody agrees it’s a very strong opioid, up to twice as strong as morphine.”

While it’s appropriate to prescribe oxycodone for severe acute pain or cancer pain, Dhalla said the book suggests that physicians can prescribe the drug for chronic non-cancer pain with relative safety for the patient.

“And I think people with experience know that that is just not the case. When you prescribe to people with chronic non-cancer pain, it’s very difficult to do that safely,” he said, noting that the book pays little attention to issues of addiction and deaths from overdose.

“The book in several places makes reference to a claim that the rates of addiction if opioids are used for chronic non-cancer pain are very low. And they’re not nearly as low as is claimed in the book.”

In fact, a study by Dhalla and colleagues published last year showed prescription rates for opioids — including OxyContin, a long-acting form of oxycodone — soared in Ontario over the last two decades, as did the number of deaths linked to the narcotic.

What’s of greatest concern, of course, is how such information imparted to medical students as part of their curriculum will affect prescribing practices once they become doctors.

“Does it influence medical students? Absolutely. There’s no doubt that it does,” said Dhalla. “I think there’s definitely been a shift over the last 10 or 15 years in the way medical students have been taught about pain and opioids, and often you will find on the wards that the medical students and residents are much more liberal with opioids than the older physicians.”

The issue of the pharmaceutical industry possibly influencing medical school curriculum isn’t restricted to the University of Toronto, but has been an issue for universities across North America. An investigation published this week by ProPublica, an independent non-profit news organization, found faculty members from at least half a dozen U.S. medical schools — including Stanford — were paid speakers for drug companies, despite conflict of interest guidelines.

Leaving aside the U of T’s pain curriculum, Berger said the report raises the issue of the pharmaceutical industry potentially affecting undergraduate medical education in general.

“The danger is an obvious one. It is in the interests of the drug company to have physicians prescribing as many opioid medications to as many patients as possible. It’s the only way it makes its money.”

“So it raises a very serious question about whether industry-sponsored speakers or materials should ever be used in undergraduate medical education because the primary interest of the pharmaceutical industry who makes these drugs is to have people on the drugs — not to educate students properly.

“This would apply to any disease that requires medications.”

Deregulation for consumers

A man who suffered indigestion in the wee hours of the morning visited several drugstores, though most were closed, to buy medicine. He recalled memories of conveniently purchasing over-the-counter drugs that do not require prescription in his trips to the U.S. or Europe. He grew angry over the trouble in searching for a drugstore that was open. If the government wants to ease such inconvenience, it needs to allow the retail sale of over-the-counter drugs. Such drugs are displayed at the sales counter of a pharmacy, which give consumers easier access to medicine. In Korea, some have demanded since 1993 the legal sale of over-the-counter drugs at retail stores. The Health and Welfare Ministry also repeatedly promised to seek implementation of the system but nothing has changed.

Pharmacists’ groups, which oppose the sale of over-the-counter drugs at retail outlets, give the excuse of the possible overuse and misuse of drugs. Former Health and Welfare Minister Jeon Jae-hee took the pharmacists’ side, saying, “The public encounters little inconvenience because there are more drugstores than supermarkets in Korea.” According to a survey conducted in March by the Korea Chamber of Commerce and Industry, 70 percent of respondents said they “experienced inconvenience because of trouble finding a pharmacy open at night or on holidays.” Singled out were digestives, painkillers, cold medicine, disinfectant, tonic beverages and vitamin as items they wanted retail stores to sell. The ministry, which is supposedly in charge of public health and well-being, is effectively guarding the interest of the pharmacists’ community while disregarding public inconvenience and need. Seoul National University professor Kwon Yong-jin said, “This situation has been caused by the ministry being cajoled by the pharmacists’ community over the past 10 years since the separation of diagnosis and prescription of medicine.”

In a briefing on next year`s business plan by the ministry Wednesday, President Lee Myung-bak asked, “In countries like the U.S., people can buy drugs at supermarkets. What is the situation in Korea?” Health Minister Jin Soo-hee failed to give proper examples of foreign countries. The reality is that the U.S., Europe and Japan allow the sale of over-the-counter drugs at retail stores. The U.S. specifically defines the type and scope of medicine that consumers can purchase at retail stores, including supermarkets, convenience stores and gas stations. Japan approved the retail sale of certain drugs in 1998, and allowed the sale of about 95 percent of over-the-counter medicine at retail stores from June last year.

Public benefits oftentimes suffer a setback due to regulations that protect the interests of an industry. Measures designed to allow capital investment in and expand the scale of a sector requiring professional licensing, including optician’s stores, have hit a snag as well. The cap on daycare center fees, which was set to enable everyone to use daycare facilities, brings down the quality of such facilities and disrupts the diversification of daycare services. The government needs to drastically remedy regulations on the service industry to raise consumer convenience and benefits.

The pharmaceutical industry’s effort to find new ways of discovering and developing drugs has been underway for most of this decade, but it remains a struggle.

The latest sign is the replacement of Marc Cluzel as Sanofi-Aventis’s head of research by Eliaz Zerhouni, an adviser to the company’s chief executive, Chris Viehbacher.

The FT reports:

Since his appointment as scientific adviser to Mr Viehbacher in February 2009, the company said Mr Zerhouni had been “instrumental in redesigning the R&D model to foster increased innovation … [to] provide innovative solutions in response to specific, unmet needs of patients.”

It stressed the development – in line with similar measures taken by its peers in recent years – of scientific networks and openness to the external scientific world.

For as long as I have taken an interest in the industry – about eight years – it has been dominated by the same story – the crisis of patent expiry on the blockbuster drugs of the 1990s, and the need to somehow replenish the pipeline.

The change at the top of Sanofi-Aventis follows the resignation of Jeff Kindler as chairman and chief executive of Pfizer, on the grounds that he was exhausted by the job.

Some day, things will improve for big pharma but that day still looks a long way off.

‘West Bengal pharma sector has tremendous scope for growth and development in the coming years’

With decades of experience under his belt, Subharthee Dey needs no introduction. Former Vice-President, Indian Drug Manufacturers’ Association (IDMA) and Whole Time Director, Dey’s Medical Stores (Mfg) Ltd ( Dey’s Medical Stores) shared with Express Pharma the challenges and possibilities of the pharma industry in West Bengal and how he was instrumental in the five-decades old Dey’s Medical into a professionally run company.

Please share your views on West Bengal pharmaceutical industry, how optimistic are you about its future?

It is a well fact that Bengal’s tryst with the pharma industry could be traced back to the early 20th century when Acharya PC Roy, the visionary set up Bengal Chemicals and Pharmaceutical Works Ltd. Till the later part of the last century, Bengal held on to its leadership position but due to factors beyond control, it lost its place in the national perspective and our western counterparts seized the opportunity. So, inspite of being a sizable market for pharmal products, West Bengal’s contribution in terms of production slipped to an abysmal low.

But things have started changing in the recent past, efforts are on to revive the pharma sector in the state. Today, there has been a positive change in the attitude and mindset of the industry and the local pharma manufacturers are making all out efforts to make their presence felt in the national pharma arena. New entrepreneurs too have started entering the fray. I feel that the West Bengal pharma sector has tremendous scope for growth and development in the coming years.

What are the factors ailing the pharma industry in the state?

We were perhaps a little pre-occupied in preserving what little we have done and basking in the glory of our founding fathers rather than reworking our strategies to fight the onslaught posed by the new patent regime or by the MNCs. But better sense prevailed and they have taken lessons from their mistakes. They have realised the potential of the sector and re-oriented their strategies accordingly. Since then the scenario has changed rapidly in the last one decade and has become much more competitive than what it was in the early 70s.

Do you think it can emerge as a pharma hub in the region?

Why not. As you aware that human resource plays a very crucial role in knowledge-based industries like pharma and biotechnology, West Bengal biggest’s strength is its huge pool of educated human resource. The State houses some of the leading research institutes and Universities in the country. A favourable industrial climate, uninterrupted power supply, a stable and conducive socio-political environment, improved infrastructure facility and with a pro-active administration the state can become an ideal investment destination.

Tell us about Dey’s Medical Group, one of the leading and earliest entrants in this sector, which is operating from the state for more than 50 years now and how it

The 52-year old Dey’s Medical, which commenced commercial production of pharma formulations in January 1958, has been pursuing its goal to become a company with a high growth in its present segments of business.

Over the last few years, we completed the modernisation and refurbishment exercise of our existing pharma manufacturing facility in Kolkata. The facility manufacturing different dosage forms of drugs like capsules, tablets, oral liquid, drops, etc has been completely mechanised. Today, our manufacturing facilities conform to all the latest quality norms.

During the process of revamping it was felt that our manufacturing facility was over-staffed, so we effectively re-deployed and brought down our total workforce through a process of dialogue.

We replicated the same model in revamping our sales and marketing team. It was felt that our marketing team was falling behind our competitors due to the age-factor, so we reorganised the set up. Now we have brought down the average age to 35 years, which was above 50 years. The company also hired trained and skilled manpower to strengthen its sales and marketing team.

Young talents from technical institutes and colleges of the city are also undergoing intern programs at our facilities.

Another major development has been the deployment of technology in all spheres of our operations be it manufacturing, quality control, testing, administration etc. We have invested heavily on setting up technology backbone.

These initiatives have started showing results. We believe that we will be able to carry forward our growth momentum in the coming years.

On the product development front, we have introduced new molecules, ayurvedic and OTC products, which have been widely accepted by the consumers and the medical fraternity.

How you have strengthened your R&D efforts?

In the last few years, we have strengthened our in-house R&D activities. The fully equipped R&D Department is engaged in continuous development work on new formulation developments and improving process technology.

The company has also tied up with Indian Institute of Chemical Biology (IICB), a CSIR unit for development and standardisation of Ayurvedic formulations.

What pill do you like to prescribe for the growth of the regional players?

In West Bengal majority of the pharma companies are dependent on the government institutional business. It should not be the case. The pitfalls of the governmental business thwart the development and growth of the unit.

I believe that inspite of all the challenges and limitations, the Indian pharma industry looks very positive and holds opportunities for the local players. In order to seize the opportunities, they need to re-orient their strategies. The regional players need to strengthen their marketing initiatives, increase their product basket and concentrate on creating newer brands. They can explore possibilities like co-marketing, co-branding, EMR exercises to increase their bottomlines. Then only they can survive and grow in this competitive era.

Another area which is ignored by most of the pharma entrepreneurs is the speciality drugs sector which has a vast scope for growth.

The State Government too has a very important role to play in this direction. The industry not only needs direction but also guidance and support from the state government.