BNUMBER:  B-275277
DATE:  February 5, 1997
TITLE:  Bristol-Myers Squibb Company

**********************************************************************

Matter of:Bristol-Myers Squibb Company

File:     B-275277

Date:February 5, 1997

Robert J. Kenney, Jr., Esq., Thomas L. McGovern III, Esq., and S. 
Gregg Kunzi, Esq., Hogan & Hartson, L.L.P., for the protester.
Joel R. Feidelman, Esq., Deneen J. Melander, Esq., and C. Anthony 
Trambley, Esq., Fried, Frank, Harris, Shriver & Jacobson, for Merck & 
Company, the intervenor.  
Maura C. Brown, Esq., Philip S. Kauffman, Esq., and Phillipa L. 
Anderson, Esq., Department of Veterans Affairs, for the agency.
John L. Formica, Esq., and James A. Spangenberg, Esq., Office of the 
General Counsel, GAO, participated in the preparation of the decision.

DIGEST

1.  Price evaluation methodology, as reflected in the estimates set 
forth in a solicitation for drugs used in the treatment of 
hypercholesterolemia, is not objectionable where the protester fails 
to show that the methodology and estimates, which were in part the 
result of a statistical analysis, are not reasonably accurate, or are 
less accurate than the estimates would have been if they had been 
determined solely from the review of the agency's historical data.

2.  Protest of the relative importance of certain evaluation factors 
set forth in a solicitation for drugs used in the treatment of 
hypercholesterolemia is dismissed where the relative importance of the 
particular evaluation factors is a reflection of the agency's medical 
policy. 

DECISION

Bristol-Myers Squibb Company protests the terms of request for 
proposals (RFP) No. M5-Q6-96, issued by the Department of Veterans 
Affairs (VA), for hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase 
inhibitors.[1]  Bristol-Myers protests the RFP's price evaluation 
methodology as reflected in the estimates for the HMG-CoA reductase 
inhibitors and the relative importance of the RFP's evaluation 
factors.

We deny the protest.

This procurement is a part of VA's effort to standardize medical and 
pharmaceutical items to achieve concentrated buying power.  To assist 
in this effort, and to better manage its procurement of $1 billion of 
pharmaceuticals per year, the VA created a Pharmacy Benefits 
Management (PBM) section, which is staffed by Doctors of Pharmacy.  
The PBM is tasked with developing "evidence-based pharmacologist 
management guidelines for improving quality and providing best-value 
patient care."  The PBM section is guided in part by a Medical 
Advisory Panel (MAP), which is comprised of nine practicing VA 
physicians.  The pharmacologic treatment guidelines developed by the 
MAP provide guidance for standardized research-based care at all VA 
medical centers.

There are currently four HMG-CoA reductase inhibitors (also known as 
"statins") available in the United States for prescription.  They are 
pravastatin, produced by Bristol-Myers; lovastatin and simvastatin, 
produced by Merck & Company; and fluvastatin, produced by Sandoz.  
Because of their differing chemical compositions, the four statins 
differ as to efficacy in lowering low-density-lipoprotein (LDL) 
cholesterol.  The VA currently purchases varying quantities of each of 
the four statins for prescription by VA physicians to their patients.  

The MAP determined, based upon its review of the relevant medical 
literature and the needs of VA physicians, that two statins should be 
procured for use at VA medical centers, with one serving as "a 
first-line statin . . . designated as the preferred formulary agent," 
and a second statin as an alternate "for those [patients] who do not 
tolerate the preferred agent."  The MAP contemplates that once the 
primary and secondary statins are selected under this RFP, the agency 
will issue guidelines for converting all VA patients currently 
prescribed a statin (other than the statin selected as the primary 
statin) to the primary statin, and, for those patients who cannot be 
prescribed the primary statin, to the secondary statin.  For example, 
if a patient is currently prescribed a particular dosage of 
simvastatin, and pravastatin is selected as the primary drug for the 
treatment of hypercholesterolemia, that patient would be converted to 
pravastatin in accordance with MAP guidelines.        

The RFP provides for the award of two fixed-price requirements 
contracts, for a base period of 1 year with four 1-year options, for 
the supply of the two statins.  Consistent with the MAP's 
recommendations, one award will be made for the supply of one statin 
as the primary drug to serve an estimated 60 to 80 percent of VA's 
80,000 patients currently being treated with statins, and another 
award will be made for the supply of a secondary drug for treatment of 
the remaining 20 to 40 percent of patients who cannot use the primary 
drug.  

The RFP provides that offerors may submit offers to supply any of the 
four statins, and that award will be made to the offeror(s) whose 
proposal(s) represent(s) the best overall value to the government.  
The RFP states that technical merit is more important than price, and 
sets forth the following technical evaluation factors:  Safety, 
Efficacy, Outcome, Compliance, VA Patients, and Pharmacy.  The RFP 
states that the safety and efficacy evaluation factors are of equal 
importance, and each is more important than the outcome factor, and 
that the compliance and VA patients factors are of equal importance, 
and each is less important than the outcome but more important than 
the pharmacy factor.  The RFP provides detailed explanations for each 
of the evaluation factors; for example, the RFP explains that under 
the efficacy factor the agency will consider "the efficacy or 
reduction in LDL cholesterol levels which use of any drug yields," and 
under the outcome factor the agency will consider such matters as 
positive "reduction[s] in cardiovascular event rate[s] or 
mortalit[ies]" from the use of the drug.

The RFP requires the completion of a schedule of supplies and prices 
which differs depending on which of the four statins is offered.  For 
example, for pravastatin, per dose and extended prices are requested 
for an estimated 11 million 10 milligram (mg.) tablets, 21 million 20 
mg. tablets, and 18 million 40 mg. tablets; for simvastatin, prices 
are requested for an estimated 30 million 5 mg. tablets, 16 million 10 
mg. tablets, 3 million 20 mg. tablets, and 1 million 40 mg. 
tablets.[2]  The total evaluated price for each offer is the total of 
the extended prices.  

The RFP explains that the estimated quantities set forth in the 
schedule are "based on a scenario of converting all veteran patients 
currently taking [an] HMG-CoA [reductase inhibitor] to one of the 
competing agents."  For example, the estimated quantities set forth in 
the RFP for pravastatin or simvastatin are based upon VA's estimated 
requirements should it prescribe either pravastatin or simvastatin to 
all of its patients currently being treated with any of the four 
statins.  The process through which the agency determined its 
estimated quantities is detailed in the RFP. 
With regard to the estimated quantities set forth in the RFP, the MAP 
found that it could not project, based upon its past prescribing 
patterns for the four statins, its future requirements with any degree 
of reliability for the environment contemplated by this RFP--where on 
a national basis one statin will serve as the primary drug for 
treatment of patients with hypercholesterolemia, and another statin 
will serve as the secondary drug.  The VA explains that currently 
there is no standardized national formulary for the supply of statins, 
nor standardized protocol for the treatment of hypercholesterolemia 
with statins, and that because of this, its medical centers have 
different formularies and protocols for how statins are to be 
administered to VA patients.  

For example, the VA states that many of its medical centers use 
fluvastatin as the primary drug for treatment of hypercholesterolemia 
because it is currently the least expensive of the statins, and if a 
patient's cholesterol is not controlled by fluvastatin, the patient is 
administered the more potent lovastatin or simvastatin.  The agency 
adds here that because simvastatin has been prescribed by many of its 
medical centers primarily when treatment with a less potent statin has 
failed to produce the desired result of lowering LDL cholesterol, the 
prescribing patterns are skewed towards higher dosages of simvastatin.  
To illustrate this example, the chairman of the MAP points to the 
protocol of the VA's West Los Angeles medical center, which, depending 
on the desired cholesterol level, first treats patients with 10 mg. or 
20 mg. doses of pravastatin.  If the desired level is not achieved, 
the patient is prescribed 40 mg. doses of pravastatin, and if that 
treatment fails to produce the desired level, the patient is 
prescribed 20 mg. doses of the more potent simvastatin, or 40 mg. 
doses of simvastatin, depending on the success of the 20 mg. 
simvastatin treatment.  The result of this protocol, among other 
things, is that 5 mg. doses of simvastatin are "very rarely prescribed 
at [the] West Los Angeles" medical center.  The agency adds that each 
medical center's prescribing practices and the resulting prescribing 
patterns are also influenced by, among other things, the effectiveness 
of the various pharmaceutical manufacturers in marketing their 
products.
 
The MAP thus determined that it could best estimate its needs in an 
environment where one statin would be procured as the primary drug for 
treatment of hypercholesterolemia nationwide, and another statin as 
the secondary drug for such treatment, by considering, in conjunction 
with its current prescribing patterns, the relative potency of each of 
the statins.  With the assistance of a consultant, VA determined the 
potency of each of the four statins in the various dose amounts, in 
part through the performance of a statistical analysis of certain data 
as to the statins' relative efficaciousness.[3]  In performing its 
statistical analysis, the consultant analyzed 11 clinical studies 
provided by the agency,[4] setting forth a total of 47 dose-effect 
data points.[5]  From these 47 dose-effect data points, the consultant 
calculated three dose-effect data points each for fluvastatin and 
lovastatin, five dose-effect data points for pravastatin, and six 
dose-effect data points for simvastatin.  The consultant plotted these 
dose-effect data points on a graph where one axis represented the dose 
in mg. of statins and the other axis represented the effect of the 
dose in lowering LDL cholesterol by percentage.  The consultant then 
fit, with computer assistance, four different model curves for each 
statin, and determined for each statin which curve best fit the 
plotted dose-effect data points, considering the relative weight that 
each dose-effect data point should have on the analysis based upon the 
calculated precision of the data from which each dose-effect data 
point was derived.  From the selected logarithmic curves, dose-effect 
relationships were established for each of the statins.  For example, 
while there were differences between the curves depending on the 
dosages, simvastatin and lovastatin were determined to be, on average, 
3 times and 1.32 times more potent, respectively, than pravastatin.

This information was then converted by the agency, using a 
mathematical formula, to a comparative analysis of the commercially 
available doses for each of the statins with the presumption that all 
patients will be taking only one statin.  For example, the agency 
determined, based upon the foregoing statistical analysis of the 
clinical trials, that 6 mg. of simvastatin would have the same 
efficacy in lowering a patient's LDL cholesterol as 20 mg. of 
pravastatin.  Because simvastatin is only commercially available in 5 
mg., 10 mg., 20 mg., and 40 mg. doses (not 6 mg. doses), the agency, 
for price evaluation purposes, calculated that 80 percent of the 
patients currently taking 20 mg. of pravastatin would require 5 mg. of 
simvastatin, and 20 percent would require 10 mg. of simvastatin.  The 
agency then determined its requirements for each of the statins in the 
differing dose amounts, based upon the estimated dose equivalency 
ratios and the actual doses of the four statins dispensed by the VA to 
its patients in the first 6 months of 1996.  These estimates were 
included in the RFP schedule for pricing purposes.

Bristol-Myers protests that the RFP's price evaluation scheme, as 
reflected in the RFP's estimated quantities, is flawed to the 
prejudice of its product, pravastatin.  Bristol Myers attacks in some 
detail the statistical analysis performed by the agency to determine 
dose-effect relationships for each of the four statins, arguing that 
it "is so fundamentally flawed, both in concept and in execution, that 
it should not be used for any purpose."  The protester insists that 
because of this, the RFP's price evaluation methodology, and the 
resultant estimated quantities for each of the statins, must "be based 
on actual prescribing patterns, adjusted only on the basis of concrete 
empirical data on any likely changes in those patterns during the term 
of the contract."[6] 

Where estimates are provided in a solicitation, there is no 
requirement that they be absolutely correct; rather, they must be 
based on the best information available and present a reasonably 
accurate representation of the agency's anticipated needs.  
Lederle-Praxis Biologicals Div., Am. Cyanamid Corp., B-257104 et al., 
Aug. 22, 1994, 94-2 CPD  para.  205.  In this case, what we must therefore 
determine is whether the protester has shown that the agency's 
statistical analysis was flawed and that the data derived from the 
analysis is thus not reasonably accurate or is inaccurate to such an 
extent that the consideration of only VA's past prescribing patterns 
would have yielded more accurate estimates of the agency's needs.

The protester first points out that the analysis does not indicate 
"the selection criteria that were used to identify the studies on 
which the analysis was based," and concludes that from its review of 
the studies used that "the VA's selection criteria were invalid."  In 
this regard, the protester questions why the VA considered in its 
analysis only "multi-center" studies (studies where the same study 
protocol is followed at more than one research center), but not 
"single center" studies.  

While it is not disputed that the selection criteria by which various 
clinical studies were included or excluded in a statistical analysis 
is important, the protester has not identified any specific studies 
that were wrongfully included or not considered in the statistical 
analysis.  More importantly, the protester has not stated how or even 
if the data derived from the analysis would have been materially 
different if some of the studies used had been excluded and others 
included.  Thus, the agency's failure to specify its selection 
criteria does not provide a basis for our Office to find the analysis 
unreasonable.

The protester also contends that the consultant's statistical analysis 
is "useless" because it does not differentiate between comparative, 
within-study results, and non-comparative, across-study results.  That 
is, the consultant considered in his statistical analysis dose-effect 
data points for pravastatin and simvastatin which were derived from 
studies of the efficacy of pravastatin and simvastatin on a 
comparative basis as well as from studies which did not involve the 
comparison of the efficacy of the same two statins (e.g., a study of 
the efficacy of simvastatin and lovastatin).  Although we agree that 
it is generally accepted that, in the performance of an analysis like 
that done here, data derived from "within-study" comparisons of the 
relative efficacy of statins is preferable to that derived from 
"across-study" comparisons, the protester fails to demonstrate that 
because of this aspect of the consultant's methodology, the results of 
the analysis were not reasonably accurate.  Instead, the protester 
merely asserts that the methodology is inconsistent with VA's 
statement that comparative trials between statins should be the basis 
for the estimates included in the RFP, and that the methodology 
employed by the consultant renders the analysis "statistically 
invalid."

The protester disagrees with a number of other aspects of the 
statistical analysis (e.g., the derivation of the dose-effect curves, 
and the inversion of the dose-effect curves to obtain dosage 
equivalents), and points out that the analysis itself cautions that 
"no error analysis" has been done on the results and that estimating 
dose-effect relationships from a curve derived from only three known 
dose-effect data
points--as was the case with both fluvastatin and lovastatin--can be 
unreliable.  Again, while the statistical analysis sets forth a number 
of cautionary statements with regard to its results, the protester 
simply has not shown why these statements render the analysis 
"useless" or that the results of the analysis are not reasonably 
accurate.  Simply put, the protester, while pointing out that the 
conduct of the analysis was not an ideal "textbook" analysis, does not 
at any time provide any data indicating that had the analysis been 
performed in any other manner it would have yielded different 
results.[7]

The protester next argues that regardless of the methodology followed 
by the agency in performing the analysis, the results of the analysis 
must be in error because a number of published articles provide that 
simvastatin and lovastatin are, at most, two times and equally as 
potent, respectively, in lowering LDL cholesterol as pravastatin.  The 
agency responds that the articles cited by the protester do not 
demonstrate that the results of its statistical analysis are invalid 
and cites other articles that it asserts validates its analysis.  The 
agency points out, for example, that one of the articles cited by the 
protester does not describe the methodology or studies on which the 
article's conclusion, that 15 mg. of simvastatin is as potent in 
lowering LDL cholesterol as 20 mg. of pravastatin, is based.  The 
agency adds that this article was published in December 1993, and a 
number of clinical studies completed since then establish that 
simvastatin is considerably more potent than pravastatin in lowering 
LDL cholesterol than the articles reported 1.33 to 1 ratio.  Merck 
notes that some of the statements from the articles cited by the 
protester are out of context or are not based on valid clinical 
studies, and that none of these reports demonstrates that the agency's 
analysis is in error.  In our view, the articles referenced by the 
protester, agency, and intervenor evidence that there is considerable 
disagreement in the medical community as to the relative potency of 
the various statins, and, based on our review, we cannot conclude that 
these articles either invalidate the results of the agency's 
statistical analysis or validate the protester's view that simvastatin 
and lovastatin are at most two times as potent and equally potent, 
respectively, as pravastatin.[8]

The protester also argues that the estimates set forth in the RFP, and 
thus the results of the VA's statistical analysis, must be invalid 
because the estimates differ (in some instances greatly) from the VA's 
past prescribing patterns.  For example, the protester points out that 
60 percent of the RFP's estimated requirements for simvastatin are in 
the amount of 5 mg. doses, yet current data show that of all 
simvastatin doses dispensed by VA physicians, only 10 percent are in 
the amount of 5 mg.  The protester adds that on average, the RFP's 
estimates provide for an average simvastatin dose of 8.2 mg., in 
contrast with the average dose indicated by VA's past prescribing data 
of 16.2 mg., and an average dose of 25 mg. of pravastatin, as opposed 
to the past average pravastatin dose of 19.9 mg.

We think the differences in the average doses are to be expected, 
given that simvastatin is, according to the data and analysis provided 
by the agency and the protester, more potent than pravastatin, and 
given the agency's explanation of the protocols in prescribing statins 
followed by VA's various medical centers, which was affected by 
considerations other than the relative potency of the statins (e.g., 
cost, local marketing, or VA doctor or center preferences).  For 
example, the RFP contemplates, and the estimated schedule quantities 
are based upon, the presumption that if simvastatin is selected as the 
first line statin, the VA physicians, who are currently prescribing 
the less potent fluvastatin, lovastatin, or pravastatin to their 
patients, will convert those patients to the more potent simvastatin, 
rather than converting only those patients to simvastatin when the 
other statins fail to sufficiently lower the patients' LDL cholesterol 
as is reportedly being done under existing protocols.  The logical 
result of this practice would be to increase the number of doses of 
simvastatin in the lower dose amounts of 5 and 10 mg., and 
accordingly, the average dose of simvastatin prescribed by VA would be 
lower than that evident from past prescribing patterns.    

With regard to the protester's position that the RFP's estimates 
should be based solely upon the agency's historical data regarding its 
use of the statins, we agree with the agency that basing the estimates 
solely on such data would be inappropriate given the circumstances 
here.  We simply fail to see how historical data derived from VA's 
past prescribing patterns--given the VA's current policy of purchasing 
various quantities of each of all four of the statins and the 
differing treatment protocols of the varying medical centers--would, 
considered alone, result in accurate estimates of the agency's 
requirements in the environment contemplated by this RFP where there 
will be a standardized treatment protocol and only two statins 
available, with one designated as the primary drug for prescription.  
In short, we agree with the agency that the differing potencies of the 
statins is an appropriate consideration in determining its estimated 
requirements.  

Although the protester obviously disagrees with the agency's position 
as to the appropriate price evaluation and estimating methodology for 
this procurement, it has not shown the agency's determination in this 
regard to be unreasonable.  Specifically, the protester has not 
demonstrated that the statistical analysis did not yield reasonably 
accurate results or that a reliance on historical data alone would 
have produced more accurate estimates under the circumstances of this 
procurement.  As such, we cannot find that the resulting estimates in 
the RFP schedule were not based on the best information available or 
were not a reasonably accurate representation of the agency's 
anticipated needs.[9]  Id.

Bristol-Myers also protests the relative importance of the efficacy 
and outcome evaluation factors, arguing that a statin's ability to 
produce the desired outcomes of a reduction in cardiovascular event or 
mortality should be considered more important than a statin's efficacy 
in lowering LDL cholesterol levels, particularly since potency is 
being considered as part of the price evaluation.  Bristol-Myers 
argues in the alternative that the consideration of a statin's ability 
to produce positive outcomes should be considered under the efficacy 
evaluation factor, and not as a separate, less important, evaluation 
factor.

The agency explains that the MAP believes as a matter of medical 
policy that the safety associated with the use of the particular 
statins, and their relative efficacy in reducing LDL cholesterol 
levels, are more important in the treatment of hypercholesterolemia 
than the statins' abilities to produce certain other desired outcomes.  
The agency's determination here is a reflection of its medical 
policies and judgments, which we will not consider under our bid 
protest function.  IVAC Corp., 67 Comp. Gen. 531 (1988), 88-2 CPD  para.  
75; Travenol Labs., Inc., B-215739; B-216961, Jan. 29, 1985, 85-1 CPD  para.  
114.   

The protest is denied.

Comptroller General
of the United States

1. HMG-CoA reductase inhibitors are used in the treatment of 
hypercholesterolemia (i.e., high cholesterol).  

2. Prices are also solicited for various size packages of each of 
these statins.

3. The RFP schedule, as initially issued, was not based on this 
analysis.  It was developed after a Bristol-Myers's agency-level 
protest. 

4. The consultant initially considered 12 studies, but rejected one of 
the studies for inclusion in the statistical analysis because it 
lacked sufficient data to assess the relative precision of the study's 
results.

5. Each dose-effect data point represented the average percentage 
reduction in LDL cholesterol in patients who were administered a 
particular dosage of a particular statin.

6. It is unclear from the protester's submissions as to what "concrete 
empirical data on any likely changes" in the VA's prescribing patterns 
that it believes exists.   

7. The parties have submitted various comments on whether the analysis 
performed by the consultant was a proper or formal "meta-analysis."  
Since the protester has not shown that the analysis actually performed 
did not yield reasonably accurate results, there is no need to 
determine whether it was a properly conducted or formal 
"meta-analysis."  

8. While Bristol-Myers asserts that the principal article cited by the 
agency should be discounted because of its authors' ties with Merck, 
the protester has not shown that this article is either biased or 
clearly erroneous.

9. While the protester correctly notes that the RFP estimates are 
based upon 100-percent usage of the first line statin, even though the 
RFP contemplates only 60- to 80-percent usage and that a second line 
statin would also be selected, there is no suggestion that the 
relative percentages of the designated estimates for each dosage of 
each statin would be different; thus, this provides no basis to object 
to the evaluation scheme.