From funding to findings

Times Staff Writer

From the time that a drug is little more than a promising compound until well into its commercial life span, medical researchers, academic authorities and influential specialists are key players in its commercial viability.

Drug companies regularly enter into commercial partnerships with universities, endow academic programs and teaching chairs, and pay academic medical centers to run clinical trials. In doing so, they build a corps of respected university experts who have lengthy experience with a drug prospect, financial ties to the firm that paid them to study it and, often, a direct stake in its success. These university-based physicians enjoy a public perception of scholarly impartiality as well, which can make them influential voices when they speak in favor of a medication or treatment.

In 2 1/2 decades, drug companies’ funding of biomedical research -- much of it conducted at universities -- has risen from $1.5 billion to $55 billion. In the United States, pharmaceutical investment in biomedical research has outpaced and, ultimately, overtaken the federal government’s investment in such research, expected this year to be about $36 billion. The university-based researchers and physicians who conduct this work often serve on or testify before committees that advise the Food and Drug Administration on drug approvals. They then play a vital role in building markets for new and existing prescription medications -- this time by serving on expert committees that write treatment guidelines and standards. These “clinical practice guidelines” enshrine the medical profession’s consensus about which patients should be treated for certain conditions, and how. Drug company marketing departments prize these recognized authorities as “opinion leaders” and cultivate them accordingly.


A New England Journal of Medicine article in April surveying relationships between physicians and pharmaceutical companies found, for instance, that developers of clinical guidelines were 41% more likely to have received payments from drug companies for consulting, lecturing or trial recruitment than physicians not involved in guideline development. Physicians teaching at medical schools were 67% more likely to have received such payments than those who did not teach.

The power that clinical guidelines hold to expand the market for a drug is immense.

In May 2003, for instance, a government-sanctioned panel of experts revised the definition of which patients should receive prescription medication to control high blood pressure. Overnight, the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure expanded the market for blood pressure drugs by millions of new patients. Nine of the 11 authors of the report had financial ties to companies likely to benefit from the new guidelines. Six had conducted research under grants provided by one or more of the four pharmaceutical giants that held patents on prescription drugs used to treat high blood pressure.


Wider market for statins

In July 2004, the National Cholesterol Education Program conducted a similar revision of the clinical guidelines for diagnosing and treating high cholesterol in adults. With the new guidelines’ publication, 8 million Americans became candidates for cholesterol-lowering drugs -- three years after an earlier guideline had added 23 million to the potential rolls. Most of the committee members were subsequently found to have had extensive ties to companies that make statins, widely used in the treatment of high cholesterol.

Guidelines like these are clearly saving many lives. But they also have made Americans with elevated blood pressure the most aggressively medicated patients in the world. A January study in the Archives of Internal Medicine found that 64% of patients diagnosed with hypertension in the United States were getting two classes of drugs to treat the condition -- compared with 59% of British and German patients with high blood pressure and 49% in Spain.

The guidelines also have made statins -- led by Pfizer’s Lipitor -- the world’s bestselling prescription medications, despite growing questions about their appropriateness for many users. The 1994 edition of the psychiatry profession’s single most influential guideline, the Diagnostic and Statistical Manual of Mental Disorders, was recently found to have been written by a panel of experts among whom 56% had at least one financial relationship with a pharmaceutical manufacturer. For experts writing guidelines for severe mental illness such as bipolar disorder and schizophrenia -- diagnoses that have been broadened significantly in recent years -- 100% had ties to drugmakers, according to the study, which was published in Psychotherapy and Psychosomatics.

“At present, the financial ties between the guidelines panels and industry are extensive,” wrote Dr. Robert Steinbrook in the Jan. 25 issue of the NEJM.