I've blogged on the subject of research integrity and conflicts of interest by researchers and research funders -- whether they be pharmaceutical companies or government health agencies. This past week, Dr. David A. Shaywitz, an endocrinologist at Mass General Hospital, weighed in with a helpful op ed piece in the Boston Globe. Said Shaywitz: "The quaint notion that university researchers operate on a higher moral plane than business people might be charming if the implications weren't so profound: attention-getting results can lead directly to employment, promotion, and prizes, all leading to personal gain. Not surprisingly, some of the most notorious perpetrators of research misconduct have been academic investigators with no company relationships." Shaywitz doesn't offer the funding source for those "with no company relationships," but it seems clear: government agencies.

Shaywitz concludes sagely:

Coming up with novel treatments for dreadful diseases is a difficult enough task under the best of circumstances; let's not complicate this mission further by misjudging either the intrinsic virtue of academic scientists or the alleged venality of drug companies; instead let us learn how to foster productive, transparent collaborations so that the promise of modern science can be realized inthe treatment of our patients.

Nice touch, ending with a call for a health outcomes focus.

FDA announced today it will act to safeguard the integrity of its advisory commitee process "to provide greater clarity and transparency in the disclosure of waivers of relationships that could present the appearance of conflicts of interest."

Recognizing that important expertise lies outside the realm of government scientists, agencies with scientific policymaking roles (HHS, EPA, DOL, etc.) routinely employ outside advisory panels. With appropriate safeguards they well serve the public interest.

The FDA news release continues:

"The advisory committee process is integral to examining the intersection between medical practice and clinical research, to spark debate about it, and to subject scientific work to close public scrutiny," said Dr. Scott Gottlieb, FDA's Deputy Commissioner for Medical and Scientific Affairs. "Some of the most valuable input often comes from people who are active practitioners but also heavily engaged in clinical research and we need to make sure that we continue to have the ability to recruit top clinical trialists."

FDA believes it is crucial that the public have complete confidence in the integrity of the advisory committee process. Therefore, in the next few months, the agency plans to take the following steps to help ensure that our advisory committees continue to be scientifically expert and independent and that the advisory committee process is transparent:

Issue a guidance identifying more clearly the conditions under which conflict of interest waivers are granted. Currently, for example, waivers can be granted to committee members under certain circumstances for participation in scientific endeavors related to the work of the committee, as well as for certain unrelated activities. Issue a guidance specifying when waivers of conflict of interest will be disclosed to the public and what information will be made available.

Issue a guidance specifying when briefing materials used at advisory committee meetings will be made publicly available.

Provide greater public dissemination of advisory committee schedules through increased mailings to public groups, and providing electronic notifications through an FDA advisory committee list serve and posting on the FDA web site.

Implementation of a more streamlined approach to the appointment of members to the agency's drug-related advisory committees.

Unfortunately, the plan has an enormous blind spot. As we observed a couple weeks ago when the Journal of the American Medical Association also sought to preserve its integrity:

JAMA's new rules are fundamentally flawed. They limit consideration of financial conflicts of interest to those with funding ties to private industry, totally ignoring the fact that many researchers sustain their professional careers fulfilling the agendas of government health agencies. Major studies can bring in nine-figure grants or contracts and lead to career-enhancing publications, professional visibility -- and more grants. Public health agencies have their own special interests, including promoting favored public health strategies. These are not disclosed and rarely considered. But they're real.

FDA would do well to introduce transparency and safeguards into the process by ensuring that its advisors' funding ties to the Agency itself and to other government funding sources be fully disclosed as well as those to private industry. Whether the dollar is provided by a taxpaying, for-profit organization, a tax-exempt "public interest" organization or a tax-funded agency, we need to recognize that these institutions all have agendas and bias. Full disclosure and rigorous attention to research quality will be required.

CBS News correspondent Andy Rooney has a way of speaking for the common man. Yesterday, "60 Minutes" revisited a 1996 commentary where Rooney complains about the difficulty consumers like him would have choosing a low-sodium diet. You can read the transcript or watch a video clip of "Diet Guidelines Get Andy Salty " online.

Presumably, Rooney is supported by a research staff that should protect him from such gaffes as equating salt and sodium. Instead, this "common man" highlights that ignorance, suggesting that he feels normal consumers have a hard time with the distinction (yes, Andy, they are different; about 40% of salt -- sodium chloride -- is sodium and the other 60% chloride). Interesting. He concludes, observing that the American Heart Association advises against more than one stalk of celery n a pot of stew; "the other day at a party I ate two stalks of celery so, if I'm not on next week because I dropped dead, blame that second stalk of celery."

Respect for authority, of course, doesn't lead to compelling, humorous commentary, so there are likely many who share Rooney's disdain for such dietary strictures. Where needed, then, the credibility of advice to reduce dietary sodium is undermined because of the over-reaching, picayune nannying delivery of what may be life-saving advice.

Whether the advice is life-saving is the real question. Difficult as it may be to effectuate a low-sodium diet, the real question is the other side of the equation: why reduce sodium in the first place? Most Americans consume a moderate sodium diet (3,500 mg sodium, right in the middle of the global average and about midway in the 2,300 - 4,600 "hygienic safety range" identified by Swedish expert Dr. Bjorn Folkow). All studies of the health consequences of reducing dietary sodium fail to identify any population benefit for Americans; some find additional risk.

So, Andy, before you dust off that commentary for a third re-run, we suggest you change your focus and lament that this nutritional advice is not only unpalatable, it is likely unnecessary -- and join the Salt Institute in its call for a controlled trial of the health consequences of reducing dietary salt - or sodium.

"Sodium: the missing link" is timely advice for ulta-endurance Ironman competitors, but it contains useful information about the importance of sodium (salt) to a healthfully-functioning body. RaceAthlete.com has this advice:

Sweat rate, genetics, fitness level and acclimatization will affect the amount of sodium lost during a race. A well-conditioned, heat acclimatized athlete would lose about 920-1840 mg per liter of sweat per hour of racing. If you can get an idea of your personal sweat rates, a good place to start with Na supplementation would be in the middle of that range. For example, if the average sweat rate is = 1.5 liters per hour, about 1380 mg Na per liter = 2070 mg Na (about 2 grams) is lost per hour.

We are making assumptions since we can never really know how much sodium a person looses unless tested. For instance, another elite Australian Ironman triathlete went to the Gatorade Sports Institute to determine his Na needs. Through testing, they found he needed 3,000 mg per hour! This demonstrates the wide range of Na intake between individuals.

With hot summer weather here and still ahead, this advice could make your outdoor exercise enjoyable or even save your life.

The U.S. Food and Drug Administration is always between a rock and a hard place. Consumers want the latest and best drugs NOW and they want them thoroughly tested for safety and effectiveness, a process that takes years.

Seeking to introduce efficiencies into the process of conducting the trials to speed them up and lower costs that are passed along to consumers, FDA's deputy commissioner Scott Gottlieb has announced plans to develop guidelines for "adaptive trials." An "adaptive trial" would allow a very different model from the classic scientific testing where the hypothesis is clearly stated at the outset and "post-hoc" adjustments are greeted with great skepticism or rejected automatically. Only an ethical or safety issue would adjust, or more likely, terminate, a clinical trial under the current rules.

Nobody can be for long and costly trials, but "trials" are what they are: not the real thing. If we shortcut the careful and objective science, already compromised by hidden agendas of funding agencies or researchers out to bolster their credentials and their careers, we risk undermining the credibility of our regulatory watchdog. This will bear careful watching.

For example, if the new rules were to apply to non-pharmacolgic investigations as well as trials of new drugs, the reported conclusions of the massive, to-be-definitive Intersalt Study back in 1998 would have been far different. The primary hypothesis was stated that evidence would show that sodium excretion (salt intake) was directly related to population systolic blood pressure. The secondary hypothesis was that sodium excretion (salt intake) was directly related to population diastolic blood pressure. The evidence did NOT confirm these hypotheses, but the reseachers wanted to conclude that salt was problematic so they performed a cohort analysis and constructed a new hypothesis of "blood pressure rise with age" (also subsequently debunked).

Another example, the federal government conducted its Trials of Hypetension Prevention Part II and found that in the first six months, systolic blood pressure fell sharply by about 6-7 mmHg from 127.7 mmHg. It issued news releases and has continued to tout this result for years. But the trial was a 36-month trial and, although sodium intakes remained 920 milligrams below baseline after 36 months after initally declining by 1,150 mg, blood pressure regressed back to its high "normal" of 127.1 mmHg, a statistically insignificant change -- so insigificant that the government sponsors decided to ignore it and use only the 6 months figures which did find the "correct" change.

If the government cooks the books under the current, more rigorous rules, we need to put into place additional guidelines to restore the credibility of its analyses, not further erode the process and our confidence in its conclusions.

Cornell University researchers have discovered why gorillas eat rotting wood: for the salt. Remote areas often lack sufficient salt for their human and animal denizens and, recognizing that salt is an essential nutrient to survival, all species go to often-disgusting extremes to get the salt they need. The research will be published shortly by the Royal Society of Biology, according to a Fox News report July 10th.

This week's Journal of the American Medical Association included an editorial by editor-in-chief Dr. Catherine D. DeAngelis announcing the prestigious journal's tightening of its conflict-of-interest policy in response to scientists' failure to disclose all financial ties to pharmaceutical companies. Said DeAngelis:

Authors are expected to provide detailed information about all relevant financial interests and relationships or financial conflicts within the past 5 years and for the foreseeable future (eg, employment/affiliation, grants or funding, consultancies, honoraria, stock ownership or options, expert testimony,royalties, or patents filed, received, or pending), particularly those present at the time the research was conductedand through publication, as well as other financial interests (such as patent applications in preparation) that represent potential future financial gain.

Avoiding conflicts of interest is obviously a good thing and disclosure of funding relationships is certainly important in that regard. But JAMA's new rules don't get the job done.

JAMA's new rules are fundamentally flawed. They limit consideration of financial conflicts of interest to those with funding ties to private industry, totally ignoring the fact that many researchers sustain their professional careers fulfilling the agendas of government health agencies. Major studies can bring in nine-figure grants or contracts and lead to career-enhancing publications, professional visibility -- and more grants. Public health agencies have their favored strategies and their own special interests. JAMA would do well to have these conflicts disclosed too.

Harvard professor Thomas Stossel made much the same point in an op ed in the Washington Post July 2nd where he pointed out that journal editors play favorites, imposing (entirely appropriate) rigorous peer-review standards on academic researchers while exempting public interest groups from such scrutiny despite the fact that they often receive grants from parties at interest too.