Search This Blog

Tuesday, February 16, 2010

A proposal for a clinical study

Medical science--clinical studies, must be taken with a grain of salt. It is nearly impossible to do science when the thing being studied is as complex and multi-faceted as a human. Such studies attempt to prove that treatment A is better than a placebo (a pretty low standard) or that treatment A is superior to treatment B. The group under study is supposed to be homogeneous--a cohort with the same disease process. I would suggest it is nearly impossible to find a cohort of patients with exactly the same disease. Ultimately, many confounding variables make this sort of science difficult to do and to validate.

All the randomized-placebo-double blind-peer reviewed studies for chronic or post Lyme disease look at lot alike. All patients had prior, treated Lyme disease. All had had received "standard" therapy. And, all had persistent symptoms in the face of prior therapy. "Long term therapy" was defined as limited courses of Rocephin with or without courses of doxycyline. Generally, patient selection required CDC-IgG positivity, 5/10 bands. Of interest, Klempner also studied "sero-negative" patients. This is anomalous since the IDSA has generally claimed that seronegative patients do not suffer with Lyme disease.

Insanity has been defined as: doing the same thing over and over again-- expecting a different result.

I would suggest that another kind of study be designed and carried out. Patients with the same general set of symptoms, for example: migratory joint pains, fatigue and cognitive impairment plus positive Lyme Western Blocks by IgM or IgG standards should be studied. Patients from this cohort should be randomized into two arms: a head-to-head study. Group A would receive IDSA recommended therapy and group B would receive LLMD style therapy. Objective measurements of progress would be agreed upon. These might include: symptom lists, psychometric testing, physical exams and perhaps lab parameters such as a highly sensitive C-reactive protein. Patients would be periodically assessed over a prolonged period of time. For example, patients could be assessed every 3 months for a period of one to two years.

LLMDS in the study could agree upon some general standards, for example, Babesia could be treated with Mepron and Zithromax for 8 weeks. If there were no clinical response, a second course might be Larium plus Artemesin. In general, the physicians would be given flexibility to treat patients differently, based on clinical experience.

This is the sort of study which might provide convincing evidence that treatment for chronic Lyme disease is effective. The disease is different in every patient. It is nuanced. It is complex. Standard study designs which look at only one variable, will never prove the benefits of long term treatment for Lyme disease.

I hear a lot of talk about the need for Lyme studies.

I think, first potential investigators need to develop a study design. The teams needs then to find a partner with credibility and prestige, such as NIH. The cost could be low, particularly if this sort of head to head study could be "piggy-backed" onto another planned or ongoing study. Results, hopefully favorable ones, could be published in a major, peer reviewed journal.


Unknown said...

I appreciate your passion, doc as it is clear that you are working on Lyme not just in the office, but also in your car, while shaving, etc.

One concern I would offer is for the A Group - the ISDA treatment group. How could sick people be asked to receive less than effective treatment? Even if the group is crossed-over, time will have been wasted.

I spent less than 30 minutes online before I received the lab results, so before I even received a diagnosis I knew that if I did need to treat Lyme I would need to find a ILADS/LLMD professional.

Perhaps I would have tried the ISDA route if I had no/poor insurance and/or severe fiscal constraints.

I cannot see another reason, if the number one goal is wellness. And while I would love to contribute to science and the overall good, first and foremost I need to survive and thrive.

Someone has to do something, I agree. I just think it would be hard to fill the A Group.

Lyme report: Montgomery County, MD said...

most patients diagnosed with Lyme disease see IDSA doctors and recieve "standard care" only. Patients recruited for a Lyme study by the NIH would not have your savy about Lyme disease. Other published clinical studies have compared treatment to placebo(sugar pill). At least these patients would recieve some therapy. Unfortuately, this is the only way to obtains "science" which might change the minds of some the the influencial "deciders."

dogdoc said...

Anyone who is a doctor will understand this comment. It is the only way to acheive scientific recognition and thus change in the field of medicine. My field is very similar.

Would the results show us what we wanted to see- ie a clear high percentage of responses with a defined endpoint?

If so, it would not have to be the ivory tower guys doing the study. It would only have to be implemented appropriately so it could not get picked apart post publication. And one would have to be able to get it accepted for publication.

Reguardless of ethics, it would probably have to be a double blinded placebo design. Or it would not acheive the recognition that was desired.

I think it would be difficult to find LLMD's who would be willing to publish the diagnostics and treatments used for all to see. You might be an exception there.

Michele said...

Despite positive Western Blots, PCR & all other tests I was turned down twice by NIH for their study because the exact test they wanted was too long (over a month) ago. We must give up on them or any other govt agency. I saw the saddest show on the internet and I want to tell people because it is all about Lymes. It is called "intervention" and you can see it on So they had a 21 year old that "had developed" rhumetoid arthritis so bad she could not walk and was on serious pain meds her family thinking she was abusing them. Her mom actually did an internet search and begged her to go for a Lymes test. She did and it was positive. She received the standard IDSA treatment but suprise her arthritis came back and worse. So did her need for pain meds. She went to a treatment facility and was again given "two weeks of antibiotics for Lymes" and told sadly that she would always have this horrible arthritis and other pains. She is 21 years old and on disability for her arthritis. I cried.

Michele said...

LYMDmd: Why don't you let a patient (me) who is savy in statistics at the doctorate level do some work using your charts. I would not tamper with the results as I know is often done.
You have the information there so no study has to be done. It already has been done by you seeing your patients. The information just needs to be in a publishable form and I will do that.

Lyme report: Montgomery County, MD said...


Perhaps you can understand my frustrations with "evidence based medicine"--Harvard style.

CD said...

I love the comment 'how could sick people be asked to receive less than effective treatment?' I was in treatment Group A for at least a year, my IDSA primary doc eventually sent me away with a prescription for anti-depressants. He told me, kids in Connecticut had fluid removed from swollen joints after treatment (his form of treatment) and there was no evidence of active Lyme infection. Therefore chronic lyme does not exist.
I've been in Group B since December with excellent results but I had to endure Group A treatment to get here.

worriedmom said...

NatCap sent link for new Nat'l Acad of Sci study project

Project Number: NAS-IOM-BPH-09-06

Wished the study committee would incorporate your experineces and knowledge of the disease.

The project committee did not appear well balance, no names from Lyme community recongized.

Jazzie said...

Don't start it with negative sides, if you are willing to, go for it! remember the song? Don't stop, don't give up, keep trying 2x.

Clinical Trial Recruitment Strategies