The Personal Paradigm and Peer Review

RenalWeek 2009 in San Diego is underway. I just enjoyed a forum on conflict of interest in medicine. One talk, by Rober M. Califf, MD, of Duke University, discussed bias in clinical trial reporting. Most of the speakers focused on financial conflicts of interest. Dr. Califf described a number of nonmonetary conflicts of interest as well.

One of these nonfinancial conflicts involved scientific hubris. For example, you review a paper or a grant and its (potential) results shoot down your own research and ideas. Do you accept the possibility that you are wrong? This work has the potential to make your prior work irrelevant, as well as decreasing your ability to get funding and promotion. The document is well-written and convincing, at least to the other reviewers. Do you allow it to proceed, or do you demand further work to reconcile it with your current hypothesis? Data that may not be feasible, if your personal paradigm is wrong?

We scientific types supposedly worship at the alter of truth and knowledge. We are human, though, and humans like to have explanations for everything. As nature abhors a vacuum, our brains hate missing information or pieces. In other words, we are biologically predisposed to develop hypotheses and patterns for everything around us. We also seem predisposed to defending views in which we are invested.

This source of conflict is rampant in peer review. Qualified peers must have knowledge of the subject area in question, and they will have pre-formed hypotheses about the material. Most reviewers can accept new experiments that advance their ideas, even if the world moves in a new direction. When those pre-formed ideas quash legitimate questions, then they become a source of conflict of interest.

What can one do? One can exclude reviewers based on probable bias. This practice is commonplace for manuscript submission. If a member of your study section could be trouble, you can request that they not review your grant. You should send your stuff to lots of different funding agencies as well; the same proposal may be funded by one agency and triaged by another, just because peer review is subjective and biased in this way.

Human nature simply will not allow all sources of bias to be removed from the world. I hope we in science can consider our own intellectual prejudices and overcome this conflict of interest.

Photos courtesy of PhotoXpress.

Greetings From San Diego

Most of my administrative tasks have now been completed. I am sitting in a session on conflict of interest, especially the infiltration of pharma into professional societies.
More on this later (when I have my netbook rather than my iPod). Just wanted to let everyone know I was alive!

On The Road Again

Tomorrow I hit the airport en route to Renal Week, the Annual Meeting of the American Society of Nephrology. After some administrative work, my week will be devoted to all things kidney. From the most basic science to the most novel clinical trial, 14,000 devotees of urine (or lack thereof) will be gathered to celebrate their favorite organ.

Attendees and other kidney fans are invited to Tweet the Week. We will be twittering about the meeting and other events surrounding it. I am sure Renal Week will provide fodder for this august venue as well.

I will also try to update everyone on the weather. After all, I will be in San Diego. I get to gloat at those I leave behind in Nebraksa.

A new podcast should also be available soon. I chat with current president Tom Coffman and president-elect Sharon Anderson about the ASN. Look for it and other meeting stuff on the site or in our iTunes area.

For the rest of the day, well, my brain has already flown west…

Correcting My Mistake

Back in August I bought a pair of black shoes. The heels were just under 2 inches on a study wedge. Embossed leather resembled croc. Great meeting and work shoes; dressy, but grounded enough to walk in all day long.

Unfortunately, they eat my feet. Blisters and cuts and pain, Oh My!

Yesterday I acquired the Steve Maddens shown in the photo. They are far more stylish with the patent ruffle. Most importantly, they do not damage my feet.

And I only paid $35.99 at DSW.

Of course, I would wear something totally hot if I were presenting a plenary. I saw these Steve Madden’s in a department store yesterday. I could not figure out a reason to buy them. At least not until they go on sale. You have to admit, they make a statement.

For more shoe wars, point your browser on over to Isis’ place. Hot (and not-so-hot) shoes are driving debate between the bloggers. Don’t miss out!

True Confessions

Over on Isis the Scientist, a perfect storm developed about one of Intel’s recent ads. The ad, depending on one’s viewpoint, might suggest that physical exercise and mental exercise are mutually exclusive and/or that women can’t play chess, the mental work-out.

I am a woman with a high aptitude in math and science. I test at the top of the scale on pattern recognition and manipulation, especially in three dimensions. That test where they show you the paper pattern and you have to figure out what object they would become when folded? Piece of cake. When I did Now, Discover Your Strengths, “Strategic” is number 1.

So why can’t I play chess?

I came of age when Bobby Fischer was kicking Russian ass. Kids my age were chess geeks, and it was not a bad thing at that time. I learned how to play, but I never got good.

Truth? I found chess boring. Incredibly, colossally boring.

Today, I feel the same way about sudoku. I love crossword puzzles and word searches. My new BlackBerry Tour came with Word Mole; it is a blast! But those number patterns? Who the hell cares?

Of course, while we’re at it, I guess I should confess that I lied at my medical school interviews. I told everyone I was interested in a primary care career in a rural area. It was the reason my school existed, and I knew it would be a + in a column for my application. Of course, the one thing I was not considering was a career in pediatrics. Yet, here I am today, a Pediatric Nephrologist.

I feel better now. I still can’t beat you at chess. But then, who the hell cares?

Photo courtesy of PhotoXpress.

Moving On & Moving In

A couple of months ago our cat of 18 years, Denver, died of chronic kidney disease (yes, I know, it is ironic since I am a nephrologist).

My husband never wanted a cat. He tried to convince our almost 4 year old daughter that she wanted a puppy. Her highness was not amused, and we adopted The D from the local animal shelter on her birthday.

My husband, the dog guy, decided last week that we had been feline-free long enough. He missed a buddy with whom he could play, watch TV, curl up with a good book, or nap. So last weekend we found ourselves at a shelter outpost.

And now I am introducing Ozzie:

This 2 month old guy (who would fit in one hand) was found at an intersection in town. He had a cold when we got him, and he didn’t eat last Sunday. After a trip to the vet for fluids, and some higher calorie prescription food, he is the joy and the terror of our lives. He is inhaling canned and dry food. He likes to be chased. He would love to someday catch the laser pointer dot.

He thinks my laptop is a really big cat toy. Writing this post challenged me, both to get it done and to keep him from “writing” his own contribution.

It took several days to name the little beast. Ozzie was selected because it is the name of a Hall of Fame Cardinal shortstop, and short for Osiris of Eyptian lore (hey, they worshipped cats).

He has no pedigree or papers. His origination is “46th and Curtis.” Yet we know he is the greatest cat in the world. Next to Denver.

The Problem With Peer Review

"If this is the best of all possible worlds, what are the others?"

- Voltaire, Candide, Chapter 6

Peer review is a lousy way to score research proposals; it just seems to be the best one we have found to date. NIH is altering its application and review processes, attempting to improve things. Unfortunately, the major problem cannot be fixed.

What major problem? The peer reviewers.

For example (derived from my own experience and that of my colleagues):

A proposal is submitted to study biological process A in disease X. A model of disease X is proposed, and standard techniques will be used to examine the role of process A. On initial submission, the reviewers say that process A appears to be important in disease X, but “enthusiasm would be stronger” if further preliminary data were presented. Furthermore, pathway Y contributes to process A, so perhaps it should be included in the study.

As PI, you consider these suggestions and do further experiments to augment your preliminary data. You review studies of pathway Y and conclude that it should be included in your proposal. You rewrite you grant, and send it back to Bethesda.

This time, you have a novel reviewer. Those who saw the first version are satisfied, but the latest one feels that biological process B is of far more importance than process A, even though you have data and published literature from other labs supporting process A. Perhaps the latest reviewer believes you should study disease Z rather than disease X. Or maybe a different model should be used, even though you have been using this model for all other work in your lab. Or, perhaps, s/he wants all of the above changed.

By the way, the reviewers also criticize your productivity because, while generating the preliminary data requested, you have not continued to publish as many peer-reviewed journal articles.

This wackalunacy must stop.

It is one thing to suggest additional experiments or a better technique. These suggestions may strengthen the work.

Telling the PI to completely change the nature of the study is inappropriate:

• Look at process B even though your preliminary data and published studies support process A in your hypothesis
• Disease Z is more important than disease X, even though you have never studied disease Z

Proposals get toasted with this sort of criticism in each round of reviews. If we could fund the top 25-30% of proposals(which are getting scored in the very good-excellent range), some of these applications would still fly; in the current funding drought, any little glitch (no matter how trivial) can drop the score below the pay line.

I do not have the answer. I beg any reviewers reading this to play fair. Judge what is proposed; no study can examine every biological process! If your favorite pathway is omitted, fear not! Someone else may be asking that question; let this PI examine his/her idea! Occasionally I have seen someone who proposes to examine the role of process A in disease X, but is using a model of disease Z. This is a major flaw, and a change of model or disease is in order. It is NOT in order if you, the reviewer, find disease Z more interesting than disease X. Would you want someone to tell you to study disease X? I thought not…

NIH has shortened its application process and changed the scoring system. Somehow I don’t believe this will change reviewer behavior, but I will find out early in 2010.

In the meantime, I will just keep imagining worse worlds of review. I finally appreciate Candide.

Art courtesy of PhotoXpress.

Healthcare for all?

Denver, our cat, died of chronic kidney disease a few months ago after 18 years of life with our family. He required extra care, medications, and a special diet for the last 2 years of his life, and it cost $1-2 per day to keep him going. He was happy and interactive until his last day, and the expense was worthwhile.

My daughter has been generally healthy, but she does have a couple of “pre-existing conditions” that might prevent her from getting health insurance. We hope she will find a job with good group coverage, or that reforms pass that will allow her to be covered.

While the healthcare debate mires in political mud, Representative Thadeus McCotter of Michigan has proposed the Humanity and Pets Partnered Through the Years (HAPPY) act. The bill would give pet owners a tax deduction of up to $3500 annually for the care of their animal companions. (For a detailed news story, click here)

Based on covereage of the proposal, its primary aim is economic stimulus. As McCotter told DoggyTV:

Anything that puts cash back in Americans' hands during the economic crisis is a good thing.

All well and good, but exploring the congressman’s web site reveals that this republican does not believe the current stimulus package is beneficial. So why would a pet owner tax deduction be more stimulating? I mean, I would love to deduct my pet expenses for the year, but, frankly, it was a luxury to keep a sick, geriatric pet alive.

I then explored his comments on the Obama healthcare proposal, and they confuse me. His statements suggest that our “system” is not in crisis, nor is reform required. I thought the Big 3 Auto Makers were behind reform! Don’t they still count in Michigan politics?

I hope congress lets this bill drift away. Don’t get me wrong; I love my pets, but my daughter’s health and insurability is far more important to me. I think we should guarantee coverage for every US citizen before we think about reducing taxes for pet owners.

HAPPY won’t make me that way.

What I'm Reading

It's been a while since I shared my pleasure reading. Last weekend I began The Crime Writer after my dad passed along a copy. It only took a couple of days to finish it, and I recommend it highly.

The protagonist, a successful crime novelist, awakens in a hospital room. He was found seizing, holding the knife that killed his ex-fiance, lying across her corpse. Ultimately found guilty of the crime, he is freed because of the benign brain tumor that could have induced temporary insanity, as well as the seizures.

He gets home, and has bizarre "dreams" complicated by unexplained injuries. To determine if he is sleepwalking, he sets up a webcam to record his sleep. This comes in handy the second night, when a young woman is found dead with injuries virtually identical to his ex-fiance.

He responds by doing that which he has always done: writing. As he assembles the story he is living, his research brings him to the real killer(s). Of course.

Mysteries enthrall me; I can't get enough of them, and I almost always uncover the key plot elements before the detective. This novel accomplished a rare feat: I did not figure out who the real killer(s) was/were until the same moment the protagonist did. That alone makes it an amazing read. The book is sprinkled with interesting facts and technical details, as well as one key plot twist, but it won't hurt your brain.

My patients have occupied me fully for the last 5 days, but I should find time to open something new this weekend. Keep on reading!

A Little Bird Told Me…

In late September, the football coach at Texas Tech outlawed Twitter for his team, as reported by ESPN:

Coach Mike Leach said Monday he has banned his players from using Twitter after one of his linebackers noted the coach's tardiness to a team meeting in a tweet Sunday, one day after the Red Raiders lost 29-28 at No. 12 Houston.

Now, publicly criticizing your coach for being late is not a wise idea, especially after a close loss. Marlon Williams, the linebacker in question, has learned an important life lesson. However, Leach goes on to make it clear that he just doesn’t get Twitter:

"I think that a guy who plays college football gets enough attention," he said. It's "a bunch of narcissists that want to sit and type stuff about themselves all the time. We'll put mirrors in some of their lockers if that's necessary but they don't have to Twitter."

Before I began tweeting, I wondered why people wanted to know what I was doing. It did seem silly and narcissistic, but then I signed up. Twitter isn’t really about what I am doing; it’s about pointing people to interesting things I have found on the web. It’s about spreading the word for an online petition or a fundraising event. It is about what my friends have found. It is just another form of communication, like the phone or email or texting.

Today one of our medical librarians sent me a link to a posting with 140 ways Twitter might be used in healthcare. We have already seen its power in political events, like the Iranian “elections” earlier this year.

The coach at University of Texas, Mack Brown, takes a different approach to Twitter and other social media, since he believes banning its use could be illegal:

"It would be a football rule and when they're students away from us, they really are under the guise of the university more than football," Brown said. "What we have done is encouraged them not to be on it. If they are on it, then they need to be classy and not put anything on there that they don't want their mom to read. These kids think that they're just in conversation with buddies, and that's public information."

Brown said he encourages Longhorns players to step back and think about the ramifications of what they post -- not just now, but in the future.

University of Missouri has promoted tweeting by Sean Weatherspoon, a senior starter. His tweets have not revealed any team secrets or inappropriate information, but they do give us a peek into the life of the college athlete.

Twitter can be used in many ways, and I have been surprised by its usefulness and entertainment value. Of course, I would never tweet if my boss were late to a meeting; I have learned something in my 48 years on the planet. I bet Texas Tech linebacker Marlon Williams never does again, either.

All quotes are from the coverage by ESPN.

Unbelievable!

I’m watching a show on TLC that I have never seen before:

I Didn’t Know I Was Pregnant!

Now, as a physician I have seen a few women who denied being pregnant while in active labor; these were generally teens who denied ever having sex. They were clearly in deep, deep denial.

The women on this show are different. Most are older. Some have had prior pregnancies. Most took urine pregnancy tests that were negative. So why didn’t these women seek medical attention? One had irregular periods and all sorts of pain and fatigue. One developed breast discharge, yet still didn’t seek medical attention.

I guess I can believe that there are this many women who make it to term without knowing they are pregnant. I just can’t believe it’s a TV series.

Image courtesy of PhotoXpress.

Philanthropy Begins With Me

The local United Way campaign just kicked off, and the folks over on ScienceBlogs started up their Donors Choose program (click on over and help Isis win). As the leaves fall, so should dollars into important programs.

I decided to become a philanthropist shortly after taking my first faculty position in 1991. The funding climate, similar to today, was brutal for a new PI. I knew my best chances were with private foundations, especially local groups. So there was some self-interest in my initial volunteer efforts; however, I figured that it was my job to enable biomedical research, even if I never saw a dime.

Eventually, I did get some of that money, and it led to bigger and better grants. I still believe in keeping up the efforts. In the current economic climate, those same organizations and foundations are the only source of funding for many new investigators or for those whose idea isn’t quite ready for prime time (the NIH).

That’s why I am giving to enrich elementary science programs. That’s why I dragged my butt out of bed on a cold, soggy morning yesterday to volunteer at the local American Diabetes Association Walk (the balloon release at left kicked it off). That’s why I made time Friday to do a promotional interview about the Nebraska Kidney Association. This stuff is important, both now and tomorrow.

So click on over and support tomorrow’s scientists at ScienceBlogs.

Cylinder artwork courtesy of PhotoXpress.