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There appears to be a conflict of interest if pharmaceutical companies promote life-long drug treatment for obese children. Would the conflict of interest be mitigated if the promotion was supported by the American Academy of Pediatrics?
I am sure that there is nothing financially sweeter to a pharmaceutical company than to promote a life-long drug treatment for children especially when supported by the American Academy of Pediatrics (AAP). This issue is not something that I made up for discussion but it appears to be real and when first set as Policy in 2008 had set off a controversy. I can't find that the policy of the AAP has been subsequently revised.
The medical significance of obesity in children is found in the extract below from the Perspective section of the September 25, 2008 issue of the New England Journal of Medicine and available as a free full article http://www.nejm.org/doi/full/10.1056/NEJMp0805953 titled
“Storm over Statins — The Controversy Surrounding Pharmacologic Treatment of Children” by Sarah de Ferranti, M.D., M.P.H., and David S. Ludwig, M.D., Ph.D.
"During the past 25 years, the prevalence of pediatric obesity has tripled; in some minority-group populations, the majority of adolescents are overweight or obese. Recent research suggests that increasing body weight in childhood, even within the range considered normal, is strongly associated with the risk of cardiovascular disease in adulthood. Case reports have identified renal failure requiring dialysis, limb amputation, and death before 30 years of age among persons who developed type 2 diabetes during adolescence. Because of such effects, some experts have predicted that life expectancy will decrease in the United States for the first time in more than a century unless something is done about childhood obesity."
As you will read in the article, in 2008 the American Academy of Pediatrics released a revised recommendation for the management of elevated cholesterol in children based on evidence that hardening of the arteries begins in childhood and the treatment with statin drugs which lower the cholesterol in adults may reduce the chances that the child will later develop coronary artery disease or other diseases of the arteries. It is suggested by the recommendations that screening for fats in the blood begin at age 2 and drug therapy for elevated LDL (“bad cholesterol”) may begin in 8 year old children. This would be in addition to attempt to prevent or reduce childhood obesity through control of diet and exercise. The “storm” and the ethics regarding the recommendation is related first to the unknown harm on normal physiologic development in children when cholesterol levels are reduced. Is starting a medication in a child with its physiologic consequences unknown ethical? Also a "slippery slope" may begin so that other cardiovascular and metabolic medications given to adults will be started in children as preventatives for heart disease, hypertension and diabetes. Slippery slopes raise ethical concerns about laxity regarding further unknown harms with these medications. Remember, controlled research studies are far less common in children than in adults. As I have written as the title of this Medpedia Question, an ethical concern relates to whether pharmaceutical companies can rid themselves of their conflict of interest when they are evaluating the role of these drugs for use in prevention of the adult disease. After all, starting a life-long medication in childhood has a better financial outcome for the company than starting the drugs only when the child becomes an adult.
In addition, open to discussion is who is responsible for obesity in children? Simply genetics, the parents, the schools, society in general? Should the professional guidelines for treatment of obese children with drugs trump the need for the parents and others to attend to the proper nutritional and activity factors to prevent childhood obesity and its consequences? ..Maurice.
The medical significance of obesity in children is found in the extract below from the Perspective section of the September 25, 2008 issue of the New England Journal of Medicine and available as a free full article http://www.nejm.org/doi/full/10.1056/NEJMp0805953 titled
“Storm over Statins — The Controversy Surrounding Pharmacologic Treatment of Children” by Sarah de Ferranti, M.D., M.P.H., and David S. Ludwig, M.D., Ph.D.
"During the past 25 years, the prevalence of pediatric obesity has tripled; in some minority-group populations, the majority of adolescents are overweight or obese. Recent research suggests that increasing body weight in childhood, even within the range considered normal, is strongly associated with the risk of cardiovascular disease in adulthood. Case reports have identified renal failure requiring dialysis, limb amputation, and death before 30 years of age among persons who developed type 2 diabetes during adolescence. Because of such effects, some experts have predicted that life expectancy will decrease in the United States for the first time in more than a century unless something is done about childhood obesity."
As you will read in the article, in 2008 the American Academy of Pediatrics released a revised recommendation for the management of elevated cholesterol in children based on evidence that hardening of the arteries begins in childhood and the treatment with statin drugs which lower the cholesterol in adults may reduce the chances that the child will later develop coronary artery disease or other diseases of the arteries. It is suggested by the recommendations that screening for fats in the blood begin at age 2 and drug therapy for elevated LDL (“bad cholesterol”) may begin in 8 year old children. This would be in addition to attempt to prevent or reduce childhood obesity through control of diet and exercise. The “storm” and the ethics regarding the recommendation is related first to the unknown harm on normal physiologic development in children when cholesterol levels are reduced. Is starting a medication in a child with its physiologic consequences unknown ethical? Also a "slippery slope" may begin so that other cardiovascular and metabolic medications given to adults will be started in children as preventatives for heart disease, hypertension and diabetes. Slippery slopes raise ethical concerns about laxity regarding further unknown harms with these medications. Remember, controlled research studies are far less common in children than in adults. As I have written as the title of this Medpedia Question, an ethical concern relates to whether pharmaceutical companies can rid themselves of their conflict of interest when they are evaluating the role of these drugs for use in prevention of the adult disease. After all, starting a life-long medication in childhood has a better financial outcome for the company than starting the drugs only when the child becomes an adult.
In addition, open to discussion is who is responsible for obesity in children? Simply genetics, the parents, the schools, society in general? Should the professional guidelines for treatment of obese children with drugs trump the need for the parents and others to attend to the proper nutritional and activity factors to prevent childhood obesity and its consequences? ..Maurice.
asked Apr 10, 2011 at 09:52PM in Other
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1Votes
answered Apr 11, 2011 at 10:53PMRegarding conflict of interest: it would depend on the relationships between the American Academy of Pediatrics and the pharmaceutical industry in part. A real effort would be required to demonstration separation. But it would be a step in the right direction.
That said, I am very unenthusiastic about lifelong pharmacotherapy for weight control. It is certainly unlikely to be as safe, or as effective, as doing what it takes to help kids make better use of their feet and their forks.
Regarding responsibility, it's an issue I've wrestled with quite recently; please see: http://www.liebertonline.com/doi/abs/10.1089/chi.2011.0101 -
1Votes
answered Apr 12, 2011 at 05:33AMA life-long drug therapy for children is a dream-come-true for any drug manufacturer, but is it yet another example of what's been called "marketing-based medicine"?
Most research in support of statins is funded by those who sell statins, including the JUPITER trials published in 2008. JUPITER was funded by AstraZeneca, the very drug company that makes Crestor (the darling of the statin world, linked in the JUPITER trials with reducing CRP inflammation markers). In fact, nine of the 14 authors of the JUPITER study have financial ties to AstraZeneca. The lead author Dr. Paul Ridker also holds the legal patent on CRP blood-testing technology that stands to explode in sales if his JUPITER study’s recommendations are accepted by cardiologists worldwide. The inherent conflict of interest is clear and disturbing.
Industry influence is not limited to statin marketing. Consider the work of Dr. Mohammed Hassan Murad of Mayo Clinic, who reviewed 202 published medical journal articles that addressed the now-recognized association between heart attack risk and the GlaxoSmithKline diabetes drug, Avandia. 86% of study authors who wrote positive reviews had financial relationships with GSK. Among authors of articles offering unfavorable reviews, only 18% had relationships with GSK.
As Dr. Katz wisely says, it's the kids' feet and their forks that need the endorsement of the AAP, not the marketing interests of Big Pharma. See also: "How Big Pharma Spends $20 Billion A Year On Marketing Their Drugs To You" at: http://ethicalnag.org/2010/02/10/20-billion-marketing/ -
2Votes
answered Apr 12, 2011 at 09:54AMConflict of interest is one of the most interesting ethical issues. You might start by asking "What are the obligations of a professional association to its stakeholders?"
If the AAP's stakeholders include kids, and if the standard of care for pediatric obesity was life-long drug treatment, then there would be little or no conflict.
However, those "ifs" are not the case.
A common way to mitigate conflict of interest is to disclose it. Our studies on physician financial ties to pharma in postmarketing research: http://www.ncbi.nlm.nih.gov/pubmed/7795459 and physician disclosure http://www.ncbi.nlm.nih.gov/pubmed/10134417 in research suggest that disclosure is sometimes not enough. Since that BMJ publication, there has been more disclosure, but I don't know if there has been more resolution.
Obesity is the most important public health issue in developed countries and arguably in many "emerging markets", including China and India. It's also a very recent phenomenon.
We need to be much more creative in our response to it than endorsing life-long pharmacotherapy, especially when it has been unsuccessful and so problematic in adults. -
1Votes
answered Apr 12, 2011 at 10:39AMIt is a fact that the pharmaceutical and biotechnology industry is a major sponsor of research at top universities, medical schools, leading hospitals, medical congress, educational courses, clinical trials, professional associations, patient advocacy group and top medical journals. In the time of budget crisis, funds from industry are welcomed by a majority of institutions and organizations. Existing disclosure rules are sufficient for transparency.
The American Academy of Pediatrics must have received educational grants or its panel of experts have financial ties with industry. There is a push from many quarters to push industry to develop new drugs to treat childhood obesity. The FDA grants additional 6 months of patent protection for use in pediatric patients. If a new safe and effective weight loss drug was available and approved by the FDA for adults. can it be used off label in adolescent children? -
1Votesanswered Apr 12, 2011 at 11:37AMTo be clear about which COI I was thinking about as I wrote the Question, I have always assumed, most likely naively, that pharmaceutical companies have one stakeholder which should trump all others: the public and in the example discussed.. all the children. Now, if the pharmaceutical company is primarily looking toward a life-long therapy schedule of their drug as a benefit to their business stakeholders, that, to me, would represent a malignant conflict of interest. So I thought, well..if the AAP concurs that this should, hopefully based on research, be a standard of pediatric practice then maybe I shouldn't be so harsh in my opinion of the pharmaceutical company's conflict. But now if the AAP policy is not based strictly on research conclusions but also on some financial benefit from the pharmaceutical company.. well...that wouldn't be so ethical. Can anyone find in the literature since 2008 what was the outcome of the "controversy" in terms of current practice advice? ..Maurice.
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0Votesanswered Apr 12, 2011 at 11:27PMMaurice,
Are you advocating an outright ban on all pharmacologic treatment for obese children even when other options like counseling, education, increased physical activity, regular sport activity, dietary and lifestyle changes have failed?
I think that use of generic statins and weight loss drugs as adjunct or add on therapy option should remain along with surgery for obese children. Millions of patients worldwide have used statins to lower cholesterol and CV risks. Can parents or healthcare providers be sued by children for denial of an effective pharmacologic treatment? So it is not a simple COI related to pharmaceutical
Carolyn
There are many incentives from government, regulators, funding agencies and venture capital to fund industry to develop treatments for children’s disease. I do not have specific as I have not followed R&D in this indication. There are over 60 new drugs in clinical trials for obesity and metabolic syndrome. -
0Votesanswered Apr 13, 2011 at 07:21AMDr. Maggon - Readers here should be made aware of your own pharmaceutical company conflicts of interest as noted in your bio, which boasts of, among other accomplishments, helping your drug clients to achieve "..peak sales of some of the drugs worked on was >6.5 billion dollars..." Congratulations to you and your Big Pharma employers.
For example, you describe obese children for whom "other options like counseling, education, increased physical activity, regular sport activity, dietary and lifestyle changes have failed?" Really? How many children are we talking about here? Please share your sources for these chldren for whom lifelong obesity drugs are the only option.
Let's take a small step backwards and think about what is actually being said here. Can you seriously be endorsing lifelong drug therapy for obesity starting in childhood? If so, you are clearly Big Pharma's best friend.
Consider instead the Center for Science in the Public Interest and their "Integrity In Science" conflict-of-interest project, that shows strong evidence that researchers’ financial ties to chemical, pharmaceutical, or tobacco manufacturers directly influence their published positions in supporting the benefit or downplaying the harm of the manufacturers’ product. More on this at: "Integrity in Science: Who's Paying The Piper?" http://ethicalnag.org/2011/01/27/integrity-in-science-report/
Dr. Bernstein, you might be especially interested in learning more about this project if you are still naively trusting that Big Pharma's only stakeholder is the poor patient.
As disturbing as this CSPI database may be to health care consumers, merely disclosing all your financial conflicts of interest is not enough. Disclosure (usually mandated, rarely voluntary) merely reveals who is on the take from those most invested in marketing-based medicine, and somehow purports to absolve those with financial ties influenced by industry. Many doctors dutifully disclose long lists of their industry partners without batting an eyelash over the inherent inappropriateness of such financial relationships. Dr. La Puma points out that it's questionable to assume that disclosure = mitigation.
And as Dr. Marcia Angell of Harvard Medical School (and former editor of The New England Journal of Medicine for two decades) told The New York Times:
“Pervasive conflicts of interest corrupt the medical profession - not in a criminal sense, but in the sense of undermining the impartiality that is essential both to medical research and clinical practice.” -
1Votesanswered Apr 13, 2011 at 09:34AMKrishan, you wrote "Millions of patients worldwide have used statins to lower cholesterol and CV risks." but have sufficient children been followed for the many years necessary to determine the safety and efficacy of the statins? Drugs acceptable as therapy in adults for limited times such as 20 years may behave differently when started in an 8 year old child. I don't think that efficacy and safety can be so readily established for a child. ..Maurice.
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0Votesanswered Apr 13, 2011 at 10:33AMMaurice,
I do not know the exact figures but believe there is sufficient data about the use of Lipitor® (atorvastain, Pfizer) and other statin in children. This is because all the statins like Zocor, and Lescol/Pravachol had 6 months patent extension for pediatric use before going generic. Similarly Lipitor has received 6 months extension for pediatric use and its patent expires on 30 November, 2011.
The first clinical trials of atorvastatin were done last decade in children with a rare genetic defect which impaired ability to clear cholesterol. With children inheriting 2 copies of the defective gene (1 from each parent), cholesterol levels are >600 mg/dL compared to normal levels of < 200 mg/dL. Such children suffer heart attacks or undergo bypass surgery by their teens. The average life span is 14 years! Zocor® (simvastatin, Merck) was tried in this group of children and failed to lower cholesterol.
Among 10 such children in the clinic in South Africa was a youngster named Andre who had a cholesterol level of 1,100 mg/dL. He had tell-tale signs of the condition: tiny lumps of cholesterol deposits just under the skin between his fingers and around his knuckles.Within a month of starting on Lipitor, the children's cholesterol started coming down. Andre's dropped to about 700 mg/dL; that of others, who didn't start so high, fell much lower. Atorvastatin was the first effective statin to work in this group. Andre died late 1999 of a heart attack at age 10, four years after he began taking the drug. His cholesterol never came down to near normal, but several other young patients continue to do well.
The South Africa results were enough for the FDA to put Lipitor on priority review. The company enrolled the last patient in its major trial in October 1995 and filed for approval in June 1996. Six month later, Lipitor was cleared to begin sales.
http://www.oralchelation.net/data/Cholesterol/data11d.htm -
1Votes
answered Apr 14, 2011 at 12:42AMGood day,
Presuming that a child is otherwise healthy except for overweight/obesity, I find no reason to prescribe drugs (preventative, life long, or otherwise) what they need is to "get the lead out" (my dad's favorite saying) and move around. If there is a medical condition present that is another story and it would be up to the parents and doctors to plan the best course of treatment.
If this were the only solution humankind could device to combat childhood obesity, I would suggest we are not dealing with the real issues faced by minority members in our society, nor are we helping the situation by presenting drug as a solution. Historically, prescription take a lot of money to create and are very expensive. The generic Statin may be affordable now, but the pharmaceuticals company will (WILL) change a molecule or two and the price for the new drug will become unmanageable for the family or for the health care system.
We cannot deny we live in a capitalistic society, so yes, every company is going to try and find a solution (in their respective ways) to the problems faced by society. The contributions scientists and pharmaceutical companies have made to the health of society is enormous, and I don't know a single person who has not benefited from them. And yes, they and I will expect them to make a profit regardless of who the stake holders may be. (No, I do not have any ties to anyone)
Yet if we as a society want to combat this real issue, remember childhood obesity and diabetes, we must ask ourselves if a 20 mg pravastatin should replace a 20 minute walk.
I hope the answer is no. If it is, then we need to start asking ourselves different questions. I have no doubt they'll be equally troubling to our comfort zones. -
0Votesanswered Apr 14, 2011 at 05:39AMCarolyn,
I welcome debate on issues and ideas. There is no place about personal attacks without any evidence. There has been amalgam of facts and preconceived perceptions. I do not believe that past association with or working in the pharma/biotech industry reflects present situation or mean perpetual COI for rest of life! My current editorial policy is published and has not attracted any funding or sponsorship for over a year! I am pro R&D and in favor of faster approval of new safe, effective and affordable drugs for human diseases for which there are none or limited therapeutic options. Millions of patients all over the world with chronic ailments are waiting and tired of execuses from the industry, regulators, governments, healthcare providers, NGO/charities, politicians about lack of treatment options.I write mainly to share knowledge about new innovative drugs in R&D with my 25000-30000 readers per week from industry, top universities, leading hospitals, financial firms and government agencies.
https://docs.google.com/Doc?docid=0AWvMNxkrqMyxZHZnNGc4dF80MTJocW5renNmcw&hl=en
http://knol.google.com/k/knol-first-second-year-odyssey# -
0Votesanswered Apr 14, 2011 at 12:13PMHere are some extracts from the AAP guidelines
The American Academy of Pediatrics new guidelines on cholesterol screening and treatment recommendations in children with a family history of high cholesterol or premature heart disease a fasting lipid profile is recommended between the ages of 2 and 10 years. Obese children, those with hypertension or diabetes, and those whose family history is unknown should also be screened.
In addition to encouraging a healthy diet and increased exercise, the report recommends cholesterol-reducing drugs for those over 8 years old who have high LDL cholesterol. For younger children, weight reduction, more exercise, and nutritional counselling are recommended. All children above 2 years of age should be encouraged to eat healthily, including low-fat dairy products.
These guidelines are needed in the light of more robust evidence on the early development of atherosclerosis, the effect of abnormal lipid profiles, wider availability of treatments, and an increasingly obese childhood population. But the recommendations are controversial, not least because of the paucity of long-term efficacy or safety data for children treated with statins or other cholesterol-lowering drugs.
A third of all children are now overweight or obese in the US. A cultural shift must take place to promote affordable diets rich in fruit and vegetables, and low in saturated fats and refined sugars—at home and at school, banning junk-food advertisements to children and incorporating more physical activities into everyday life have to become the norm. But for those children who remain at high cardiovascular risk, adding cholesterol-lowering drugs to their diet and exercise regimens could be a necessary step.
Daniels SR, Greer FR; Committee on Nutrition.. Lipid screening and cardiovascular health in childhood. Pediatrics. 2008 Jul;122(1):198-208.
Avis HJ, Vissers MN, Wijburg FA, Kastelein JJ, Hutten BA. The use of lipid-lowering drug therapy in children and adolescents. Curr Opin Investig Drugs. 2009 Mar;10(3):224-31.
Comment in:
• Pediatrics. 2008 Oct;122(4):904-5; author reply 906-7.
• Pediatrics. 2008 Dec;122(6):1406-8; author reply 1408. -
1Votesanswered Apr 14, 2011 at 04:16PMKrishan, it appears that you haven't found any revision of the AAP policy regarding the lifelong use of statins in children 8 or older since the 2008 writing. However, I found an interesting article in the online Consumer Reports Health http://www.consumerreports.org/health/best-buy-drugs/statins-in-children/overview/index.htm from June 2010 which clearly casts worry on, what appears to me, to be an ad hoc ( little or no evidence basis) decision for pediatricians to use statins off-label on children who do not meet the strict FDA diagnosis for use which would be for "an inherited cholesterol condition, heterozygous familial hypercholesterolemia, that causes very high levels of LDL in the blood—along the lines of over 500 mg/dL, leading to artery damage and possibly heart attacks at a relatively young age."
The article concludes with "There is also concern over the long-term potential risk for children and adolescents who use these medications for years or decades, particularly the effects on the developing central nervous system, hormone levels, immune function, and organs. Lipids play a role in brain development, and at least two statins, simvastatin (Zocor and generics) and lovastatin (Altoprev, Mevacor, and generics) can cross the blood-brain barrier and could have a direct and negative impact on such development, according to a recent editorial in the Canadian Medical Association Journal.
It appears that many of the studies that have been done on children who have inherited high cholesterol levels are short-term, whereas statin therapy, in any case, may be a lifetime drug."
What do you think? ..Maurice. -
0Votesanswered Apr 15, 2011 at 10:02AMMaurice,
Thanks for your comments and new links with recent updates.
CDC data estimate that 17% of children (9.5 million) aged 2-19 years in the US are obese. Contributory factors are single parent, low income, minority community, chronic condition, lack of health insurance, junk food and lack of physical activity. According to the ASHP, 2.3 million prescriptions were written for statins use in children. For Lipitor 51 million prescriptions were written in the US (IMS data). Lipitor and now Crestor have been used long term (for several years) in children with the rare genetic condition Familial hypercholesterolemia which causes very high levels of LDL cholesterol. However the number of such children is small and may be few hundred only. The single gene mutation occurs in 1 in 500 and the double mutation 1 in million births. Thus in the US, there may be 200000 and in Europe 300000 children at risk with genetic disposition to high cholesterol. These children may benefit from statin therapy.
A large pan European public health EUREKA study in 7000 patients in 12 countries funded by Astra Zeneca but managed by independent academic panel. The EURIKA study suggests that out of 4.3 million CV deaths in Europe, 135000 lives could be saved by control of CV risk factors hypertension, cholesterol, smoking and diabetes.
Trials in children are problematic and raise moral and ethical issues. The research driven innovative pharmaceutical industry may not be interested in following this indication due to ethical, liability, cost, risk and low return on investment issues. As most of the statins except Crestor are generic or going to be generic, there is no incentive for big pharma to do long term risky trials with uncertain outcome. Generic companies are rarely invest in long term clinical studies. The long term data can be generated by the NIH or its institutes (NHLBI, NICHD, NIDDK) only. Generic statins crossing blood brain barrier can be excluded from use in younger age groups. -
0Votesanswered Apr 16, 2011 at 10:05AMAll statins drugs like pravastatin, simvastatin, lovastatin and currently atorvastatin had 6 months additional patent life for branded drugs. This was done after development of formulations and data for pediatric use. I assume that there is implied FDA approval for use in high risk children (includes obesity). I am not sure if it off label? In addition, retrospective case study analysis of health insurance data or the FDA MedWatch can provide information about the long term use of statin drugs in children vs a control group without statin.
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The content on or accessible through Medpedia.com is for informational purposes only. Medpedia is not a substitute for professional advice or expert medical services from a qualified health professional.
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Where is this "push from many quarters" in favour of new drugs to treat childhood obesity? Really? Which quarters?