Cohorts - Letter to the IACFS/ME

[CBS]

Hi,

I've talked about writing a letter to the IACFS/ME and asking them to consider a leading role in creating cohort definitions to clarify past and future CFS research. I'm looking for input on this. Thanks, Shane

Note: The letter below has been edited to include suggestions received after being originally posted.

January 5, 2010



c/o: Fred Friedberg, Ph.D., President, Board of Directors
The International Association for CFS/ME
27 N. Wacker Drive Suite 416
Chicago, IL 60606


Dear IACFS/ME Board of Directors,

I am writing as a patient that was diagnosed with CFS in 1994. I am also writing as a former employee of the Stanford Center for Disease Prevention and a Stanford University Research Affiliate.

The recent study linking CFS to the XMRV retrovirus; "Detection of an Infectious Retrovirus, XMRV, in Blood Cells of Patients with Chronic Fatigue Syndrome" V.C. Lombardi, et al., Science, 8 Oct. 2009, was a watershed moment. Sound research with carefully described cohorts will be needed to verify or disprove the association of this retrovirus with CFS (as well as any other agent associated with CFS).

As the leading research body and given the IACFS/ME leading response to the inadequacies of the Center for Disease Control’s recently proposed 5-year plan, you are in a unique position. As your mission statement emphasizes, “The mission of the IACFS/ME is to promote, stimulate and coordinate the exchange of ideas related to CFS, ME and fibromyalgia (FM) research, patient care and treatment.”

CFS has a long and frustrating history of research clouded by extremely poor cohort definition, especially studies using the most recent CDC definition which may result in cohorts with up to 75% of identified “CFS” patients actually meeting the diagnostic criteria for primary depression.

As I am not a CFS researcher, I will not presume to have had as an exposure to research on this disorder as the IACFS/ME board. However, I do have experience with methodology and it is appears that a relatively clear and concise taxonomy, by which the value and or applicability of study results to any specific population may be judged, does not exist.

By way of example only, may I suggest that all CFS research might be classified by cohorts and their essential elements such as:

• CFS preceded by documented infectious episode (e.g. one criteria may be that a cohort meets the Canadian Consensus definition of CFS),
• CFS preceded by suspected infectious episode
• CFS with sudden onset, non-infectious episode
• CFS with gradual onset
• Chronic fatigue of undetermined etiology (not consistent with depression or anxiety)
• Chronic fatigue (consistent with depression or anxiety, e.g. cohort meets CDC/Reeves 'empirical definition' - 2005)

While there are sure to be many questions about appropriate methodology for the detection of the XMRV retrovirus and what, if any role such a virus plays in CFS/ME, the question of CFS patient identification and classification is an issue that the IACFS/ME can address impartially with unparalleled credentials.

The addition of such a taxonomy would be a significant contribution towards the proper interpretation of past research as well as a valuable tool for future CFS investigation.

The association of CFS with XMRV highlights the need for such a classification system but the need for such a system is not limited to XMRV research. Such a classification system would be of great benefit for interpreting all CFS research as well as provide a framework that is now lacking for young scientists entering the field of CFS investigation.

If you have already undertaken the creation of such a classification system, I thank you. If this has not been undertaken, I would urge you to consider doing so and doing it sooner rather than later. In two months any such action may be dismissed as reactionary and potentially biased or political.



Respectfully,



XXXXXXXXXXX

 

[gracenote]

A couple of questions:

Shane,

I think this is excellent and I'm so glad you're doing it.

As I am not a CFS researcher, I will not presume to have had as wide an exposure to this disorder as the IACFS/ME board.

Might you want to say, "I will not presume to have had as wide an exposure to research on this disorder as the IACFS/ME board"? I'm thinking all of us have had very wide exposure to this disorder.

Might there also be this category?

CFS with sudden onset, non-infectious episode

Just some thoughts. Let me say again, I think this is excellent.

 

[CBS]

Shane,

I think this is excellent and I'm so glad you're doing it.


Might you want to say, "I will not presume to have had as wide an exposure to research on this disorder as the IACFS/ME board"? I'm thinking all of us have had very wide exposure to this disorder.

Might there also be this category?

• CFS with sudden onset, non-infectious episode

Just some thoughts. Let me say again, I think this is excellent.

Gracenote,

As always, thank you for your thoughtful input (be it on this letter or gently reminding me that tone matters).

I have incorported your suggestions.

Shane

 

[fresh_eyes]

I'm so glad you're doing this, Shane. One thing: wasn't the original Science paper published Oct. 8?

 

[leelaplay]

I'm glad you're doing this too Shane. Thank you.

Do you think it would be good to also include that the ME/CFS definitions used should be specified, with the Canadian Consensus being the preferred, the Fukuda (which year is the good one?) second, and that the Reeves is not acceptable as it includes people with depression who don't have ME/CFS and would skewer the results?

I'm very interested in their response. IMHO the IACFS/ME and the CAA should both be sending letters to all researchers explaining the importance of this and should have statements on their web pages as to what their position is and what actions they've taken to ensure all newcomers to the field are aware of the need for this.

If not, maybe there's something we could do.

 

[Kati]

Hi Shane, great job and thank you for your contribution.

I agree with IslandFinn to mention the canadian consensus as a diagnosis tool, since a non-educated physician can diagnose with the CDC criteria. But all in all this is a great, respectful letter that I am sure will be appreciated by IACFS

Kati

 

[CBS]

Fresh Eyes,

You're right. The Science Express article was published 10/8, the Scuence article was actually published 10/23. The WPI pres release was 10/9.

 

[CBS]

I'm glad you're doing this too Shane. Thank you.

Do you think it would be good to also include that the ME/CFS definitions used should be specified, with the Canadian Consensus being the preferred, the Fukuda (which year is the good one?) second, and that the Reeves is not acceptable as it includes people with depression who don't have ME/CFS and would skewer the results?

I'm very interested in their response. IMHO the IACFS/ME and the CAA should both be sending letters to all researchers explaining the importance of this and should have statements on their web pages as to what their position is and what actions they've taken to ensure all newcomers to the field are aware of the need for this.

If not, maybe there's something we could do.

Island Finn and Kati,

Good suggestions. I did not want to appear as though I was saying that I wouldn't presume to have the amount of research experience as they do and then fill in all of the details I thought ought to be there. That said, if you wnat some thing a certain way, its always best to just say so and then let then come up with good reasons for why it should be different. I opted for a middle ground by suggesting the Canadian consensus definition at one end and the Reeves empirical definition at the other end. I wouldn't want to say that research using the Reeves definition shouldn't be categorized. I'd rather it be clearly categorized as something other than CFS research and treated accordingly.

As for the CAA, I'm thinking of sending a copy to the CAA as well and asking that if the IACFS/ME would take the lead in creating this that the CAA consider working together to get the word out to physicians and researchers. I'll be back here asking for help if this gets to that point.

Any other thoughts? I'm hoping to get this out at the end of today or early tomorrow.

Thanks for all the good feedback, Shane

 

[leelaplay]

Island Finn and Kati,

Good suggestions. I did not want to appear as though I was saying that I wouldn't presume to have the amount of research experience as they do and then fill in all of the details I thought ought to be there. That said, if you wnat some thing a certain way, its always best to just say so and then let then come up with good reasons for why it should be different. I opted for a middle ground by suggesting the Canadian consensus definition at one end and the Reeves empirical definition at the other end. I wouldn't want to say that research using the Reeves definition shouldn't be categorized. I'd rather it be clearly categorized as something other than CFS research and treated accordingly.

As for the CAA, I'm thinking of sending a copy to the CAA as well and asking that if the IACFS/ME would take the lead in creating this that the CAA consider working together to get the word out to physicians and researchers. I'll be back here asking for help if this gets to that point.

Any other thoughts? I'm hoping to get this out at the end of today or early tomorrow.

Thanks for all the good feedback, Shane

I think you're doing a marvelus job Shane. You make it clear that you are not writing as a lay-person.

I agree that the Reeves (and Oxford) definitions should be very specifically included so that the results can be compared. But it wasn't clear to me that that's what you were saying. Maybe that's just my fog-impaired vision. Oh - I just reread your post, did you edit it to include the definitions?

I think the Canadian or Fukuda could be used for the first four catgories.

You're better on the science than I am. I thought it would be interesting to chunk them according to definitions first, with onsets a secondary category so that it is clear that the definitions skewers the results, and to see if the onset affects results:

1. Canadian Consensus Documents definition of ME/CFS or Fukuda (is '98 the good version?) - consistent with an organic disease
a) preceded by documented infectious episode
b) preceded by suspected infectious episode
c) with sudden onset, non-infectious episode
d) with gradual onset

2.'Chronic fatigue' of undetermined etiology (not consistent with depression or anxiety)

3. CDC/Reeves 'empirical definition' - 2005 (consistent with depression or anxiety )

Just my opinion.


And absolutely agree re involving the CAA.

Again, thanks for doing this Shane!

if

 

[CBS]

Better or too long - lacking focus?

January 5, 2010



c/o: Fred Friedberg, Ph.D., President, Board of Directors
The International Association for CFS/ME
27 N. Wacker Drive Suite 416
Chicago, IL 60606


Dear IACFS/ME Board of Directors,

I am writing as a patient that was diagnosed with CFS in 1994. I am also writing as a former employee of the Stanford Center for Disease Prevention and a Stanford University Research Affiliate.

The recent study linking CFS to the XMRV retrovirus; "Detection of an Infectious Retrovirus, XMRV, in Blood Cells of Patients with Chronic Fatigue Syndrome" V.C. Lombardi, et al., Science, 8 Oct. 2009, was a watershed moment. Sound research with carefully described cohorts will be needed to verify or disprove the association of this retrovirus with CFS (as well as any other agent associated with CFS).

As the leading research body and given the IACFS/ME leading response to the inadequacies of the Center for Disease Control’s recently proposed 5-year plan, you are in a unique position. As your mission statement emphasizes, “The mission of the IACFS/ME is to promote, stimulate and coordinate the exchange of ideas related to CFS, ME and fibromyalgia (FM) research, patient care and treatment.”

CFS has a long and frustrating history of research clouded by extremely poor cohort definition, especially studies using the most recent CDC definition which may result in cohorts with up to 75% of identified “CFS” patients actually meeting the diagnostic criteria for primary depression.

As I am not a CFS researcher, I will not presume to have had as an exposure to research on this disorder as the IACFS/ME board. However, I do have experience with methodology and it is appears that a relatively clear and concise taxonomy, by which the value and or applicability of study results to any specific population may be judged, does not exist.

By way of example only, may I suggest that all CFS research might be classified by cohorts and their essential elements such as:

• CFS preceded by documented infectious episode (e.g. one criteria may be that a cohort meets the Canadian Consensus definition of CFS),
• CFS preceded by suspected infectious episode
• CFS with sudden onset, non-infectious episode
• CFS with gradual onset
• Chronic fatigue of undetermined etiology (not consistent with depression or anxiety)
• Chronic fatigue (consistent with depression or anxiety, e.g. cohort meets CDC/Reeves 'empirical definition' - 2005)

Other potential categorization scenarios might include established diagnostic criteria with clear guidance as to which cohort each case definition would apply (possibly collapsing across categories where meaningful distinctions are difficult to discern).

• Canadian Consensus Documents definition of ME/CFS or Fukuda - consistent with an organic disease:

a) preceded by documented infectious episode
b) preceded by suspected infectious episode
c) with sudden onset, non-infectious episode
d) with gradual onset
​

A third possible distinction across cohorts may be to classify research based upon the length of time the cohort has been suffering from CFS. Many researchers, including Drs. Klimas and Bateman, have publicly expressed their belief that there is a natural course for severe CFS and that a significant majority of patients eventually experience very similar issues such as neural and cardiovascular dysfunction.

While there are sure to be many questions about appropriate methodology for the detection of the XMRV retrovirus and what, if any role such a virus plays in CFS/ME, the question of CFS patient identification and classification is an issue that the IACFS/ME can address impartially with unparalleled credentials.

The addition of such a taxonomy would be a significant contribution towards the proper interpretation of past research as well as a valuable tool for future CFS investigation.

The association of CFS with XMRV highlights the need for such a classification system but the need for such a system is not limited to XMRV research. Such a classification system would be of great benefit for interpreting all CFS research as well as provide a framework that is now lacking for young scientists entering the field of CFS investigation.

If you have already undertaken the creation of such a classification system, I thank you. If this has not been undertaken, I would urge you to consider doing so and doing it sooner rather than later. In two months any such action may be dismissed as reactionary and potentially biased or political.



Respectfully,



XXXXXXXXXXX

 

[gracenote]

I'm lacking focus

ComeBackShane,

I am very much lacking focus tonight so my comments will be about length rather than content.

I copied and pasted this to a blank word document, and using 9 point verdana, single spaced, it comes out to a page and a half. My thought is that one single page would be great. And as you are sending this to an already knowledgeable doctor, I think you can make your point with less words rather than more. Now HOW to shorten this is the hard part and I can't right now help you with it. I liked your first attempt because it seemed to get right to the point and visually I could see the end.

These are just MY unfocused thoughts after this day of following the results of Simon Wessely's disingenuous cohort choice.

But please, don't not do this because you may not feel it is exactly right. (Like this sentence I just wrote I think you know what I mean, but I can't figure out how to get out the repeat negatives!) What you started with was great. What you have now is probably great content-wise, also. So either one I think is just fine.

Gotta go check out what's happening on The Fight is On! thread.

Gracenote

 

[jewel]

Hi ComeBackShane: I am just a relative newbie here, and just lost the post I was trying to write. Am I in any position, then, to provide even the most basic of advice? Probably not. I really wanted first to echo/paraphrase Gracenote's comment regarding sending this off, even if it is not exactly how you want it (i.e., not letting the "perfect" be the enemy of the "good" (or even "great")). Also, I agree that the shorter version is preferable. I very much like that you establish your credentials early on, both your background in research and experience as a PWC. Thank you for taking this on. Finally, the one last little bitty thing is that in scanning your last version, I did note one little typo/omission I think As I am not a CFS researcher, I will not presume to have had as an exposure to research on this disorder as the IACFS/ME board. Somewhere in there it should say "as much of" prior to "an exposure." I think... Anyway, I find myself losing little bits of statements sometimes when I cut and paste. Of course, it is obvious that you would re-proof read it, but sometimes if I've drafted and redrafted something, I will actually miss this type of thing. Any way, thanks! Jule

 

[CBS]

Final Version - IACFS/ME Cohort Letter

First, thanks to everyone who commented both on this thread and via PM. I sent e-mail this morning to the Dr. Freidberg of the IACSF/ME and Dr. Vernon, Scientific Director of the CFIDS AA (IACFS/ME board). I will be sending copies of the same letter via USPS.

Here is the final letter along with the accompanying 'cover letters.' I'll keep you posted on any responses.

-------- Original Message --------
Subject: IACFS/ME - Patient cohort categorization and study design standards
Date: Wed, 06 Jan 2010 10:50:45 -0700

Dear Dr. Friedberg,

I am writing to you in your capacity as President of the IACFS/ME. I have attached a letter in pdf form which I do hope you will take the time read. I am a patient with CFS as well as a former research associate in the medical sciences at Stanford University.

As the entire CFS community is aware, many opportunities and avenues for investigation are presenting themselves at this time. It is my hope that the IACFS/ME will take a leading role in helping to guide and appropriately interpret both past and future research into CFS.

My thanks and appreciation for your time.

Sincerely,


XXXXXXXXXXXXXX

-------- Original Message --------
Subject: Attn: Dr. Susan Vernon - IACFS/ME - Patient cohort categorization and study design standards
Date: Wed, 06 Jan 2010 11:05:36 -0700

Dear Dr. Vernon,

I would first like to express my appreciation for your prompt response to the XMRV/CFS study released by Dr Erlwein et al.on January 5th, 2005. Having the tools in place and the expertise to evaluate all research into CFS has never been more important than now.

Aside from saying thank you, my primary purpose for writing was to draw your attention to a letter that I recently sent to the IACFS/ME, asking that the board consider taking a lead role in creating a clear and concise mechanism for categorizing both past and future research into CFS by cohort. If the IACFS/ME undertakes such a task and this is something that you agree would be an important step towards clarifying what at times has been a very cluttered history and providing clear guidance for future investigations, then I am asking that the CFIDS Association of America consider publicly endorsing (and perhaps participating in) the IACFS/ME efforts to this end.

Again, my heart felt thanks for your recent response to the Imperial College of London study. Perspective has never been more important than now for everyone.

Sincerely,

XXXXXXXXXXXXX

The actual letter:

January 6, 2010



c/o: Fred Friedberg, Ph.D., President, Board of Directors
The International Association for CFS/ME
27 N. Wacker Drive Suite 416
Chicago, IL 60606


Dear IACFS/ME Board of Directors,

I am writing as a patient that was diagnosed with CFS in 1994. I am also writing as a former employee of the Stanford Center for Research in Disease Prevention and a Stanford University Research Affiliate.

The recent study linking CFS to the XMRV retrovirus; "Detection of an Infectious Retrovirus, XMRV, in Blood Cells of Patients with Chronic Fatigue Syndrome" V.C. Lombardi, et al., Science, 8 Oct. 2009, was a watershed moment. Sound research with carefully described cohorts will be needed to verify or disprove the association of this retrovirus with CFS (as well as any other agent suspected to be associated with CFS).

As the leading research body in CFS, and given the IACFS/MEs strong, yet constructive response to the inadequacies of the Center for Disease Controls recently proposed CFS Public Health Research Program 5-year Strategic Plan, you are in a unique position. As your mission statement emphasizes, The mission of the IACFS/ME is to promote, stimulate and coordinate the exchange of ideas related to CFS, ME and fibromyalgia (FM) research, patient care and treatment.

CFS has a long and frustrating history of research clouded by extremely poor cohort definition, especially studies using the most recent CDC definition which may result in cohorts with up to 75% of identified CFS patients actually meeting the diagnostic criteria for primary depression.

As I am not a CFS researcher, I will not presume to have had as much exposure to research on this disorder as the IACFS/ME board. However, I do have experience with methodology and it is appears that a relatively clear and concise taxonomy - by which the value and/or applicability of study results to any specific population may be judged - does not exist.

By way of example only, may I suggest that all CFS research might be classified by cohorts and their essential elements? The rough outline of one possible scenario may be the following:

• CFS preceded by documented infectious episode (e.g. one criteria may be that a cohort meets the Canadian Consensus definition of CFS),
• CFS preceded by suspected infectious episode
• CFS with sudden onset, non-infectious episode
• CFS with gradual onset
• Chronic fatigue of undetermined etiology (not consistent with depression or anxiety)
• Chronic fatigue (consistent with depression or anxiety, e.g. cohort meets CDC/Reeves 'empirical definition' - 2005)

While there are sure to be many questions about appropriate methodology for the detection of the XMRV retrovirus and what, if any role such a virus plays in CFS/ME, the question of CFS patient identification and classification is an issue that the IACFS/ME can address quickly, impartially and with unparalleled credentials.

The addition of such a taxonomy would be a significant contribution towards the proper interpretation of past research as well as a valuable tool for future CFS investigation. To that same end, I would also strongly suggest that the IACFS/ME consider the creation of guidelines for researchers emphasizing the need for careful design, especially with regards to the statistical power of studies. Research in to CFS, a multifaceted disorder that may be the culmination of a number of concurrent agents/events, would benefit a great deal if studies were designed with the potential to detect relatively small but statistically stable, and potentially clinically significant contributing factors. I do appreciate that such guidelines will raise financial concerns as they would call for larger homogenous cohorts meeting specific diagnostic criteria. That said, a small study of heterogeneous patients with statistical power that is not sufficient to detect a factor that makes a stable contribution to part of the CFS picture, is more likely to discourage further potentially fruitful research than move us closer to a better understanding of this disease.

The association of CFS with XMRV highlights the need for a classification system and specific research guidance/standards but the need for such a system is not limited to XMRV research. Such a classification system would be of great benefit when interpreting all CFS research. It would also provide a framework that is now lacking for young scientists entering the field of CFS investigation.

If you have already undertaken the creation of such a classification system and the creation of guidelines, I thank you. If this has not been undertaken, I would urge you to consider doing so and doing it sooner rather than later. In two months any such action may be dismissed as reactionary and potentially biased or political in nature.



Respectfully,




XXXXXXXXXXXXXX





cc:
The CFIDS Association of America c/o Dr. Suzanne D. Vernon, Scientific Director

 

[CBS]

Dr. Friedberg's response (and it's not even noon yet!)

-------- Original Message --------
Subject: Re: IACFS/ME - Patient cohort categorization and study design standards
Date: Wed, 6 Jan 2010 13:33:06 -0500


Thanks, Shane. I've circulated your letter and attachment to the board for their feedback. will get back to you.

fred

I am looking forward to the IACFS/ME board's response and I am very pleased with Dr. Friedberg's quick response.

 

[gracenote]

I am looking forward to the IACFS/ME board's response and I am very pleased with Dr. Friedberg's quick response.

Way to go Shane. Thanks for letting us in on your process and the quick response. I'm looking forward to hearing more as it comes in. You have set a good example for all of us. Thank you.

 

[Navid]

.....

shane:

great job!!!! you write really well...thanks for taking this on.

warmly, lisa

 

[CJB]

I am looking forward to the IACFS/ME board's response and I am very pleased with Dr. Friedberg's quick response.

Awesome. :Sign Good Job:

 

[MEKoan]

I just wanted to spread some rose petals at your feet, Shane.

 

[leelaplay]

YAY Shane!:Sign Good Job:

 

[alice1]

Thankyou Mr Shane!!!!!