Appeals: Confirmed Referee Decisions : #110 - September 4, 2003

Decision of the Court having jurisdiction in the Class Action attached - May 19, 2006

D E C I S I O N

A. Introduction

[1] The Claimant applied for compensation as a Primarily-Infected Person pursuant to the Transfused HCV Plan ("the Plan").

[2] However, by letter dated November 18, 2002, the Administrator denied the claim, having carefully reviewed the material provided in support of the claim, along with a committee of three (3) senior evaluators, for the following reasons:

The results of your Traceback confirmed the donors of the blood transfused to you, during the class period, have tested negative for the HCV antibody. In light of this information, your claim was denied. You indicated in your response to our first letter that you would be sending in further evidence. In your case, as noted previously, no further evidence was received. Therefore, based on Article 3.04 of The 86-90 Hepatitis C Settlement Agreement, Transfused Plan, your claim is denied.

[3] By way of Request for Review by Arbitrator/Referee (the "Notice of Appeal") dated November 22, 2002, the Claimant requested a review of the denial of his claim by the Administrator.

[4] In paragraph 4 of his Notice of Appeal, the Claimant stated that he wished to review the Administrator's decision, for the following reasons:

After notification of approval, donors conveniently came forward after two years, on the day the cheque was to be forwarded to me. I find the sudden appearance of these donors was too convenient.

[5] The Claimant advised that he wished the matter to proceed by way of Reference and he requested an in-person hearing. A hearing date was initially scheduled for April 11, 2003. On April 11, 2003, the Claimant advised that he was unable to attend on that date and the hearing was therefore rescheduled for May 21, 2003.

[6] Fund Counsel's written submissions, dated April 9, 2003, set out the position of the Administrator. The Administrator concedes that the Claimant was hospitalized at St. Paul's Hospital in Saskatoon on December 22, 1999 for the purpose of undergoing a septorhinoplasty. Six units of blood were cross-matched and transfused. These submissions continue as follows:

[7] An in-person hearing was held in Saskatoon on May 21, 2003. The Claimant testified on his own behalf and Carol Miller, Appeals Coordinator of the Hepatitis C January 1, 1986 - July 1, 1990 Claims Centre (the "Claims Centre"), testified on behalf of the Administrator. In the result, the matter will indeed be adjudicated upon based on the written materials and testimony tendered by the parties, together with certain documentary materials obtained post-hearing, about which more will be said shortly.

B. Facts, Summary of Evidence

[8] Pursuant to the terms of the January 1, 1986 - July 1, 1990 Hepatitis Settlement Agreement ("the Settlement Agreement") and the Plan, the class period is the only period of time in respect of which compensation may be available. Further, while there are many possible sources of infection with respect to the Hepatitis C Virus ("HCV"), the Plan only provides compensation for individuals who received transfusions during the class period of defined blood products, the donors of which have been tested and found to be infected with the HCV.

[9] In the Claimant's General Claimant Information Form (TRAN 1) dated June 30, 2000, the Claimant stated that he believed that he was infected with the HCV through a Blood Transfusion received in Canada during the class period. He stated that he had received one Blood Transfusion in Canada during the class period and no transfusions before that. In his accompanying Declaration (TRAN 3) dated June 29, 2000 , the Claimant further declared it to be "true" that to the best of his knowledge, information and belief, he "was not infected with Hepatitis Non-A Non-B or the Hepatitis C virus prior to January 1, 1986". In Box 4 on TRAN 3, the Claimant checked off the "true" box beside the declaration that he "has never at any time used non-prescription intravenous drugs". The Treating Physician Form ("TRAN 2") was completed by the Claimant's physician, Dr. T., on June 13, 2000. Section F - Box 2 was checked off as "yes" following the statement: "Having regard to the definition of blood, the Claimant did receive a blood transfusion during the period January 1, 1986 to July 1, 1990." The physician added that this was "by history in 1989 - I do not have these records". The physician checked "no" in answer to the question: "Is there anything in the HCV Infected Person's medical history that indicates he or she was infected with Hepatitis Non-A, Non-B or the HCV prior to January 1, 1986?" In Section F, Box 1, with respect to whether the Claimant had a history of risk factors for the Hepatitis C virus other than a blood transfusion during the class period, the physician checked off the box indicating "none". This form also indicated that the physician had known the Claimant for 21 months.

[10] The twist in this case relates to the five-month report from the CBS to the Centre, dated April 6, 2001. This sets out the traceback results relative to the donors of the units of blood transfused to the Claimant, shows testing with respect to the donors of three of the six transfused units, each of whom was determined to be negative. However, there were no results shown with respect to the remaining three units. In one case, there was a notation: "letter received, no results submitted". In the remaining two cases, the notation simply indicates: "letter sent - no reply". In its second cover letter of April 6, 2001 to the Centre, the CBS states: "This traceback is deemed inconclusive." In the case of inconclusive results, where a transfusion of blood during the class period is established, the benefit of the doubt is provided to the Claimant. Given that status of matters, in April 2001, the Centre sent a letter to the Claimant enclosing a Full and Final Release, which was completed by the Claimant on May 1, 2001 and returned to the Centre on May 2, 2001. The claim was approved on the basis of disease level 3, as was a fixed payment of $57,283.21. While the Centre was in the process of requisitioning a cheque to be mailed to the Claimant, on May 12, 2001, CBS provided further information with respect to the traceback, which included supplementary information from CBS' regular traceback program. At this time, each of the three units in respect of which no information had previously been received, was now reported to have been traced back to negative donors. In light of this new information, as the cheque had not yet been forwarded to the Claimant, the Centre wrote to the Claimant to advise him that the previous approval of the claim, being based on an inconclusive traceback, was withdrawn and that it had now become necessary to deny the claim. The Claimant was invited to supply further evidence to refute these final traceback results. No additional documentary evidence was provided by the Claimant to the Centre with a view to refuting these results.

[11] In the CBS letter of May 12, 2001 to the Centre, a table was prepared which identified the unit number of each of the six units, along with the transfusion date, and listing the testing facility as CRCS, Sask. Health or Saskatoon District Health, after which the letter stated:

… The above unit numbers were input into CBS' Blood Information System ("BLIS database"), a computerized information system that tracks blood donor information. The BLIS database allows CBS to link unit numbers to the donors of those units. The donors associated with each of the above unit numbers were identified. It was determined that three of the donors associated with the above products were tested at the time of making subsequent donations. The other three donors were notified and submitted test results. ...

When testing on the donors associated with units A 722934-2 and A 722791-8 was conducted, the Canadian Red Cross Society ("CRCS") operated the blood system in Canada.

The screening test which CBS currently uses to detect the antibody to Hepatitis C is HCV 3.0 EIA which came into use in or about June 1996. Prior to that time, HCV 2.0 EIA was in use by CRCS. At the time of their use, each of these tests had been approved for use in Canada by Health Canada. For the purposes of its traceback program, CBS relies upon the HCV 2.0 EIA test and the HCV 3.0 EIA test.

For the purpose of its traceback program, CBS relies upon the results of anti-HCV testing conducted by testing laboratories external to CBS, namely Saskatchewan Health and Saskatoon District Health.
We have been informed by Saskatchewan Health that in 2001 at the time of testing of the donors associated with units A 726736-6 and A 726709-9 its laboratory was using the Abbott AxSYM HCV 3 version 1.00.1 immuno assay.

Saskatoon District Health has advised that in 1999 at the time of testing of the donor associated with unit A 726693-4, it was using the IMX HCV 3.0 immuno assay.

[12] Ms. Horkins tendered a Medical Information Update re: Hepatitis C from the Canadian Liver Foundation, which details possible sources of infection of HCV, together with the following statement: "In 10% of cases of hepatitis C, according to U.S. data, the source of the infection cannot be identified." She also supplied an article entitled "Enhanced surveillance of acute hepatitis B and C in four health regions in Canada, 1998 to 1999", Shimian Zou et al, Can J Infect Dis Vol 12 No 6 November/December 2001, in which at page 361 unknown source of infection is identified at 20.8%.

[13] At the outset of the in-person hearing, Ms. Horkins also tendered a copy of Reasons for Judgment of The Honourable Mr. Justice Pitfield of the British Columbia Supreme Court, released May 9, 2003, in the matter of Claim No. 1300593, which deals with the "reverse onus" or "notwithstanding" provisions contained in Article 3.04 of the Settlement Agreement. In fairness, Ms. Horkins invited the Referee and Claimant to take the time to review this decision before evidence was introduced, as it was her view that this case indicates that the Claimant must tender very persuasive evidence in order to successfully invoke this clause. In her view, the case requires the Claimant to bring in medical evidence for virtually all medical incidents during his lifetime, and that there was no onus on the Plan to chase down such information.

[14] In terms of viva voce testimony, Ms. Miller testified as to the process utilized to assess the Claimant's file, including the Claimant's obligation to establish both: (a) proof of receipt of blood products during the class period (here the Claimant was able to do so) and; (b) a Traceback producing a positive result (here the Claimant was unable to do so). She further testified as to the Traceback Protocol as approved by the Court. Sometimes a claimant obtains his or her own health records with the unit numbers recorded thereon, or the CBS can be asked to produce blood bank records. Tracebacks can only be conducted where a claimant has tested positive. The CBS can go into the system to access information about donors - e.g. are they HCV positive or not? If there are no records one way or the other, the CBS follows the donor and arranges for testing. Here, each of the donors was found to be HCV negative. Even though the tests were done as long ago as 1993 and as recently as 2001, the HCV antibody would still be in the donor's system if he/she had ever been tested positive. If the donor did not have the antibody at the time of testing, then the donor never had the virus before then. Ms. Miller referred to a letter from the Claimant's physician, Dr. T., dated May 28, 1998, which stated:

This gentleman received six units of packed cells following bleeding from surgery in December of 1989. He has no other known risk for Hepatitis C and recently at the request of the Red Cross, he was tested and found to be Hepatitis C antibody positive. If you require any further documentation of this, please feel free to contact me.

[15] Based on the PCR positive test and liver biopsy results, coupled with the information supplied to that point by the Claimant and his physician, given the inconclusive findings with respect to three of the six transfused units of blood, there was deemed to be sufficient proof for level 3 benefits and the claim was approved on that basis. Ms. Miller testified that the donors are not tested for the virus (which can be cleared or can come and go), but rather for the HCV antibody, which stays with you for life. In response to questions from the Claimant, Ms. Miller pointed out that testing for the virus only gives you a picture of what is going on with the donor on that day, whereas testing for the antibody reveals what the donor's condition was in the past. She further testified to the strict rules employed by CBS for tracebacks and the reliable GEN 2 or 3 testing approved by Health Canada. All testing done after 1996 is GEN 3. Ms. Miller further testified that in the event that any of the donors had not responded or not been tested, given the presumption in favour of the Claimant once a transfusion during the class period is established, the testing would have been deemed inconclusive and benefits would have been paid to the Claimant. The Litigation Notification Program (LNP) is complete within six months. It was Health Canada doing their traceback in May 2001, not the Centre, which resulted in this new information coming forward with respect to the three units in relation to which no answers had previously been provided. Once the Centre received information that all six donors had in fact tested negative, it was required to reject the claim. In response to further questions from the Claimant, Ms. Miller testified that even the 1993 testing procedures are considered reliable and there is no reasonable basis upon which to suggest that these donors tested in 1992 and 1994 should be re-tested, using GEN 3 testing. In response to questions from the Referee, Ms. Miller testified that there was a lot of bleeding as a result of the surgery in this case as six units of blood is a lot to be transfused.

[16] Next the Claimant testified. He was born in Ontario and grew up on a farm in the Ottawa valley. He used to drink but no longer does. He quit school at age 16 and became a construction worker. He moved to Saskatchewan about 25 years ago, when he as 23. He is presently employed as a grader operator for the R.M. in which he resides. He is no longer involved in farming. He did work for a period of years as a horse racetrack superintendent. He also worked in mining in northern Saskatchewan. In terms of medical history, he recalls having an appendectomy when he was nine years of age, in Ontario. He was a "normal teenager", having worked hard and played hard. He has had no tattoos, body piercing or intravenous drug use. When he was 17 or 18, he was involved in an accident that caused him to require 10-12 stitches on the back of his head. He has had the odd broken arm, but nothing that required extended hospital stays. The only time he has taken off work was for back injuries. He is married with two children, ages 20 and 17, each of whom is in good health, except one has a bone disorder. His wife has been tested and does not have HCV. He did have other sexual partners prior to marrying his spouse 20 years ago, but no partners other than her since. He is not aware of anyone in his circle of friends, family or people he has had contact with who had HCV. He had never heard of HCV until he received his letter asking him to go in for testing, in 1999. His present health is good. He has had regular inoculations and referred to the Saskatoon medical clinic that he has attended at. He described the unfortunate incident in December 1989, which required him to undergo the surgery that caused him to require the six units of blood. He got beaten up badly at a party and his nose was smashed. Since that surgery, his medical history has consisted of an injury to his foot as well as minor injuries such as twisted ankles or feet. He also got hit on the head while working in 1996 or 1997, and lost 17 teeth, which caused him to be stitched up, but he only missed a few hours of work as a result. He also had two wisdom teeth extracted four or five years ago. He believes that his g. p prior to Dr. T transferred all his records to Dr. T. His infectious disease specialist has not offered any views as to how he feels that the Claimant contracted HCV, but did say that there were ways other than blood transfusions. Under questioning from Ms. Horkins, the Claimant acknowledged that he had been briefly incarcerated, no longer than overnight, for alcohol-related driving offences, once or twice.

[17] At the conclusion of the hearing, there was discussion surrounding the Claimant's medical background. Given the nature of the surgery, which occurred within the class period, and the multiple units of blood that were transfused to the Claimant, in order to leave no stone unturned in considering the Claimant's claim for benefits, it was felt by the Referee that steps should be taken to obtain at least the complete health record for the Claimant in the possession of Dr. T., which would presumably also include the records from the physician that the Claimant had attended on previously. Depending on what was revealed from these records, either party might find it advisable to tender or request further records. Further, Ms. Horkins indicated that she may wish to file further submissions with respect to the reliability of the GEN 2 and GEN 3 testing.

[18] The Referee wrote to Dr. T. on May 29, 2003 as follows:

Please be advised that I am the appointed Referee with respect to the determination of (Claimant's) claim for entitlement to certain benefits.

For the purpose of assisting me in determining the matter, I would appreciate receiving copies of your complete office chart and clinical record for (Claimant), including correspondence sent and received, including any chart material that was forwarded to you by (Claimant's) previous physician. I am not requesting a medical/legal report at this time.

I am enclosing (Claimant's) consent to enable you to release this information to me. Further, I undertake to honour your reasonable copying and postage charges.

Thank you for your assistance in this matter.

[19] Dr. T. supplied his chart on June 9, 2003, copies of which were forwarded on the same date to the Claimant and to Ms. Horkins, along with the request that the parties notify the Referee by June 26, 2003, if they intended to request or provide further medical information. This chart has been received in evidence as Exhibit 2, as if it had been tendered at the hearing. Having reviewed this chart, it appears that the Claimant was mistaken in his understanding that his previous physician's chart had been forwarded to his present physician, Dr. T. The chart describes some of the ankle and other injuries described by the Claimant. It also refers to foreign objects that had been removed from the Claimant's eye in 1996 or 1997, with resulting corneal scaring. There is a 1998 report from a Saskatoon Infectious Disease specialist, confirming that the Claimant's spouse had tested negative for the HCV antibody. Unfortunately, the chart does not contain records prior to the Claimant first attending on Dr. T. The Claimant did not file any further materials, such as prior health records, nor did he request time to do so, or assistance from the Referee in doing so.

[20] Under cover of letter dated June 13, 2003, Fund Counsel provided a copy of a letter dated May 30, 2003 from Lindsay Patterson, Manager, Transfusion Medicine Programs, CBS to Carol Miller, Appeals Co-ordinator, 86-90 Hepatitis C Claims Centre. The letter from CBS has been received in evidence as Exhibit 3, as if it had been tendered at the hearing. This letter states:

You have asked CBS to provide you with additional information on the donors associated with the units transfused to the above-noted claimant.

In fulfilling its obligation to provide traceback information to the Fund Administrator, CBS will not compromise the rights of privacy of its donors in respect of their personal information. CBS has obligations to protect the privacy of its donors and has entrenched the principles in its Freedom of Information and Protection of Personal Information Policy.

CBS' donors expect CBS to keep their personal information confidential. The sufficiency of the blood supply would be threatened if CBS violated the donors' rights to privacy, as these volunteers would likely stop donating blood.

On the other hand, CBS recognizes that the result of CBS' traceback investigation in this case was a factor considered by the Fund Administrator in making its decision and that as such, the investigation is under scrutiny in the Appeal.

Health Canada requires that CBS and the Canadian Red Cross Society ("CRCS") before it, permanently defer any donor from donating blood in future, who has had a reactive test for Hepatitis C Antibody ("anti-HCV"), whether or not that donor tests positive or negative on confirmatory testing. As you are aware, CRCS had implemented the first generation of anti-HCV testing (EIS 1.0) by July, 1990 and the second generation of anti-HCV testing (EIZ 2) in June, 1992.

Outlined below is a list which indicates the number of times donations were made by the specific donors associated with the unit numbers in question.

[21] On August 12, 2003, the Referee received a letter from Ms. Horkins dated August 5, 2003, which provided a report from Dr. Steven Kleinman dated August 5, 2003. This was provided for the purpose of assisting the Claimant in his understanding of the reliability of donor testing regardless of whether EIA 2 or 3 is used. Ms. Horkins stressed her position that the Administrator was making Dr. Kleinman's report available notwithstanding that the Administrator has no obligation to prove the reliability of these tests, which are incorporated into the court approved traceback procedure. Dr. Kleinman's report has been received in evidence as Exhibit 4, as if it had been tendered at the hearing. Rather than paraphrasing Dr. Kleinman's report, it is appended in its entirety to this decision. The Referee wrote to both parties on August 14, 2003, inviting the Claimant to forward any additional materials or submissions he may have by August 28th, and informing the parties that the decision would be prepared based on the materials in hand by that date. The Claimant did not make any further submissions.

C. Analysis

[22] The following are the material findings of fact in this case:

(a) The Claimant is infected with Hepatitis C.

(b) The probable source of such infection was not established in evidence.

(c) Although the Claimant was transfused with six units of packed Red Blood Cells at St. Paul's Hospital, Saskatoon, in December 1989, the Traceback showed that in each case, the donor had tested negative for the HCV, using the most advanced testing available at the applicable time, namely HCV EIA 2.0 and 3.0 respectively.

(d) The Claimant did not receive any blood products while hospitalized either before or after the December 1989 surgery.

(e) Accordingly, while the Claimant has established that he received a transfusion of blood products in Saskatoon during the class period, he was unable to establish that any of the donors of such products was infected with the virus.

[23] There is no evidence to suggest that the Administrator did not follow the Court Approved Protocol containing the Criteria for Traceback Procedures for Primarily Infected Persons. Having done so, it was then obligated to apply the provisions of the Plan text, which provide:

[24] In this regard, the Referee is mindful of other decisions which bear on this issue, including:

[25] Fund Counsel candidly acknowledged that there have been no Arbitrator/Referee or Court cases to date that have allowed a Claimant to "prove that he was infected with HCV by a Blood transfusion received in Canada during the class period, notwithstanding the results of the Traceback Procedure".

[26] It is necessary to give careful consideration to the decision of Mr. Justice Pitfield in HCV Settlement Agreement Claim No. 1300593, 2003 BCSC 739. The following paragraphs are particularly germane to the issues under consideration in the present case:

[27] In argument, Ms. Horkins was invited to advise as to her position as to what circumstances could meet the "persuasive objective evidence" approach set out by Justice Pitfield. It was her view that an example might be where a claimant had received only one donation of blood, with a completely clean medical history supported by thorough medical evidence, in which signs of infection, such as jaundice or elevated liver function tests, showed up shortly after the transfusion. It was acknowledged that some people do show signs of acute HCV, but not everyone does. In addition, the Claimant would have to provide a complete medical history that would show an absence of opportunity to be infected from other sources.

[28] In this case, the Referee did initiate the post-hearing process of obtaining additional medical information in order to ensure that no stone would be left unturned in ensuring that the Claimant's position that he was entitled to benefits was exhaustively explored. Concerns were raised at the hearing as to the reliability of the GEN 2 testing as well as with respect to the number of units or transfused blood received, each one in theory increasing the risk of transmission of HCV. However, regrettably for the Claimant, the file material from Dr. T. did nothing to assist the Claimant in advancing his position as there was no evidence from the numerous hospitals and physicians that the Claimant had attended on earlier in his life. There was evidence of a prior appendectomy and other opportunities for infection, although no definitive source of infection was established in evidence. The May 30, 2003 letter from CBS, summarizing multiple donations on the part of four of the six donors, and in particular 22 and 24 donations respectively from each of the donors tested with GEN 2 testing, will hopefully allay some of the Claimant's concerns. Nevertheless, they do further bolster the reliability and validity of the application of the traceback procedure in this particular case.

[29] In conclusion, there was simply no persuasive contradictory medical or other evidence adduced by the Claimant that could meet the Pitfield test, in order to allow a Referee to conclude that the Claimant had "refuted the results of the traceback procedure".

[30] This result must be particularly frustrating and upsetting for the Claimant in that, not only did he establish that he received blood products during the class period while hospitalized at St. Paul's Hospital in Saskatoon in December 1989, but he was in fact also able to establish that blood products were in fact transfused to him, and finally he had been advised that his claim had been approved. Had it not been for the 11th hour evidence supplied by the CBS, he would have received his initial payment and been approved for the claim. However, regrettably for the Claimant, in the final analysis, he was unable to establish that the packed blood cells received at St. Paul's Hospital were infected with the HCV. The number of units of transfused blood, coupled with the fact that there were six separate donors, only served to justifiably heighten the Claimant's belief that there had been an error in the donor testing. There is indeed some initial merit to the Claimant's contention that the chances of error increased with each additional donor. Given the number of separate donors involved in this case, had the testing been GEN 1, the Claimant's arguments would have had greater strength. However, given the combined weight of the uncontradicted submissions of Dr. Kleinman as to the reliability of both GEN 2 and GEN 3 testing, the May 30, 2003 CBS letter, the numerous tests on many of the donors and the court-approved traceback framework, the Claimant's position cannot prevail.

[31] The Claimant's evidence was provided in a most candid and straightforward manner. There is no basis to doubt the sincerity of his belief that he contracted HCV as a result of the St. Paul's Hospital transfusions. Nevertheless, there was inadequate evidence adduced to meet the test enunciated by Justice Pitfield, so as to allow the findings from this process to be disturbed. The Referee is satisfied that the Centre was not looking for ways to deny the Claimant's claim, but was to the contrary co-operating fully in ensuring that all avenues of compensation available to the Claimant pursuant to the Plan would be fully explored. While the manner in which events unfolded was understandably troubling to the Claimant, the fact that the cheque was requisitioned further demonstrates the bona fides of the Centre in the administration of this claim.

[32] The appeal must fail. The Claimant is not entitled to receive compensation. The Administrator has an obligation to assess each claim and determine whether or not the required proof for compensation exists. The Administrator has no discretion to allow compensation where the required proof does not exist. The financial sufficiency of the Fund depends upon the Administrator properly scrutinizing each claim and determining whether the Claimant qualifies. A Referee similarly has no jurisdiction to alter, enlarge or disregard the terms of the Settlement Agreement or Plan, or to extend or modify coverage, including the reverse onus contained in Section 3.04(2) of the Plan text.

D. Decision

[33] Upon careful consideration of the Settlement Agreement, Plan, Court orders and the viva voce and documentary evidence tendered, the Administrator's denial of the Claimant's application for compensation is hereby upheld.

Dated at Saskatoon, Saskatchewan, this 4th day of September 2003.

________________________________
DANIEL SHAPIRO, Q.C., C. Arb.
Referee

Report of Dr. Steven Kleinman to Fund Counsel
Hepatitis C antibody testing of blood donors
August 5, 2003

My qualifications for rendering an opinion on Hepatitis C antibody testing of blood donors are as follows:

· Specialized training in the field of Transfusion Medicine (blood banking), including certification in this discipline by the American Board of Pathology.

· Previous job responsibilities including Medical Director of the American Red Cross Blood Services, Southern California region and the Co-Director of Transfusion Medicine at UCLA Medical Center.

· Special expertise in the field of transfusion-transmitted infection as evidenced by seven years of experience in chairing the American Association of Blood Banks Transfusion Transmitted Disease Committee, my participation as a principle investigator in several large-scale, US government sponsored research studies on transfusion-transmitted infections, and my publication of numerous peer reviewed scientific articles and book chapters on transfusion-transmitted infections and diseases (including Hepatitis C).

Hepatitis C antibody testing

The hepatitis C (also abbreviated as HCV) antibody test has been licensed for both blood screening and diagnostic uses by Health Canada. Several versions of the test have been licensed including version 1 or ELISA 1 (introduced for blood donor screening in Canada about July 1990), version 2 or ELISA 2 (introduced about July 1992), and version 3 or ELISA 3 (introduced about June 1996).

The first version of the hepatitis C antibody test (designated ELISA 1) utilized a single hepatitis C recombinant protein. The second version of the antibody assay (ELISA 2) included several additional hepatitis C proteins in the test system, thereby permitting detection of antibodies against several viral gene products rather than only against one viral antigen. The third version of the antibody assay (ELISA 3) has one additional antigen and has reformulated some of the antigens used in the ELISA 2.

Data concerning the performance of the ELISA 2 compared to the ELISA 1 indicate significantly enhanced sensitivity by use of the ELISA 2. Several different sources of data indicate that the ELISA 1 test detected only 60 to 80% of the hepatitis C infections detected by ELISA 2. [1,2]

In contrast to the ELISA 1, there are numerous reports documenting the high sensitivity of both the ELISA 2 and ELISA 3 assays for detecting Hepatitis C infection. [2-7] Some articles report test sensitivities of 100% [2,3] while others indicate that the sensitivity of ELISA 3 is slightly higher than that of ELISA 2. [4]
It has been extremely difficult to precisely determine the sensitivity of the ELISA 2 and ELISA 3 assays because their performance is so similar and because there is no gold standard for the diagnosis of HCV infection. Different studies report slightly different sensitivities for these assays; the sensitivity reported in the literature for each of these ELISA versions will vary depending on the population in which the tests have been evaluated. Consequently, most review articles do not provide direct comparisons between the sensitivity of the ELISA 2 or ELISA 3, but rather state that their sensitivities are relatively equivalent. Furthermore, the FDA product inserts for both of these assays do not report assay sensitivity, presumably because of the lack of an accurate method by which to measure it.

The basic consensus of these reports is that there are only very small differences in performance of the ELISA 3 versus ELISA 2. Data concerning the performance of the ELISA 3 compared to the ELISA 2 indicate a slight improvement in sensitivity in specific testing scenarios. There is increased sensitivity in early hepatitis C infection (earlier detection of seroconversion in some patients), improved detection of antibody in immunosuppressed patients, improved specificity (fewer false positive results), and a slightly better sensitivity in detecting antibody in chronic infection. In conclusion, the published literature supports the fact that experts in the field agree that both the ELISA 2 and ELISA 3 assays have high sensitivity for diagnosing Hepatitis C infection.

Two recent studies have investigated specific aspects of ELISA 2 and ELISA 3 performance in populations of blood donors. [8, 9] The first study is relevant to transmission of HCV by blood transfusion; i.e. how frequently will the ELISA 3 test detect a donor who tests negative by the HCV ELISA 2 test and who has HCV virus in the blood (and is therefore potentially infectious). The study is based on testing of 5.5 million donations at 13 US blood centers after introduction of routine HCV RNA testing in donor screening in 1999. [8] The investigators determined that this phenomenon occurs at a rate of approximately 1 in 200,000 donations. The interpretation of these data is that prior to the introduction of HCV RNA screening in 1999, there would be one instance in 200,000 transfusions where HCV ELISA 2 testing would have permitted HCV infection to occur whereas HCV ELISA 3 testing would have prevented it. These data point to the slight increase of blood safety that occurred with introduction of ELISA 3 testing. However, these data are not directly applicable to the issue of the use of ELISA 2 vs ELISA 3 testing in traceback investigations.

The second study addresses the issue of the ability of the two assays to detect past HCV infection in blood donors. In this study, 501 donations (out of a total of approximately 292,000 ELISA-3 tested donations) that were confirmed antibody positive by ELISA 3 at the time this assay was initially introduced into blood donor screening were retested using the ELISA 2. [9] The authors found that 15 of these 501 donations (2.99%) were negative by ELISA 2; the ELISA 2 detected >97% of ELISA 3 positive donations. In other words, in the situation in which a blood donor had HCV antibody demonstrated by ELISA 3, the antibody was not detected by ELISA 2 in only 3% of the cases. This study differed from the first study reported above in that all 15 of the ELISA 3 positive/ELISA 2 negative results were in HCV RNA negative donors who would be highly unlikely to be infectious for HCV.
Caution should be exercised in how the data from the latter study described above are extrapolated to the traceback scenario, since traceback is a different circumstance than the question explored in that study. The statement that if the ELISA 3 is positive, the ELISA 2 will be negative 3% of the time (which is the conclusion of the blood donor screening study described above) is not equivalent to the statement that if the ELISA 2 is negative, then the ELISA 3 will be positive 3% of the time. This latter is the situation that we are asked to evaluate in traceback cases with negative ELISA 2 results. In my opinion, a negative ELISA 2 test in a traceback investigation would be much more likely to represent lack of HCV antibody as opposed to antibody only detectable by ELISA 3. Therefore, I believe that the 3% difference in detection reported in the blood donor screening study represents the maximum likelihood of this occurrence in the traceback scenario. However, it is highly likely that the probability that an ELISA 2 negative traceback result would be ELISA 3 positive is much less than 3%.

A recent summary of the performance of currently used HCV antibody tests by a recognized HCV testing expert was presented at a US National Institutes of Health Consensus Conference: Management of Hepatitis C: 2002. Concerning HCV antibody EIAs (EIA and ELISA are two different abbreviations for the same assay), the speaker wrote "Anti-HCV is typically detected using second or third generation enzyme immunoassays that detect mixtures of antibodies to various HCV epitopes. The specificity of currently available EIAs for anti-HCV is higher than 99%. Their sensitivity is more difficult to determine in the absence of a more sensitive gold standard. EIAs for anti-HCV detect antibodies in more than 99 percent of immunocompetent patients with detectable HCV RNA." [5] In other words, HCV infection can be diagnosed successfully using ELISA tests in 99 cases out of 100. This is extremely high performance for a laboratory assay.

References

1. Alter HJ. New kit on the block: evaluation of second-generation assays for detection of antibody to the hepatitis C virus. Hepatology 1992: 15:350-353

2. Bresters D, Cuypers HTM, Reesink HW et al. Enhanced sensitivity of a second generation ELISA for antibody to Hepatitis C virus. Vox Sang 1992; 62:213-217

3. Vrielink H, Zaaijer HL, Reesink HW et al. Sensitivity and specificity of three third-generation anti-hepatitis C virus ELISAs. Vox Sang 1995; 69:14-17

4. Gretch DR. Diagnostic tests for hepatitis C. Hepatology 1997; 26 (Suppl.1): 43S -
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5. Pawlotsky JM. Use and interpretation of virologic tests. NIH Consensus Conference: Management of Hepatitis C: 2002 abstract program book available on the Web at http://consensus.nih.gov/cons/116/1l6cdc_ intro.htm

6. Courouce AM, Barin F, Botte C et al. A comparative evaluation of the sensitivity of seven anti-hepatitis C virus screening tests. Vox Sang 1995; 69:213-216

7. Germer JL, Zein NN. Advances in the molecular diagnosis of Hepatitis C and their clinical implications. Mayo Clinic Proc 2001; 76:911-920

8. Galel SA, Strong DM, Tegtmeier GE et al. Comparative yield of HCV RNA testing in blood donors screened by 2.0 versus 3.0 antibody assays. Transfusion
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9. Impact of HCV 3.0 EIA relative to HCV 2.0 EIA on blood donor screening. Tobler LH, Stramer SL, Lee SR et al. Transfusion 2003 (in press)

Dr. Steven Kleinman
Clinical Professor of Pathology
U. British Columbia
Vancouver, B.C.

J U D I C I A L D E C I S I O N

Judge Winkler's Decision - May 19, 2006