emo new Cochrane review - Hepatitis C: the key questions answered

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5 years 2 weeks ago #24739

Today's Guardian has the following headline over an article written by Sarah Boseley Health editor:
'Miracle' hepatitis C drugs costing £30k per patient 'may have no clinical effect'
Review concludes drugs hailed as cure for potentially fatal liver disease may clear virus from blood, but there is no evidence they prevent harm or save lives.

The new review is I understand titled Hepatitis C: the key questions answered
Please one of you who can, hyperlink the article here


G2, infected maybe in 1971?
Diagnosed HVnon-A non-B 1980s, revised to HVC 1990's.
Treatment naive. Fibroscan & bloods all normal ranges.
Viral load 7million,
began Redemption trial4, 12-week generic Sof/Vel (Incepta) 2017. Week 4 UND, Week 12UND, SVR24
Thank-yous to my doctor for the script, to Jan at FixHepC for wrangling, and to Dr Freeman for courage.
Kia kaha e hoa ma!

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5 years 2 weeks ago #24742

Hi Mnem,

This seems like a very strange review from the Cochrane group, which is usually well respected for medical myth-busting.

For anyone interested, here is a link to the Guardian article:

www.theguardian.com/society/2017/jun/08/...e-no-clinical-effect

Here is a link to the abstract of the paper:

onlinelibrary.wiley.com/doi/10.1002/14651858.CD012143.pub2/full

As far as I can understand, the conclusion of this paper is that patients with hepatitis C will not die straight away if they take a placebo or a modern DAA and get a Sustained Virological Response, and therefore, there is no proof that DAAs will prevent people who are sick from dying. Duh....

Well, since we all know that hepatitis C is a slow killer, this is probably not completely false. But if you ask a dumb question, you will get a dumb answer... And then somebody else will mis-quote it to arrive at an even dumber headline.

Speaking as someone who is cured of hep-C (and who now feels a heck of a lot better than when I had it) I would recommend to file and forget all this under the "dumb science" folder. Or maybe nominate it for a prize here?

www.improbable.com/ig/winners/

Please check out that last one (Perception Prize) about investigating if things look different when bending over and looking through your legs :)


Cheers,

Edit:

OK, I just went and stood on my head for two minutes. The conclusion of the paper should really be "compared to taking a placebo, there is no measurable life-threatening risk in taking DAAs"...

So just do it, and get yourself cured!


Diagnosed Jan 2015: GT3, A0+F0/F1. Fatigue + Brain-Fog.
Started Sof+Dac from fixHepC 10-Nov-2015. NO sides.
Pre-Tx: AST 82, ALT 133, Viral Load 1 900 000.
Week4: AST 47, ALT 58. VL < 15 (unquantifiable).
Week12 (EOT): AST 30, ALT 26, VL UND
Week16 (EOT+4): AST 32, ALT 28, GGT 24, VL UND
Week28 (EOT+16): AST 26, ALT 22, GGT 24, VL UND
Ever grateful to Dr James.

Relapsed somewhere after all that... Bummer!

Jan 2018: VL 63 000 (still GT3).
Last Edit: 5 years 2 weeks ago by Vororo.
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5 years 2 weeks ago #24746

:lol: Hi Vororo,

Looking at the report in a bit more detail, it has the following statement:

"Objectives: To assess the benefits and harms of DAAs in people with chronic HCV."

They then go on to state that they investigated all the clinical trials of DAAs they could discover irrespective of type including "unpublished" and "grey" trials. It appears they also included unsuccessful trials in their investigation of the 51 DAAs they state are involved. So even something that was determined in trial to be unsafe or ineffective against HCV is included in the data?

Reading through the abstract it appears that the investigations actually looked at whether the trials conformed to ideal best practices including allocation of participants by such means as random computer assignment using a "locked" computer and other similar type criteria. i.e. It was a retrospective study (audit) of the methodology of the clinical trials using strict criteria as to what complied with their definition of best practice. This is good! I've conducted many similar "Quality Audits" in my industry, they are an excellent means of keeping the participants honest and driving continuous improvement in standards. We can always do better and this review seems to have highlighted quite a few areas where clinical trials can be improved based on their findings of "the quality of evidence is very low" for compliance with their criteria.

However.....we need to remember that the clinical trials under review were to determine the efficacy and safety of the DAA involved against HCV as measured by plasma RNA levels and adverse events at predetermined points during and post treatment. They were not and were never intended to be whole of life studies of the participants health. Out of the 51 DAAs trialled, something like 25-33% have been approved for use with the rest presumably being determined insufficiently effective or safe although it seems the results from these are included in the data used in conclusions of the authors.

Now go back and read the quoted Objective at the start of my post. As far as I can determine these researchers have audited a large number of clinical trials for compliance with what they consider best practice in a clinical trial and found many areas for procedural improvement due to what they claim is "very low quality evidence". But they have then used that same allegedly poor evidence (including that from all the unsuccessful trials) to extrapolate about the long term prognosis for those taking approved DAAs.

From my perspective, their study approach of investigating procedural elements/reporting of clinical trials does not constitute a meaningful analysis of their stated objective of "assessing the the benefits and harm of DAAs" and thus their conclusions regarding that aspect look to be flawed.


G3a since '78 - Dx '12 - F4 (2xHCC)
24wk Tx - PEG/Riba/Dac 2013 relapsed
24wk Tx - Generic Sof/Dac/Riba 2015/16 relapsed
16wk Tx - 12/01/17 -> 03/05/17 NS3/NS5a + Generic Sof
SVR7 - 22/06/17 UND
SRV12 - 27/07/17 UND
SVR24 - 26/10/17 UND
:cheer: :cheer: :cheer:
Last Edit: 5 years 2 weeks ago by Gaj. Reason: Can't spell
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5 years 2 weeks ago #24747

Couple of quotes from deep in the paper, including an admission that the data they studied is insufficient to determine long term effects of treatment.

"We chose pragmatically to only assess outcomes at one assessment time point, that is, the trial's result as provided at maximum follow-up. Most trial results were only short-term results. Hence, our results can neither confirm nor reject that DAAs have clinical long-term effects, which is a further limitation of our present review results, especially because most of the harmful effects of hepatitis C take years to develop."

"The combined intervention period and follow-up period ranged from one day to 120 weeks with an average of 34 weeks."


G3a since '78 - Dx '12 - F4 (2xHCC)
24wk Tx - PEG/Riba/Dac 2013 relapsed
24wk Tx - Generic Sof/Dac/Riba 2015/16 relapsed
16wk Tx - 12/01/17 -> 03/05/17 NS3/NS5a + Generic Sof
SVR7 - 22/06/17 UND
SRV12 - 27/07/17 UND
SVR24 - 26/10/17 UND
:cheer: :cheer: :cheer:
Last Edit: 5 years 2 weeks ago by Gaj.
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5 years 2 weeks ago #24749

Please see my blog post about it here: fixhepc.com/blog/item/81-bad-science.html

Yesterday the Guardian published and article called 'Miracle' hepatitis C drugs costing £30k per patient 'may have no clinical effect'

www.theguardian.com/society/2017/jun/08/...e-no-clinical-effect

The problem with this sensationalist headline is that while it is reporting what was said by the Cochrane Collaboration what they looked at was trial specifically designed to test SVR rates, and not specifically designed to look at long-term outcomes.

Here is a commentary from Dr Andrew Hill and the study to which he refers which was presented at AASLD in 2015 and published in Clinical Infectious Diseases.

Total rubbish! Here is our paper showing a really strong correlation between curing HCV and improved survival.

They only had 16 deaths included in the analysis!

Please see the attached paper where we had much longer follow up and showed a strong effect of SVR on improved survival. Our analysis included 2210 deaths - slightly more than the Cochrane study!


Here is Dr Hill's AASLD presentation:


File Attachment:

File Name: AASLD_Outc...IDES.pdf
File Size:113 KB


And here is the full journal article from Clinical Infectious Diseases:

File Attachment:

File Name: HepatitisC...ival.pdf
File Size:366 KB

Attachments:

YMMV
Last Edit: 5 years 2 weeks ago by DrJames.
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5 years 2 weeks ago #24772

"Review concludes drugs hailed as cure for potentially fatal liver disease may clear virus from blood, but there is no evidence they prevent harm or save lives."

I find out whether I am 12 weeks SVR post treatment this Tuesday. I don't ask for much, and trying to keep things simple, I will be very happy to fall into the category underlined in the quote.

As to the second bit about evidence of DAA's saving lives, I am not that well read on the subject, but I suspect there is not a lot of evidence that they don't either.

And an after thought, what are DAA's supposed to do other then clear the virus, guarantee a lottery win as well??

Yours all with fingers crossed,

Jeff


GT3a 1990 Failed Inter 1998, comb in 2000. HCC 2012
Started 24/52 Sof/Dac 27th October 2015.
1. Bloods 2 October 2015: AST - 165 (20-40), ALT - 265 (5-40), GGT 189 (5-50)
2, Bloods 20 November 2015: ALT etc normal; VL 19
3. Bloods 8 January 2016: AST - 40, ALT - 59, GGT 48 VL RNA UND
4. EOT 12 April 2016 - blood tests: all is well, CT scan: okay
5. AFP 11 June 2016: 4 ref< 11
6. VL July 2016: DET
7. Oct16 start treat - June17 UND
8. Jun 18, lfts okay, platelets a bit low.
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5 years 2 weeks ago #24773

And an after thought, what are DAA's supposed to do other then clear the virus, guarantee a lottery win as well??

Yes, a proper title for this study would have been DAA therapy is no more dangerous than placebo.


YMMV
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5 years 2 weeks ago #24790

Re: "Yesterday the Guardian published and article called 'Miracle' hepatitis C drugs costing £30k per patient 'may have no clinical effect"

I didn't want to harp on too much about this article, but I decided to investigate the Lady Lottery luck theme instead and bought five $2 scratch lottery tickets after seeing the liver clinic today. From today's efforts I have to report:

a) DAA's do not appear to positively influence the outcome of lotteries.

The null hypotheses was that DAA's had a negative affect - but then again, my luck with lotteries is pretty f..ked anyway.

I can also advise that while talking about my blood results with the specialist, it appears my old mate (Mr f....king HCV) has deserted me (is that what UND means?) after some 27 years. "no clinical effect" ??? Please explain??

Yours


Jeff


GT3a 1990 Failed Inter 1998, comb in 2000. HCC 2012
Started 24/52 Sof/Dac 27th October 2015.
1. Bloods 2 October 2015: AST - 165 (20-40), ALT - 265 (5-40), GGT 189 (5-50)
2, Bloods 20 November 2015: ALT etc normal; VL 19
3. Bloods 8 January 2016: AST - 40, ALT - 59, GGT 48 VL RNA UND
4. EOT 12 April 2016 - blood tests: all is well, CT scan: okay
5. AFP 11 June 2016: 4 ref< 11
6. VL July 2016: DET
7. Oct16 start treat - June17 UND
8. Jun 18, lfts okay, platelets a bit low.
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5 years 2 weeks ago #24791

Congratulations Sabrecat!

I think it is technical speak for "you win".

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  • Mnem
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5 years 2 weeks ago #24792

Hi Jeff, You are the latest lucky winner of fixhepc! It is in no way a lottery, we all seem to get cured, even though it takes some longer than others.
That Cochrane paper, if nothing else, has given us a laugh. In this situation we hepc-ers get the last laugh


G2, infected maybe in 1971?
Diagnosed HVnon-A non-B 1980s, revised to HVC 1990's.
Treatment naive. Fibroscan & bloods all normal ranges.
Viral load 7million,
began Redemption trial4, 12-week generic Sof/Vel (Incepta) 2017. Week 4 UND, Week 12UND, SVR24
Thank-yous to my doctor for the script, to Jan at FixHepC for wrangling, and to Dr Freeman for courage.
Kia kaha e hoa ma!
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5 years 2 weeks ago #24795

Yay :woohoo: :woohoo:
That's fantastic Sabrecat (the UND that is...not your lack of luck with Lady Lottery)! Some mates you don't need anymore.


G1a probably early 1980's, Biopsy F1(2010), F2-F3(2015). VL 5+mill; 2+mill (2014) Tx naive. Accessed Sof/Led through Dr Freeman at GP2U and Buyers Club (lifesavers!!!)
Commenced tx 12/11/15. 9 wk: VL <15 Detected but LFT = Normal 12 week results: UND (Yay!) Due to slow response commenced Sof/Dac 4 Feb for 12 weeks. EOT @ 24 weeks 27 April 2016. (With thanks to Dr Freeman et al). SVR11 result: VL 1,950,000. It's back!
New tx 030916 (Viekira Pak, Solvadi, Ribavirin UND @ 111116. EOT 170217.
SVR12 and SVR 24...
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5 years 2 weeks ago #24797

Jeff! Jeff! you are there! It is over. Sooo pleased for you! #magic


Genotype 3 30 years, 2x treatment interferon/ribavirin non responder. Cirrhosis 17 years. Fibroscan, decompensating, 40 down to 22 by 29/3/16- now down to 6.5, normal, no cirrhosis. Started Buyers Club Sof/Dac 14 Nov 15. SVR 12 29/0716
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5 years 2 weeks ago #24798

Hazel wrote:

Jeff! Jeff! you are there! It is over. Sooo pleased for you! #magic

Hi Hazel, I noticed from your signature:

"Fibroscan 40 down to 22 by 29/3/16- 10/16 dropped to 9.5, no cirrhosis. Started Buyers Club Sof/Dac 14 Nov 15. SVR 12 29/0716"

that getting rid of our unwanted friend may be the beginning of more good news liver health wise. I always wondered if what they say about the liver repairing itself is entirely true .......

A big reason for me undertaking therapy was to reduce the morbidity associated with the liver being beaten around by the bug.

I thought was was SVR at 12 weeks just before the blood test. After the Ribavirin wore off I was energy +.

If this gets even more better, then I may well assume he old boot is repairing itself. I can only assume as my liver was chopped up a bit so fibroscans do not really work with me (at least this is what I was told at one liver clinic).


Yours


Jeff

P.S. all the best on your own stunning result.


GT3a 1990 Failed Inter 1998, comb in 2000. HCC 2012
Started 24/52 Sof/Dac 27th October 2015.
1. Bloods 2 October 2015: AST - 165 (20-40), ALT - 265 (5-40), GGT 189 (5-50)
2, Bloods 20 November 2015: ALT etc normal; VL 19
3. Bloods 8 January 2016: AST - 40, ALT - 59, GGT 48 VL RNA UND
4. EOT 12 April 2016 - blood tests: all is well, CT scan: okay
5. AFP 11 June 2016: 4 ref< 11
6. VL July 2016: DET
7. Oct16 start treat - June17 UND
8. Jun 18, lfts okay, platelets a bit low.
Last Edit: 5 years 2 weeks ago by sabrecat.
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5 years 2 weeks ago #24801

Thanks Jeff,
I should change that- wasn't actually fibroscan, was ultra ultrasound, is the kPa I mean of course. And a further drop, now 8.5 so I am F2 after so many years of F4..... I didn't know, when I started, that it was possible. I didn't know what feeling well was like either, so long under a different, cloudy sky I had lost track of what blue looked like. I can see clearly now, as the song goes. May your clouds keep rolling back! Your signature is due for that exciting update. :)


Genotype 3 30 years, 2x treatment interferon/ribavirin non responder. Cirrhosis 17 years. Fibroscan, decompensating, 40 down to 22 by 29/3/16- now down to 6.5, normal, no cirrhosis. Started Buyers Club Sof/Dac 14 Nov 15. SVR 12 29/0716
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5 years 2 weeks ago #24802

Ha ha, it was a good run while it lasted! But if Bristol Myers Squibb and Gilead are denouncing their conclusions, their "stature" may now be permanently diminished. Talk about shooting yourself in the foot :cheer: :-1: I'm cured and I know it for damn sure, I feel terrific!


Gt 1a, F0, VL 6.5 million, AST 59, ALT 62
Started Twinvir 1/15/16
6 wk. labs VL UND, AST 27, ALT 20
EOT labs VL UND, AST 23, ALT 19
SVR 16, VL UND, AST 28, ALT 17
SVR 24 , VL UND, 10/8/16
SVR 125, VL UND, 9/22/18
SVR 230, VL UND, 10/3/20
Last Edit: 5 years 2 weeks ago by Greedfighter.
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