Alex O'Meara » cancer

Redefining clinical trials out of existence

Alex — Fri, 24 Sep 2010 17:56:04 +0000

I was flying home to Arizona from Charlottesville, VA when I read the story in the New York Times, New Drugs Stir Debate on Rules of Clinical Trials, about a controversy over using a trials drug to treat cancer patients. I had been in Charlottesville for my yearly overnight checkup as part of a clinical trial to cure diabetes. I had received an infusion of islet cells four years earlier and each year I returned to the University of Virginia and they ran more tests than they would on an astronaut. By the time I got on my plane my arms were black and blue, I had not slept in 36 hours, my blood sugar had spiked over 500 as part of the testing and I had nine hours of flying to get through before I could lay down at home.

That’s was partly why when I read in the NYT article that some cancer experts thought a new wave of experimental cancer drugs should be used for treatment before they’re approved I sat stunned. I read the article three times. “Experts” are actually arguing that patients should have increased access to drugs not yet tested and that this should be done on compassionate grounds. This article, by the way, came out a few days before the FDA decided to restrict Avandia, a drug that HAD ALREADY BEEN APPROVED because it increased the likelihood of heart attack

The very first time I saw the words “therapeutic misconception” in the New York Times was just one month ago. In an article by Gina Kolata, What to Tell the Patient After a Trial Goes Awry. “Most patients entering clinical trials believe they are getting a new treatment that may benefit them, Dr. Brody [director of the Center for Medical Ethics and Health Policy at Baylor College of Medicine said]said. Ethicists call that a ‘therapeutic misconception,’ he said, adding, ‘No one should ever assume that in a clinical trial.”

Gosh, ya think?

Like most media outlets, the Times treats trials as another medical option available to patients. This is because patients consider trials a medical option; as if they’re getting to buy wholesale rather than retail. That’s because doctors and researchers encourage patients to think of them as an option so they can recruit subjects to trials. It’s one vast belief but it’s not true. It’s built on statistics: If enough people believe it, eventually it’s true. I used to believe that truth was not statistical, that popularity didn’t make a thing real. And, of course, in an activity as rigorous about process and facts as medical research, truth was surely an inflexible concept. But after reading the NYT article I realized some researchers want the truth to be flexible, based on the whims of doctors and patients. And that’s a great way to make the truth disappear.

Kids and Oncology Trials

Alex — Fri, 14 May 2010 19:13:00 +0000

This is worth reading. It’s about how kids often don’t understand enough about clinical trials and that can impact how many kids take part in trials. This is especially relevant because pediatric oncology trials have long been hailed as an example of the positive power of clinical trials in developing new treatments quickly and safely to such an extent that lives have been saved.

Kids in CA Trials Lack Understanding of Research

By Todd Neale, Staff Writer, MedPage Today
Published: March 29, 2010
Reviewed by Zalman S. Agus, MD; Emeritus Professor
University of Pennsylvania School of Medicine and
Dorothy Caputo, MA, RN, BC-ADM, CDE, Nurse Planner

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Among children participating in oncology trials, 41% said they did not know specific purpose of the study, Yoram Unguru, MD, of Herman and Walter Samuelson Children’s Hospital at Sinai in Baltimore, and colleagues reported in the April issue of Pediatrics.

Of those who said they did know the purpose of the study, only 22% correctly defined it.

In addition, about half of the children (49%) felt like they had little, very little, or no role in the decision to take part in the trial, despite signing the assent forms.

“Tools to assist investigators ascertain that children understand what they are agreeing to when they assent to research and to determine their preferences for inclusion in research may help make assent more meaningful,” Unguru and colleagues concluded.

The next step, they said, is developing such a tool.

Most children with cancer are enrolled in clinical trials, and the U.S. Department of Health and Human Services requires that children give their assent whenever possible.

However, previous studies of children’s understanding have mainly involved healthy youngsters using hypothetical scenarios, or they focused on decision-making preferences of adolescents, according to the researchers.

To further explore the issue, Unguru and his colleagues interviewed 37 children and teens ages 7 to 19 (mean 13.6) who were taking part in various oncology trials. The researchers used a novel, 69-item quality-of-assent instrument that the children read as they were asked the questions verbally.

The tool assessed familiarity, knowledge, awareness, understanding, and appreciation.

Only about half of the children remembered being told their treatment was research, even though 87% remembered hearing the word “research” and 95% remembered hearing the word “study” from their doctors.

In general, the children had a poor understanding of the purpose of their respective trials, with 70% saying it was a little or very hard to understand information about the trial when they assented.

The vast majority (86%) said they did not understand the language their doctor used.

Most of the children did not understand the nature of their treatment, with 73% saying they thought research interventions were not more risky than other interventions and that the medications they were receiving were proven to be the best for their condition.

Responding to questions meant to assess the children’s appreciation of the goals of research, 73% said they were participating in the trial to help other children, 60% said they were taking part to get better, and 43% said they were helping doctors expand their knowledge.

All of the children said they wanted to have at least some part in deciding to participate in the trial, while 97% said they wanted their parents involved, and 94% said they wanted their doctors involved.

However, about half felt largely excluded from the decision-making process, and 38% did not feel like they could decline to participate, citing pressure from parents, doctors, or both.

“Our findings suggest that parents/physicians could do more to involve children in decision-making to avoid forcing them to enroll in trials,” the researchers wrote.

They acknowledged some limitations of the study, including the small sample, the possibility that the children’s responses reflected what they thought the researchers wanted to hear, the possibility of bias from recalling past events, and the confusion some children had about the difference between clinical care and clinical research.

The authors reported no conflicts of interest.

Primary source: Pediatrics
Source reference:
Unguru Y, et al “The experiences of children enrolled in pediatric oncology research: implications for assent” Pediatrics 2010; DOI: 10.1542/peds.2008-3429.

New York Times Piece About Cancer Clinical Trial Misleading

Alex — Tue, 23 Feb 2010 18:55:34 +0000

I wanted so much to like the piece in the New York Times about a clinical trial on a new melanoma drug that is showing extremely promising results. I still want to like it but in all good faith, I can’t. The story does little more than further promote the false and potentially damaging idea that clinical trials are accepted therapeutic options for treating people who are sick. I feel like I have been saying this by rote forever but it bears repeating: Clinical trials are experimentation and are not meant to function as a viable treatment option. This is a crucial point that Amy Harmon’s article, Target Cancer: After Long Fight, Drug Gives Sudden Reprieve, not only misses but actively contradicts.

The subjects in the trial, for instance, are referred to as “patients,” a term that is misleading and plain wrong for anyone enrolled in a trial. Further, the story of Christopher Nelson and his wife’s desperation to become enrolled in the trial and his subsequent benefits from the experimental drug read more like something out of TV movie than an objective, informative look at how a trial works. Providing cheap drama – complete with a cliffhanger at the end – appears to have been the purpose behind writing the article instead of providing helpful, accurate information. The article will probably have hundreds if not thousands of cancer patients running to their computers and phones to try and get into a trial – any trial – because this article has led them to believe trials can provide a cure. Promoting that kind of false hope is not only bad journalism, it’s just plain mean to patients seeking a cure for cancer.

New Nail in Clinical Trials Integrity Coffin

Alex — Wed, 20 Jan 2010 17:05:59 +0000

The Clinical Journal of Oncology says in a new study that researchers with the greatest influence over cancer clinical trials also have the closest financial ties to the pharmaceutical and other industries that benefit from positive clinical trials’ results. This is a disturbing and alarming finding but, unfortunately, not surprising, The trend in recent years has been for stronger ties between research and corporate interests so this comes as yet one more indication that trials results may be tainted.

The study does not specify the level of attachment between researchers and industry but there are some who insist that even the slightest attachment introduces too much of a possibility of influence over results. Read the article in Reuters here. Other recent news about trials is below:

Insurers agree to cover cancer patients in clinical trials – MiamiHerald.com – Insurance companies will have to continue routine coverage for cancer patients who participate in clinical trials, under a new state agreement. … See all stories on this topic

Wall Street Journal – It is currently undergoing the final stage of clinical studies, or Phase-III trials, in India after successfully completing clinical trials for safety and … See all stories on this topic

Cytokinetics Announces Positive Data From Phase I Clinical Trial of CK-2017357 – CNNMoney.com (press release) – In Part B of this clinical trial, CK-2017357 produced statistically significant, placebo-corrected increases in the force exerted by the tibialis anterior … See all stories on this topic

Clinical Trials Update: Jan. 12, 2010 – BusinessWeek – This study will evaluate the safety and effectiveness of H-coil deep trans-cranial magnetic stimulation for people with major depressive disorder who have … See all stories on this topic

Clinical Trials Update: Jan. 14, 2010 – BusinessWeek – This study will evaluate a new investigational medication. The study involves one screening visit, two in-house stays of five days and four nights … See all stories on this topic

Clinical Trials Update: Jan. 15, 2010 – BusinessWeek – This study seeks candidates aged 18 to 80 with shingles. Those who qualify will receive study medication and related medical exams and tests at no cost. … See all stories on this topic

Clinical Trials Update: Jan. 13, 2010 – BusinessWeek – This study seeks people diagnosed with traumatic brain injury or stroke to participate in a fMRI study on brain activity. The research site is in Menlo Park … See all stories on this topic

Sangamo BioSciences Initiates 2 New Clinical Trials Of ZFP Therapeutics – RTT News

(RTTNews) – Sangamo BioSciences Inc. (SGMO: News ) announced the initiation of two new clinical trials of ZFP Therapeutics, a Phase 2b study in diabetic … See all stories on this topic

Threshold Pharmaceuticals Provides Clinical Development Update at JP Morgan … CNNMoney.com (press release) – The Company has three ongoing phase 1/2 clinical trials of TH-302. The “401 trial” is a trial of TH-302 as monotherapy in patients with advanced solid … See all stories on this topic

Fired Dr. Stratton Blows Whistle on Carle & a Common Practice

Alex — Fri, 23 Oct 2009 21:51:27 +0000

Dr. Suzanne Stratton found that researchers were lax in following the regulations about patient consent for clinical trials at Carle Foundation Hospital, in Urbana, Illinois. As vice president for research she alerted hospital administrators about her concerns late last year. She was fired that same day. Now federal investigators have corroborated many of Dr. Stratton’s suspicions.

The issue of gently or overtly twisting subject’s arms by convincing them that trials exist as a legitimate medical treatment option is not contained at Carle. It is widespread. On pages 49-51 of Chasing Medical Miracles I wrote, “Therapeutic misconception is also a significant issue and is thoroughly built in to how trials function today.” Things don’t get much clearer than that. I only hope that now, with this story about Dr. Stratton in the New York Times today, pehaps people with the power to change this deplorable practice in research will start to listen and change things.

When she arrived at Carle, Dr. Stratton says, she was surprised to find a lax approach to a fundamental principle of clinical research — informed patient consent. Instead, she said, doctors too often promoted trial treatments as superior to standard approaches, even when there was no supporting evidence.

October 23, 2009

Research Uproar at a Cancer Clinic

By DUFF WILSON

URBANA, Ill. — Two years after becoming vice president for research at the biggest hospital in this university town, Suzanne Stratton said she had finally seen enough.

She had clashed repeatedly with a doctor who oversaw the local patients enrolled in more than 130 federally sponsored cancer studies — work that the hospital promoted in local television advertisements but that Dr. Stratton, who has a Ph.D. in molecular biology, said was often putting patients and science at risk.

In a meeting with Carle Foundation Hospital administrators late last year, Dr. Stratton demanded that they take action. She cited an outside audit that had found “major deficiencies” in 12 of 29 experiments being overseen by the doctor she had clashed with, potentially endangering patients or skewing the studies’ results. Dr. Stratton says her bosses responded by firing her, ushering her out of the hospital later that same day.

But federal officials, alerted by Dr. Stratton, have corroborated many of the shortcomings she found. They are continuing to investigate — an inquiry with implications for the nation’s cancer research effort that go far beyond the Carle Cancer Center.

In the last quarter century, among the hundreds of thousands of people around the nation who have enrolled in federally financed trials of cancer drugs and treatments, more than one-third have come through the doors of local medical centers like Carle.

Together, these nearly 400 federally designated community research sites and the network of 3,400 participating physicians amass more evidence for cancer science than at any of the giant cancer centers like Memorial Sloan Kettering in Manhattan or M.D. Andersen in Houston, part of the University of Texas.

Because the patients at community centers tend to be older, sicker, less affluent and generally more diverse than those treated at big academic medical centers, they are considered more representative of the national population. So, over the years, the community centers have played important roles in developing new treatments for breast, lung and prostate cancer.

And as far as federal administrators know, many of these clinics have sparkling records.

But federal officials have never conducted a systematic review of the community research program. And if Carle’s problems turn out to be any indication, the community centers may not always be adhering to the rigorous protocols of research medicine that the National Cancer Institute expects them to follow. That could call into question the scientific evidence that the community research program amasses.

The investigation is being conducted by the federal Office for Human Research Protections, an arm of the Department of Health and Human Services. So far, the office has issued two letters of criticism — one in June, the second in September — to the nonprofit Carle Foundation Hospital and its affiliated for-profit cancer center.

Meanwhile, the National Cancer Institute has shut down new patient enrollment in the studies at Carle, although it has allowed existing patients to continue experimental treatment there.

Dr. Lori Minasian, director of the National Cancer Institute’s community clinical oncology program, said the agency would apply any lessons from Carle’s human research violations “across the entire network” of community hospitals and doctors. “We’ll look at audits, organizational structure and research oversight,” she said in an interview.

Carle executives declined to comment for this article. But in their official responses to federal authorities — another response is due Tuesday — they say they have made changes, including retraining the principal investigator and other doctors, appointing new oversight managers, and “a top-to-bottom review” of protections for patients in clinical trials.

But they deny trying to cover up problems or that Dr. Stratton was fired for whistle-blowing. She has threatened to sue.

“I was devastated,” Dr. Stratton said recently.

“I have concerns not just about patient safety, but the integrity of the data in the trials,” she said. “My larger concern is that there may be other community hospitals doing research that, like Carle, evolved in a vacuum.”

The National Cancer Institute provides relatively limited financing for the community program. Carle, one of the bigger recipients, received about $1 million last year in federal research support, which does not go far in supporting the many trials under way at any one time. The greater value is the prestige the program bestows on the community clinics, making them regional magnets for doctors and patients alike.

The principal researcher at Carle, Dr. Kendrith M. Rowland Jr., is an oncologist who built a local reputation for offering the latest in cancer care. He once treated the wife of a bank owner who later donated $10 million to the cancer center.

Dr. Rowland, 55, has simultaneously overseen more than 130 clinical trials in more than 20 cancer types, a grant application shows, and he personally enrolled about one-quarter of the 500 patients that Carle signed up for experimental treatment in a typical year.

But Dr. Stratton, whom Carle hired in early 2007 to help oversee the cancer research effort, said Dr. Rowland was headstrong and had resisted her suggestions for improving standards.

Dr. Rowland did not respond to numerous telephone calls and e-mail queries, or to a reporter who visited his office; instead, he sent an aide to say he was too busy to talk. Carle representatives said Dr. Rowland would not comment, nor would the chief executive of the 305-bed hospital, Dr. James C. Leonard, who had fired Dr. Stratton.

Before coming to Carle, Dr. Stratton was well regarded in cancer research circles. She had more than a decade’s experience in clinical trials, including serving as the principal researcher in three national studies of prostate cancer. Dr. Stratton had also led a group that oversaw all drug and device trials for the University of Arizona Medical Center.

And she said that Carle’s institutional review board, which is supposed to monitor patient safety and doctors’ ethics, was too deferential to the researchers and failed to keep its own files.

In the audit that led to her showdown meeting with hospital administrators, there were instances of patients’ having received incorrect doses of drugs, while others were given chemotherapybefore, rather than after, the required lab tests. And one patient was enrolled in a study despite having an implanted brain device that, according to the audit, should have disqualified him for safety reasons.

“I can’t stress enough how serious things are over there as far as noncompliance goes,” she wrote in an e-mail message to the hospital chief last November, shortly before she was dismissed.

In a June 9 letter, the federal investigators said they had found evidence of Dr. Rowland’s “interference” with reporting problems to authorities; “continuing noncompliance” with federal research rules set up to protect patients and data; and “systemic problems involving lapses in continuing review of numerous Carle Clinic cancer studies.” The two reports are posted on a federal Web site.

Carle responded in a July 13 letter to a federal official, obtained by The New York Times. Carle argued that the violations were minor, that it was making improvements and that its doctors performed good research. It also said any interference by Dr. Rowland was not intentional.

Whether lapses at Carle were the result of ambitious doctors taking on more work than their local setup could handle, or shortfalls in financing and oversight, may not be known until the federal investigation concludes.

And Carle may prove an exceptional case. After all, most community programs have provided valuable research without running afoul of federal authorities.

But some experts in community medicine say that many of the local programs simply fly under the federal government’s radar. And they contend that some of those clinics lack the support staff, record-keeping systems and institutional oversight of larger centers to assure proper ethics and patient safety in experimental medicine.

“Trouble occurs when institutions dabble,” LaDale K. George, a Chicago lawyer who has advised dozens of community hospitals performing clinical research, said in an interview. “Well-run, organized, clearly designed, this is an activity that has manageable human risk and minimal compliance risk. Disorganized, decentralized — you have significant risk.”

Turning down trials, cool apps, and swine flu

Alex — Fri, 07 Aug 2009 15:24:50 +0000

Some really fascinating stories get us going into the weekend. Interesting and heartfelt responses to NYT article about cancer trials and why people don’t volunteer for trials… although I’m not convinced of their necessity at all, there’s a very cool story about iphone and Windows apps for clinical trials … and an update on efforts in the U.S. and abroad about progress on trials for a swine flu vaccine…

Why Patients Turn Down Clinical Trials – New York Times – I read with interest your article about the chilling effect that low recruitment for clinical trials has had on the search for meaningful treatments … See all stories on this topic

Clinical trial app choices: Expensive, for charity or in-the-making – mobihealthnews – The market for clinical trials-focused mobile applications just got competitive and complicated. During the past week two new contenders announced … See all stories on this topic

Big drugmakers start trials of swine flu vaccines – Reuters – The launch of clinical trials is a key part of a widening program of work being undertaken by big pharmaceutical companies as they prepare for mass … See all stories on this topic

Swine Flu Spreading; Drug Makers Begin Clinical Trials – DOTmed.com (press release) – Approximately 6000 people of all ages in the US, UK and Germany are being tested and the trial is expected to last for one year. Novartis said the vaccine … See all stories on this topic

New York Times & Parade Champion Clinical Trials

Alex — Mon, 03 Aug 2009 15:03:28 +0000

The New York Times has a story about cancer trials that subtly urges patients to enroll as subjects. There is also a sidebar about how to make the decision to enroll. All in all, a pro-trials approach, which is becoming all too common in most media coverage of trials at the same time that corporate interests assert themselves … Also, a story from a recent Parade magazine urging people to, you guessed, it, enroll in trials. This one is done is such a strenuously blatantly fashion that the subhead is: “Sometimes it take an experiment to make you well.”

Forty Years’ War Lack of Study Participants Said to Hobble Fight … New York Times – Of course, there have been highly successful clinical trials — studies of drugs like Gleevec for chronic myelogenous leukemia and estrogen-blocking therapy … See all stories on this topic

For Patients: Questions to Ask About a Clinical Trial – New York Times – Most who enroll in clinical trials say they want to help themselves and others. But how can patients decide that a trial is worth … See all stories on this topic

Sometimes it Takes an Experiment to Make You Well: Are Clinical Trials Safe – Parade – June B. has a big decision to make. She sits across from me, deep in thought. I’ve just offered her the chance to enroll in a clinical trial of a new treatment. I know the decision will not be easy.

Swine flu vaccine, cancer & “rigged” trials – July 15, 2009

Alex — Wed, 15 Jul 2009 15:34:54 +0000

A vaccine for swine flu is nearing clinical trials testing while at the same time the U.S. is pumping another $1 billion into the vaccine to get it to trials, perhaps this month… A Denver television news station (of all places) has a very interesting story on a report released from watchdog organization Public Citizen saying that a large number of clinical trials results are not accurate because money plays to big an influence in trials… An examination of cancer trials reveals that race plays a part in the rates among African Americans in some significant cancers… all in all, interesting reading for a beautiful Wednesday…

Labs say swine flu vaccine is close to clinical trials – guardian.co.uk – UK – Some are in the experimental stages, while others are approaching the need for clinical trials. However they are “by no means” ready yet, according to the … See all stories on this topic

US to spend another $1 billion on flu vaccine – Reuters – USA – It needs to be safe so testing and clinical trials will start this month. We’ll know a lot more by the end of the summer and it needs to be effective,” she … See all stories on this topic

Are Clinical Trials Compromised By Money? – TheDenverChannel.com -Denver, CO, USA – Are clinical trial rigged? The results skewed? That’s the question asked by Public Citizen in Washington, DC “Many medical journals are becoming marketing … See all stories on this topic

Cancer Does Discriminate – Science Magazine (subscription) – USA – A new study that looks back at dozens of cancer clinical trials concludes that for some cancers, such as lung and leukemia, race makes no difference … See all stories on this topie

Responses to NYT Cancer Research/Money Article

Alex — Tue, 30 Jun 2009 16:28:25 +0000

The letters regarding Gina Kolata’s article in the New York Times Sunday about how grant funding directs a lot of cancer research and engenders an atmosphere of playing it safe in clinical trials are fascinating.

Almost everyone who wrote and is in the “cancer research” field appears to agree with the findings in the article. It begs the question of course: Why are these same people not working to change the atmosphere?

Click here to read the letters.

Cancer research driven by grant system and safe thinking – June 29, 2009

Alex — Mon, 29 Jun 2009 17:32:47 +0000

An excellent article in the New York Times by the always astute and well-informed medical and health writer Gina Kolata sheds light on how cancer research is driven by a grant system that rewards cautious thinking more than promoting bold ideas of how to cure and treat cancer. The article is a nice look at a portion of the “medical industrial complex” that appears to be a self-sustaining enterprise and an embedded part of how health care and research are conducted in the United States.

In a related story also in the New York Times, cancer researchers in Australia have developed a drug that is effective in animal tests at attacking cancer cells. It’s a long way to see if the new approach has validity in human subjects, but it is nice to see progress being made in imaginative ways.