Dear All, discussing with a statistician of a pharmaceutical company I received this answer about the statistical package that I have planned to use: As R is not a validated software package, we would like to ask if it would rather be possible for you to use SAS, SPSS or another approved statistical software system. Could someone suggest me a 'polite' answer? TIA Giovanni -- dr. Giovanni Parrinello External Lecturer Medical Statistics Unit Department of Biomedical Sciences Viale Europa, 11 - 25123 Brescia Italy Tel: +390303717528 Fax: +390303717488 email: parrinel@med.unibs.it [[alternative HTML version deleted]]
I like to know the answer as well. To be honest, I really have hard time to understand the mentality of clinical trial guys and rather believe it is something related to job security. On 6/8/07, Giovanni Parrinello <parrinel at med.unibs.it> wrote:> Dear All, > discussing with a statistician of a pharmaceutical company I received > this answer about the statistical package that I have planned to use: > > As R is not a validated software package, we would like to ask if it > would rather be possible for you to use SAS, SPSS or another approved > statistical software system. > > Could someone suggest me a 'polite' answer? > TIA > Giovanni > > -- > dr. Giovanni Parrinello > External Lecturer > Medical Statistics Unit > Department of Biomedical Sciences > Viale Europa, 11 - 25123 Brescia Italy > Tel: +390303717528 > Fax: +390303717488 > email: parrinel at med.unibs.it > > > [[alternative HTML version deleted]] > > ______________________________________________ > R-help at stat.math.ethz.ch mailing list > https://stat.ethz.ch/mailman/listinfo/r-help > PLEASE do read the posting guide http://www.R-project.org/posting-guide.html > and provide commented, minimal, self-contained, reproducible code. >-- WenSui Liu A lousy statistician who happens to know a little programming (http://spaces.msn.com/statcompute/blog)
Giovanni Parrinello wrote:> Dear All, > discussing with a statistician of a pharmaceutical company I received > this answer about the statistical package that I have planned to use: > > As R is not a validated software package, we would like to ask if it > would rather be possible for you to use SAS, SPSS or another approved > statistical software system. > > Could someone suggest me a 'polite' answer? > TIA > Giovanni >Search the archives and you'll find a LOT of responses. Briefly, in my view there are no requirements, just some pharma companies that think there are. FDA is required to accepted all submissions, and they get some where only Excel was used, or Minitab, and lots more. There is a session on this at the upcoming R International Users Meeting in Iowa in August. The session will include dicussions of federal regulation compliance for R, for those users who feel that such compliance is actually needed. Frank -- Frank E Harrell Jr Professor and Chair School of Medicine Department of Biostatistics Vanderbilt University
Cody_Hamilton at Edwards.com
2007-Jun-08 18:41 UTC
[R] "R is not a validated software package.."
Not to mention all the work that goes into PROC TEMPLATE and ANNOTATE to make SAS graphs presentable! I suspect that a lot of companies don't use SAS graphs or tables at all - they just export the data from SAS to Excel. -Cody Cody Hamilton, PhD Edwards Lifesciences What I would love to have is some efficiency estimates for SAS macro programming as done in pharma vs. using a high-level language. My bias is that SAS macro programming, which costs companies more than SAS licenses, is incredibly inefficient. Frank [[alternative HTML version deleted]]
On Fri, 2007-06-08 at 16:02 +0200, Giovanni Parrinello wrote:> Dear All, > discussing with a statistician of a pharmaceutical company I received > this answer about the statistical package that I have planned to use: > > As R is not a validated software package, we would like to ask if it > would rather be possible for you to use SAS, SPSS or another approved > statistical software system. > > Could someone suggest me a 'polite' answer? > TIA > Giovanni >The polite answer is that there is no such thing as 'FDA approved' software for conducting clinical trials. The FDA does not approve, validate or otherwise endorse software. If the pharma company in question has developed their own list of acceptable software applications that you must comply with, that is different, but is independent of any FDA requirements. As the saying used to be several decades ago, "Nobody ever got fired for buying IBM". In the clinical trials realm today, the same could be said for SAS or Oracle Clinical. That is a political, and perhaps a corporate legal counsel driven "risk aversion" based issue, not a scientific one. It is also a human behavioral issue, as Bert noted, relative to fighting inertia, training or re-training issues and the pre-existing investment in internal processes and infrastructure. This will change over time as more statisticians, who have been trained in the use of R during their academic years, enter into industry positions. As others have noted, there is a PERCEPTION that somehow SAS is endorsed by the FDA or that it constitutes a 'gold standard' of sorts. This is a perception and not reality. That being said: There are a variety of relevant Guidance and Guideline documents that the FDA has put forth to address these issues. Most recently, the FDA approved final guidance for the use of computerized systems in clinical investigations (May 2007): http://www.fda.gov/OHRMS/DOCKETS/98fr/04d-0440-gdl0002.pdf In addition, there is a General Principles of Software Validation document: http://www.fda.gov/cdrh/comp/guidance/938.html The majority of the 21 CFR Part 11 requirements (audit trails, electronic signatures, etc.) are relevant to systems that manage "source medical records". These would typically be database applications and medical devices, not statistical applications. In our shop for example, our Oracle 10g server has been implemented in accordance with these requirements. There is a 21 CFR Part 11 guidance document here: http://www.fda.gov/ohrms/dockets/98fr/5667fnl.pdf There are also all of the so-called FDA and ICH GxP (Good x Practice) documents: http://www.fda.gov/oc/gcp/guidance.html http://www.ich.org/cache/compo/475-272-1.html that provide a framework for operations in a regulated environment and for relevant statistical practice guidance. The 'x' above is replaced by words such as "Clinical", "Manufacturing", "Laboratory", etc. There is even a draft guidance document on the use of Bayesian techniques for medical device trials: http://www.fda.gov/cdrh/osb/guidance/1601.html Some of the references in other posts have to do with software embedded in medical devices, which could be anything such as bedside ECG monitoring stations, diagnostic imaging systems, radiation therapy instrumentation and pacemakers. These are generally not relevant to this discussion. The bottom line, is that while there is a burden on the part of the 'software publisher' to utilize and document reasonable manufacturing, version control, software maintenance and quality processes, the overwhelming burden is on the END USER to determine that their statistical package is suitable for the application intended and to have written SOPs (Standard Operating Procedures) to define how they will validate their installation and use of the statistical software. This goes to some of the comments that Cody had relative to IQ/OQ/PQ documentation, which refers to Installation Qualification, Operational Qualification and Performance Qualification. For example, in the context of R, the use of "make check-all" and the retention of the output subsequent to compiling R from source code can be part of that documentation process. Bert referred to this in his comments. Beyond that, the details of such documentation will be driven by a variety of characteristics that are relevant to the nature of the environment (academic, commercial, clinical, pre-clinical, etc.) in which one is operating and related considerations. As Frank noted, there will be a session at useR!2007: http://user2007.org/ entitled "The Use of R in Clinical Trials and Industry-Sponsored Medical Research". This session will take place on Friday, August 10 and I would invite any interested parties to attend the meetings. I think that you will find the subject matter quite enlightening. One closing comment: There is increasing use of R within the FDA itself and this will only further help to assuage the fears of prospective users over time. Best regards, Marc Schwartz
Cody_Hamilton at Edwards.com
2007-Jun-08 19:28 UTC
[R] "R is not a validated software package.."
The fact that FDA statisticians are using R also assuages one of the main concerns that I have heard voiced about using R for FDA submissions - that there would be no statisticians available at FDA to review R code which would seriously delay the review of a submission. Mark also brings up a good point by mentioning the FDA guidance on Bayesian submissions. If SAS were the only approved product, Bayesian trials would be in real trouble. Cody Hamilton, PhD Staff Biostatistician Edwards Lifesciences Disclaimer: As always, I am speaking for myself and not necessarily for Edwards lifesciences. One closing comment: There is increasing use of R within the FDA itself and this will only further help to assuage the fears of prospective users over time. Best regards, Marc Schwartz [[alternative HTML version deleted]]
On Friday 08 June 2007, Giovanni Parrinello wrote:> Dear All, > discussing with a statistician of a pharmaceutical company I received > this answer about the statistical package that I have planned to use: > > As R is not a validated software package, we would like to ask if it > would rather be possible for you to use SAS, SPSS or another approved > statistical software system. > > Could someone suggest me a 'polite' answer? > TIA > GiovanniYou can't validate any complex software package, i.e. computer programming language complexity (SAS, R, S-PLUS, SPSS, PERL, Python, Ruby, Java....) You can qualify a software package, and validate code written in it. As a "statistician" in a very large pharmaceutical company based in Basel which happens to be bigger than the other large pharma in Basel, I can say that we should have most of the paperwork done for qualification, at some point this year, for use as part of submission packages. Whether it will be used is another matter, which will be driven by business needs :-). So your colleague is right, only in the sense that whatever the company has approved is appropriate, and qualification in the "computer systems validation" context is expensive, time and man-power wise. But that holds true for any software package. Your colleague should have technically said: "As R is not a qualified software package at my company, we would like to ask if it would be possible for you to use software which my company has approved and done the /risk-management/ paperwork for and gotten approval from our Clinical Quality group to use". This is an issue -- however, whether R could pass that is not an issue, it clearly could be done if they wanted to do it. best, -tony blindglobe at gmail.com Muttenz, Switzerland. "Commit early,commit often, and commit in a repository from which we can easily roll-back your mistakes" (AJR, 4Jan05). -------------- next part -------------- A non-text attachment was scrubbed... Name: not available Type: application/pgp-signature Size: 189 bytes Desc: This is a digitally signed message part. Url : https://stat.ethz.ch/pipermail/r-help/attachments/20070609/4b620c21/attachment.bin