ASTM F3108-19

This international standard was developed in accordance with internationally recognized principles on standardization established in the Decision on Principles for the
Development of International Standards, Guides and Recommendations issued by the World Trade Organization Technical Barriers to Trade (TBT) Committee.
Designation: F3108 − 19
Standard Guide for
Clinical Outcomes for Clinical Trials and/or Clinical
Registries for Knee Reconstructive Surgery
This standard is issued under the fixed designation F3108; the number immediately following the designation indicates the year of
original adoption or, in the case of revision, the year of last revision. A number in parentheses indicates the year of last reapproval. A
superscript epsilon (´) indicates an editorial change since the last revision or reapproval.
1. Scope mendations issued by the World Trade Organization Technical
Barriers to Trade (TBT) Committee.
1.1 This guide is intended as a resource for individuals and
organizations when designing clinical trials and/or clinical
2. Referenced Documents
registries and addresses the selection of patient-reported
2.1 ASTM Standards:
outcomes,safetyoutcomes,imagingoutcomesandothertopics
F561 Practice for Retrieval and Analysis of Medical
related to knee reconstructive surgery (KRS) including: (1)
Devices, and Associated Tissues and Fluids
knee replacement systems, (2) anterior cruciate ligament
F2809 Terminology Relating to Medical and Surgical Mate-
reconstruction, (3) knee meniscus implants or tissue engi-
rials and Devices (Withdrawn 2019)
neered medical products (TEMPs), (4) articular cartilage im-
F2979 Guide for Characterization of Wear from the Articu-
plants or TEMPS, (5) peri-articular knee osteotomies, (6)
lating Surfaces in Retrieved Metal-on-Metal and other
peri-articular knee fractures (including distal femur, patella,
Hard-on-Hard Hip Prostheses
and proximal tibia fractures), or other knee surgeries.
2.2 ISO Standards:
1.2 In this guide, methods to measure the efficacy,
ISO 12891-1 Retrieval and analysis of surgical implants –
effectiveness, and safety of KRS devices through standardizing
Part1: Retrieval and handling
clinical outcome measures are provided for designing,
ISO 12891-2:2014 Retrieval and analysis of surgical im-
reviewing, and accepting human clinical trial protocols.
plants – Part 2: Analysis of retrieved surgical implants
1.3 This guide is intended to provide consistency in study
design, review, regulatory approval, and health insurance
3. Terminology
coverage approval for knee reconstructive surgery to the health
3.1 Definitions:
care market.
3.1.1 level of evidence, n—strength of clinical evidence for
1.4 For the purpose of this guide, KRS pertains to any
evidence-based medicine (1).
device or TEMP that is intended to replace, resurface,
3.1.2 safety, n—the condition of being protected from or
reconstruct, and/or provide fixation of the knee joint, in part or
unlikely to cause risk or injury.
in total, as a treatment for joint disease, trauma, or dysfunction,
3.2 Acronyms:
where long-term improvement in function and pain relief
3.2.1 AAHKS—American Association of Hip and Knee
without major adverse events are the desired outcomes.
Surgeons
1.5 This standard does not purport to address all of the
3.2.2 AAOS—American Academy of Orthopaedic Surgeons
safety concerns, if any, associated with its use. It is the
responsibility of the user of this standard to establish appro- 3.2.3 ACL—anterior cruciate ligament
priate safety, health, and environmental practices and deter-
3.2.4 AJRR—American Joint Replacement Registry
mine the applicability of regulatory limitations prior to use.
3.2.5 ASA—American Society of Anesthesiologists
1.6 This international standard was developed in accor-
dance with internationally recognized principles on standard-
ization established in the Decision on Principles for the 2
For referenced ASTM standards, visit the ASTM website, www.astm.org, or
Development of International Standards, Guides and Recom- contact ASTM Customer Service at service@astm.org. For Annual Book of ASTM
Standards volume information, refer to the standard’s Document Summary page on
the ASTM website.
The last approved version of this historical standard is referenced on
This guide is under the jurisdiction of ASTM Committee F04 on Medical and www.astm.org.
Surgical Materials and Devices and is the direct responsibility of Subcommittee Available from American National Standards Institute (ANSI), 25 W. 43rd St.,
F04.39 on Human Clinical Trials. 4th Floor, New York, NY 10036, http://www.ansi.org.
Current edition approved April 1, 2019. Published May 2019. DOI: 10.1520/ The boldface numbers in parentheses refer to the list of references at the end of
F3108-19. this standard.
Copyright © ASTM International, 100 Barr Harbor Drive, PO Box C700, West Conshohocken, PA 19428-2959. United States
F3108 − 19
3.2.6 CAT—Computer Adaptive Testing 4. Summary of Guide
3.2.7 CDRH—Center for Devices and Radiologic Health
4.1 It is the intent of this guide to provide an overview of
appropriateoutcomesthataretobeaddressedinhumanclinical
3.2.8 CMS—Centers for Medicare & Medicaid Services
trials of knee reconstructive surgery (KRS). Depending on the
3.2.9 EQ-5D—European Quality of Life – 5 Domains
requirements of the clinical trial, the outcomes to be addressed
3.2.10 FDA—Food and Drug Administration
include knee-specific patient-reported outcomes, health-related
3.2.11 HRQL—Health-related quality of life quality-of-life patient-reported outcomes, activity level scales,
pain relief (i.e., VAS, NPRS), and adverse events collection
3.2.12 ICD—International Classification of Diseases
and reporting.
3.2.13 IKDC—International Knee Documentation Commit-
4.2 Because of the broad range of indications for KRS,
tee
patient comorbidities, and functional/activity levels, it is im-
3.2.14 KOOS—Knee injury and Osteoarthritis Outcome
possible to identify or specify a single instrument score that
Score
measuresthe“success”ofKRS.Instead,aclinicallysignificant
3.2.15 KOOS JR—Knee injury and Osteoarthritis Outcome
improvement (minimum clinically important difference
Score Joint Replacement
[MCID]) in a joint-specific, disease-specific, or quality-of-life
3.2.16 KRS—Knee Reconstructive Surgery
instrument should be used as a measure of clinical “success”
(2). Clinical success measured with patient-reported outcomes
3.2.17 KSS—Knee Society Score
may be defined through clinical improvement in terms of
3.2.18 LEAS—Lower Extremity Activity Scale
MCIDs and/or achieving a clinical success threshold value
3.2.19 MCID—Minimum clinically important difference
defined and justified in the study protocol or literature. The
MCID can be calculated using consensus methods (also known
3.2.20 MDC—Minimum detectable change
as Delphi method), anchor-based methods, and distribution
3.2.21 MOON—Multicenter Orthopaedic Outcomes Net-
methods. Consensus methods use clinical and domain experts
work
to define the MCID (3).Anchor-based approaches compare the
3.2.22 MRI—Magnetic Resonance Imaging
change in the patient-reported outcome (PRO) score to some
3.2.23 NPRS—Numeric Pain Rating Scale other measure of change, considered an anchor or external
criterion, to determine whether or not a magnitude of change is
3.2.24 OKS—Oxford Knee Score
significant. The anchor may consist of a clinical measure or a
3.2.25 PRO—Patient-reported outcome
Global Assessment Rating in which the patients rate them-
3.2.26 PROMIS—Patient-Reported Outcomes Measurement
selves to some extent as ‘‘better,’’ ‘‘unchanged,’’ or ‘‘worse.’’
Information System
Distribution-based approaches compare the change in PRO
scorestosomemeasureofvariabilitysuchasthestandarderror
3.2.27 QALY—Quality Adjusted Life Year
ofthemean(SEM),thestandarddeviation(SD),theeffectsize,
3.2.28 RSA—Radiostereometric analysis
or the minimum detectable change (MDC) (4).Although there
3.2.29 SAE—Serious adverse event
is no consensus as to the superior method to determine the
MCID, it is recommended that the MCID be based primarily
3.2.30 SD—Standard deviation
on relevant patient-based and clinical anchors. Distribution-
3.2.31 SEM—Standard error of the mean
based methods should be used to support the estimates from
3.2.32 SF-6D—Short Form (6 dimensions)
anchor-based approaches and can be used in situations where
3.2.33 SF-12—Short Form (12 questions) anchor-based estimates are unavailable (5). Whenever
possible, investigators should use validated scores with estab-
3.2.34 SF-36—Short Form (36 questions)
lished MCID values.
3.2.35 TEMP—Tissue Engineered Medical Products
(ASTM Subcommittee F04.40) 4.3 The application of this guide does not guarantee clinical
success of a finished product but will help to ensure consis-
3.2.36 TKA—Total Knee Arthroplasty
tency and adequacy of the data collected based on the clinical
3.2.37 UKA—Unicompartmental Knee Arthroplasty
trial protocol.
3.2.38 VAS—Visual Analog Scale
4.4 The insurance coverage criteria for medical treatments
3.2.39 VR-6D—Veterans Rand (6 dimensions)
include: (1) that a net health outcome is achieved, (2) the
clinical trial results are applicable (generalizable) to the patient
3.2.40 VR-12—Veterans Rand (12 questions)
population, and (3) the clinical trial results are applicable
3.2.41 VR-36—Veterans Rand (36 questions)
(generalizable) to medical providers. Therefore, subgroup
3.2.42 WOMAC—Western Ontario and McMaster Universi-
analyses based on patient characteristics (age, sex) and pro-
ties Osteoarthritis Index
vider characteristics (academic medical center practice vs.
community orthopaedic practice setting, high vs. low surgical
3.2.43 WOMET—Western Ontario Meniscal Evaluation
Tool volume centers, urban vs. rural geographic practice locations)
F3108 − 19
should be included. Financial disclosures of clinical investiga- comparative effectiveness analyses used in coverage decisions.
tors should be provided based on Code of Federal Regulations Standardization of PRO measures is necessary to compare
Title 21 Part 54 “Financial Disclosure by Clinical Investiga- outcomes of procedures (10). Standardizing PRO measures for
tors.” implant and outcome registries will make comparative effec-
tiveness data available to the clinical and regulatory commu-
4.5 This guide does not suggest that all patient-reported
nities.
outcome instruments be used for each KRS. However, inclu-
6.1.2 PRO Measure Selection—PRO measure selection
sion of an outcome measure from each section will provide a
shall be pragmatic. High-respondent burden (too many ques-
thorough description of the benefits of KRS, including knee
tions) will result in poor rates of patient completion. High
function, pain relief, health-related quality of life including a
licensing fees make it difficult for not-for-profit registries to
health utility measure with the ability to calculate Quality
license the measure. Selection of PRO measures should be
Adjusted Life Years (QALYs) (6), and mobility/activity level.
based on whether they serve as primary or secondary outcomes
in clinical trials, as different PRO measures have strengths and
5. Significance and Use
weaknesses.
5.1 Approximately 650,000 primary total knee arthroplas-
6.1.3 Knee-Specific or Disease-Specific Outcome Instru-
ties (TKAs) and 50,000 revision TKAs are performed in the
ments (Table 1):
United States annually (7, 8). There are between 100,000 and
6.1.3.1 Knee Osteoarthritis/Arthroplasty—The knee-
200,000 anterior cruciate ligament knee injuries per year in the
specific PRO recommendation measure consensus for total
United States (9).
knee arthroplasty (TKA) or unicompartmental knee arthro-
plasty (UKA) from the American Academy of Orthopaedic
6. Use (Outcome Measures)
Surgeons (AAOS), theAmericanAssociation of Hip and Knee
6.1 Patient-Reported Outcomes (PROs):
Surgeons (AAHKS), and the American Joint Replacement
6.1.1 Patient-reported outcomes (PROs) are vital to under-
Registry(AJRR)istheKneeinjuryandOsteoarthritisOutcome
standing the value patients receive from health care. Value can
Score JR (KOOS JR) (11). The KOOS JR has been validated
be defined as the change in quality of life and function divided
for total knee replacement surgery (12).TheAJRR will present
by the total cost of care. Improvement in quality of life is most
national bench marking data for the KOOS JR. The most
commonly measured by QualityAdjusted Life Years (QALYs)
frequently used PROs for knee replacement surgery are the
(6). QALYs are required for cost-effectiveness analyses and
Oxford Knee Score (OKS) (13) and Knee injury and Osteoar-
thritis Outcome Score (KOOS) (14). The OKS is used in the
New Zealand Joint Registry (15) and the National Joint
https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRsearch.cfm?C-
Registry of England, Wales, and Northern Ireland (16).In
FRPart=54
TABLE 1 Recommended Patient Reported Outcome Measures for Knee Reconstructive Surgery
Health-Related Quality of Life Knee or Disease Specific Activity Level Pain
Knee Arthroplasty PROMIS Global Health KOOS JR LEAS NPRS
Veterans Rand 12 KOOS VAS, Likert
EQ-5D OKS
Veterans Rand-36 KSS
SF-12 WOMAC
SF-36 PROMIS Physical Function
ACL Reconstruction PROMIS Global Health KOOS Marx NPRS,
Veterans Rand 12 IKDC Tegner VAS, Likert
EQ-5D Lysholm
Meniscus Repair/ PROMIS Global Health KOOS Marx NPRS,
Reconstruction Veterans Rand 12 WOMET Tegner VAS, Likert
EQ-5D
Articular Cartilage PROMIS Global Health KOOS Marx NPRS,
Reconstruction
Veterans Rand 12 Tegner VAS, Likert
EQ-5D
Peri-Articular PROMIS Global Health KOOS LEAS NPRS,
Osteotomies Veterans Rand 12 KOOS JR Marx VAS, Likert
EQ-5D OKS
KSS
WOMAC
Peri-Articular PROMIS Global Health KOOS LEAS NPRS,
Fractures Veterans Rand 12 KOOS JR Marx VAS, Likert
EQ-5D OKS
KSS
WOMAC
F3108 − 19
additiontotheKOOSJR,theAJRRacceptsthefullKOOS (17, Score, andWOMAC. If the mean patient age is less than 40-50
18), Oxford Knee Score (OKS) (18, 19), Western Ontario and years, the knee arthritis PRO measures are likely to have
McMaster Universities Arthritis Index (WOMAC) (20), and
ceiling effects and the full KOOS should be used as recom-
Knee Society Score (KSS) (21) as Level 3 data on patient- mended for knee ligament and articular cartilage reconstruc-
reported outcomes. The Western Ontario McMaster Osteoar-
tion.
thritisIndex(WOMAC) (20)isalowerextremityosteoarthritis
6.1.4 General Health-Related Quality of Life (HRQL) Out-
disease-specific outcome instrument used for knee osteoarthri-
come Instruments (Table 1)—The AAOS, AAHKS, and Cen-
tis. A more recent validated PRO for osteoarthritis is the
ters for Medicare & Medicaid Services (CMS) have published
Patient-Reported Outcomes Measurement Information System
their consensus recommendations for health-related quality of
(PROMIS) Physical Function instrument (22).
life PROs for knee replacement surgery: PROMIS Global
6.1.3.2 Knee Anterior Cruciate Ligament (ACL)
Health 10 (22, 28) and Veterans Rand-12 (VR-12) (11). The
Reconstruction—The most common knee ligament reconstruc-
AJRR will present national bench marking data for PROMIS
tionsurgeryisforanteriorcruciateligamentruptures.Themost
Global Health and VR-12. Computer Adaptive Testing (CAT)
sensitivePROinstrumentforACLreconstructionsurgeryisthe
for PROMIS Global Health can reduce the respondent burden.
full KOOS instrument (14). The KOOS has been used by the
The European Quality of Life (EQ-5D) is used by the British
Multicenter Orthopaedic Outcomes Network (MOON) to pro-
National Health Service and National Joint Registry of
spectively evaluate ACL reconstruction surgery (23).
England, Wales, and Northern Ireland to assess the HRQL
Historically, the Lysholm Knee Questionnaire was used to
change after TKA (29). SF-36 and SF-12 (VR-36 and VR-12)
evaluate ACL reconstruction outcomes (24). The AAOS rec-
are frequently used as HRQLoutcomes instruments. However,
ommends the International Knee Documentation Committee
the quality-of-life summary measure (SF-6D) is a calculated
(IKDC) Subjective Knee Form for anterior cruciate ligament
summary score and does not allow patient preference weight-
reconstruction surgery (25).
ing for calculation of change in HRQL. Both the EQ-5D and
6.1.3.3 Knee Meniscus Reconstruction—The full KOOS SF-6D (VR-6D) can be used to calculate QALYs for cost-
(17) can be used to assess knee meniscus reconstructive
effectiveness or comparative-effectiveness analyses. However,
surgery. Clinically, meniscus reconstruction/repair may be Barton et al found that the EQ-5D was more appropriate for
combined with ligament reconstruction/repair, articular carti-
cost-effective analyses for knee pain relief (30). Goodwin et al
lage reconstruction, and peri-articular osteotomies so using the
found that the EQ-5D was more consistently responsive to
full KOOS allows the use of a single knee-specific PRO
change than the SF-6D after partial medial meniscectomy (31).
instrument for multiple procedures. The Western Ontario
6.1.5 Activity Level Scales (Table 1)—Activity scales can be
Meniscal Evaluation Tool (WOMET) was developed specifi-
used to subdivide patient populations into categories based on
cally for meniscal pathology and the outcome of meniscus
their level of activity to allow assessment of patients based on
surgery (26, 27).
greater or lesser activity level. The Lower Extremity Activity
6.1.3.4 Knee Articular Cartilage Reconstruction—The full
Scale (LEAS) (32) is a valid activity scale for knee osteoar-
KOOS (17) can be used to assess knee articular cartilage
thritis and revision knee replacement surgery. The LEAS
reconstructive surgery. Clinically, articular cartilage
received positive ratings for reliability and construct validity
reconstruction/repair may be combined with ligament
forhipandkneearthritis (33).TheLEAShasceilingeffectsfor
reconstruction/repair, meniscus reconstruction/repair, and peri-
elite athletes. The MarxActivity Rating Scale (34) and Tegner
articular osteotomies so using the full KOOS allows the use of
Activity Scale (35) are used in higher functioning athletic
a single knee-specific PRO instrument for multiple procedures.
populations. The Marx Activity Rating Scale allows more
6.1.3.5 Knee Peri-Articular Osteotomies—Knee peri- differentiation for elite function.
articular osteotomies are bone realignment procedures that
6.1.6 Pain Relief (Table 1)—Pain level can be measured
correct malalignment or change the force distribution between
with a Numeric Pain Rating Scale (NPRS), Visual Analog
the medial and lateral knee compartments. Because knee
Scale (VAS), or Likert scale.
peri-articular osteotomies are often combined with ligament
6.2 Safety:
reconstruction/repair, meniscus reconstruction/repair, and ar-
ticular cartilage reconstruction surgeries, using the full KOOS 6.2.1 Adverseeventratesareameasureofsafetyandshould
be defined by the study protocol. All adverse events shall be
allows the use of a single knee-specific PRO instrument for
multiple procedures. If the knee peri-articular osteotomies are recorded. Adverse events directly related to the KRS or
otherwise required by regulatory guidance shall be reported.
treatment for knee osteoarthritis, consider using the validated
PRO instruments for knee osteoarthritis/knee replacement Time windows for adverse event reporting should be based on
surgery (WOMAC, KOOS, KOOS JR, KSS, OKS) to allow
...