Clinical Data Presentations for Orthopedic Device Applications · Guidance for Industry and FDA Staff Clinical Data Presentations for Orthopedic Device Applications Document issued - [PDF Document] (2023)

Guidance for Industry and FDA Staff

Clinical Data Presentations for Orthopedic DeviceApplications

Document issued on: December 2, 2004

For questions regarding this document contact Barbara Buch, M.D.at 240-276-3737 or by email at [emailprotected]

U.S. Department of Health and Human Services Food and DrugAdministration

Center for Devices and Radiological Health

Orthopedic Devices Branch Division of General, Restorative, andNeurological Devices

Office of Device Evaluation

mailto:[emailprotected]

Contains Nonbinding Recommendations

Preface Public Comment Written comments and suggestions may besubmitted at any time for Agency consideration to the Division ofDockets Management, Food and Drug Administration, 5630 FishersLane, Room 1061, (HFA-305), Rockville, MD, 20852. When submittingcomments, please refer to the exact title of this guidancedocument. Comments may not be acted upon by the Agency until thedocument is next revised or updated.

Additional Copies Additional copies are available from theInternet at: http://www.fda.gov/cdrh/ode/guidance/1542.pdf, or toreceive this document by fax, call the CDRH Facts-On-Demand systemat 800-899-0381 or 301-827-0111 from a touch-tone telephone. Press1 to enter the system. At the second voice prompt, press 1 to ordera document. Enter the document number (1542) followed by the poundsign (#). Follow the remaining voice prompts to complete yourrequest.

http://www.fda.gov/cdrh/ode/guidance/1542.pdf

Contains Nonbinding Recommendations

Table of Contents 1.INTRODUCTION.............................................................................................................1

2. GENERAL DATA PRESENTATION: RECOMMENDED ELEMENTS................. 2

3. DESCRIPTION OF STUDY POPULATION................................................................5

4. PATIENT ACCOUNTING..............................................................................................6

5.SAFETY.............................................................................................................................7

6.EFFECTIVENESS..........................................................................................................11

7. PATIENT SUCCESSRESULTS...................................................................................12

8. ELEMENTS OF CLINICAL DATAPRESENTATIONS.......................................... 13

Contains Nonbinding Recommendations

Guidance for Industry and FDA Staff

Clinical Data Presentations for Orthopedic DeviceApplications

This guidance document represents the Food and DrugAdministration's (FDA's) current thinking on this topic. It doesnot create or confer any rights for or on any person and does notoperate to bind FDA or the public. You can use an alternativeapproach if the approach satisfies the requirements of theapplicable statutes and regulations. If you want to discuss analternative approach, contact the FDA staff responsible forimplementing this guidance document. If you cannot identify theappropriate FDA staff, call the appropriate number listed on thetitle page of this guidance document.

1. IntroductionThis guidance document is intended to provide youwith recommended general clinical data presentation formats forpremarket notifications (510(k)s), investigational device exemption(IDE) annual progress reports, premarket approval (PMA)applications, and annual and post-approval study reports fororthopedic implant devices. FDA is issuing this document to helpensure consistency and understanding between FDA and sponsors whendiscussing and presenting clinical data. We hope this guidance willconserve FDA and industry resources and facilitate timelyreview.

The data presentation formats described in this guidancedocument are intended to standardize presentations to facilitatereview of Orthopedic Devices Branch (ORDB) submissions. Thedescriptions and definitions used in this document are commonlyused in ORDB but may not be applicable to submissions in otherproduct areas.

This guidance document is not intended to provide you withinformation regarding the presentation of preclinical data, nor isit intended to describe all elements required for 510(k)s, IDEs, orPMAs. This guidance document supplements other FDA publications on510(k), IDE, and PMA submissions and should not be construed as areplacement for these documents.

Premarket Notification -510(k) Information For generalinformation on 510(k), refer to 21 CFR 807.87 and How to Prepare a510(k) Submission in CDRHs Device Advice athttp://www.fda.gov/cdrh/devadvice/314.html. In addition, there maybe other guidance documents specific to your type of device locatedon the FDA website, http://www.fda.gov/cdrh/guidance.html.

Investigational Device Exemption Information For general IDEinformation, refer to 21 CFR Part 812 or to the Guidance onInvestigational

page 1

http://www.fda.gov/cdrh/devadvice/314.htmlhttp://www.fda.gov/cdrh/guidance.html

Contains Nonbinding Recommendations

Device Exemptions Policies and Procedures, available athttp://www.fda.gov/cdrh/devadvice/ide/index.shtml..

Investigational Device Exemption Report Information There areadditional elements that are necessary for the completion of an IDEreport and they are outlined in FDA's document titled, "SuggestedFormat for IDE Progress Report," available athttp://www.fda.gov/cdrh/devadvice/ide/reports.shtml..

Premarket Approval Application (PMA) Information For general PMAinformation, refer to 21 CFR 814 orhttp://www.fda.gov/cdrh/devadvice/pma/app_methods.html. Inaddition, there may be other guidance documents specific to yourtype of device located on the FDA website,http://www.fda.gov/cdrh/guidance.html.

FDA's guidance documents, including this guidance, do notestablish legally enforceable responsibilities. Instead, guidancedocuments describe the Agency's current thinking on a topic andshould be viewed only as recommendations, unless specificregulatory or statutory requirements are cited. The use of the wordshould in Agency guidance documents means that something issuggested or recommended, but not required.

The Least Burdensome Approach The issues identified in thisguidance document represent those that we believe should beaddressed before your device can be marketed. In developing theguidance, we carefully considered the relevant statutory criteriafor Agency decision-making. We also considered the burden that maybe incurred in your attempt to follow the guidance and address theissues we have identified. We believe that we have considered theleast burdensome approach to resolving the issues presented in theguidance document. If, however, you believe that there is a lessburdensome way to address the issues, you should follow theprocedures outlined in the A Suggested Approach to Resolving LeastBurdensome Issues document. It is available on our Center web pageathttps://www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/UCM588914.pdf.

2. General Data Presentation: Recommended ElementsFor all datapresentations, we recommend that you clearly identify the number ofpatients evaluated at a given timepoint in any data presentation,in addition to the rate of improvement, for example, 64/75 patientsat 3 months rather than 85% at the 3 month timepoint. For anytable, a clear description of the population on which it is basedis important. In other words, if the result is 64/75, but thepopulation was 100 patients, you should account for the remaining25 patients.

We recommend that you consider the examples of formats for datapresentation in this document when you are designing your study tobetter assure that you collect adequate data. We recommend that youprovide the information below, as appropriate to support a 510(k),IDE annual report, or PMA (including PMA annual and post approvalstudy reports):

page 2

http://www.fda.gov/cdrh/devadvice/ide/index.shtmlhttp://www.fda.gov/cdrh/devadvice/ide/reports.shtmlhttp://www.fda.gov/cdrh/devadvice/pma/app_methods.htmlhttp://www.fda.gov/cdrh/guidance.htmlhttps://www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/UCM588914.pdf

Contains Nonbinding Recommendations

Description of the patient population This description includesa detailed discussion of the patient demographics in each treatmentgroup (see also section 3. Description of Study Population). Werecommend that you include any important demographic factors thatmay influence outcomes. This may include, but is not limitedto:

age gender co-morbid conditions work status smoking historydiagnostic groups.

Time course distribution of patient accounting This includes anaccounting of the status of each patient at each follow-up interval(e.g., theoretical follow-up, deaths, reoperations, revisions,removals, supplemental fixations, expected follow-up, actualfollow-up, and follow-up rate). These are discussed in section4.

Patient Accounting. We recommend that you include a cleardescription of the evaluation intervals pre- and post-treatment. Werecommend that an appropriate follow-up window for the evaluationinterval be pre-defined in the IDE protocol. We recommend thewindows around the intervals be distinct, as small as possible, andnot continuous, for example:

6 weeks 2 weeks 3 months 2 weeks 6 months 1 month 12 months 2months 24 months 2 months annually 2 months.

FDA believes that defining evaluation windows before initiatingthe study is optimal for comparing homogenous patients at eachdifferent follow-up timepoint in the postoperative period.

Written (narrative) descriptions of adverse events Written(narrative) descriptions of adverse events should include bothdetails of the events and demographic information (see Section 5.Safety). The details of the events should include:

any subsequent surgical interventions deaths protocol deviationssevere complications that occur, including any actions taken as aresult

page 3

Contains Nonbinding Recommendations

resolutions.

The demographic information should include: device implanteddiagnosis level or site of implantation pertinent medicalinformation.

We also recommend that you include any other information relatedto any association between the device and the event described.After identifying these events, if you change your study protocolor surgical technique, we recommend that you describe the changesand explain how these changes avoid or reduce the occurrence ofadverse events. Time course distributions of all adverse events forall patients receiving a treatment or implant We recommend that youpresent this distribution in a table (see Tables 3 and 4). Aseparate table should be presented to describe any subsequentsurgical interventions (see Table 5). Time course distributions ofeffectiveness parameters This distribution includes the followingparameters:

pain function radiographic assessment of fusion radiographicassessment of the implant health related quality of life return towork status other evaluation parameters appropriate to yourendpoints.

These time course distributions should provide the number ofpatients who meet each success criterion for each parameter (e.g.,as for pain, function) and should provide the number of patientsevaluated within a given group for each parameter (see Table 6).Time course distributions of the individual patient success ratesThis distribution should include success rates for all patientsover the course of the study (see section 7. Patient SuccessResults and Table 7). This allows for an appraisal of the patientsprogress over time. For each of the data presentations above, werecommend that you stratify patients into the following subgroups,as appropriate for the particular study design:

page 4

Contains Nonbinding Recommendations

investigational and control groups

group being studied (e.g., bilateral joints, unilateral joints,single level fusion, two level fusion, non inflammatory,inflammatory arthritis)

separate subgroups, where appropriate, unless the study ismasked

separate presentations for patients implanted outside of thestudy (e.g., compassionate use or continued access patients).

We also recommend that you provide separate presentations forpatients who do not follow the study protocol. These patients mayinclude those who did not meet all of the inclusion or exclusioncriteria, did not receive all of the study implant components, orpatients who are evaluated outside of the protocol-established timewindows. Therefore, we recommend that you provide clinical andstatistical rationales for their inclusion and for pooling of thesepatients data. General Safety Event Reporting We recommend that youreport all adverse events, regardless of rate of occurrence, asthey occur throughout the study. We may recommend additional ormore detailed data presentations for your application if describingspecific subsets of clinical data or other information will furtherelucidate the clinical performance of your device.

3. Description of Study Population We recommend that you providea complete description of the patient population. This verifiesthat the groups being evaluated are similar and that the variancesin the study groups are similar enough to compare the groupsstatistically and clinically. We recommend that you list thedemographics and all of the diagnoses and subgroups involved in theinvestigation, indicating the number of patients that have thatdiagnosis. This list should incorporate any important patientcharacteristics that may influence patient outcomes, such aspreoperative work status, education, and smoking status. Dependingon the inclusion and exclusion criteria, we recommend that you alsoinclude confounding factors such as the number of patients whoabuse alcohol, are involved in workers compensation or medicallitigation, race (if appropriate), medical co-morbidity, previoussurgery, degree of medication use, and involvement of otheradjacent or nonadjacent joints or spinal levels. We also recommendthat you include treatment demographics, such as operative times,blood loss, length of hospital stay, and post operative bracing,for each treatment group. Table 1 is a sample table for presentingdemographic information described above.

page 5

Contains Nonbinding Recommendations

Table 1 Demographic Information

I C Number of patients Men/women Mean age, year (range)

High School. Yes Smoking No Yes Alcohol use No Working PreopEmployment

Status Not working Diabetes Medical Conditions Cardiac, etcOsteoarthritis Osteonecrosis Rheumatoid arthritis

Diagnosis (# of patients and # of joints)

Other I= investigational group; C = control group 4. PatientAccounting Table 2 below is a sample table for patient accounting.Refer to section 8. Elements of Clinical Data Presentations forcomplete definitions of each of the elements included in thattable. Table 2 Patient Accounting Preop 6 wks 3 mo 6 mo 12 mo 24 mo36 mo I C I C I C I C I C I C I C Theoretical Deaths(cumulative)

Failures (cumulative)

Expected ActualA ActualB % Follow-up

I = investigational group; C = control group APatients withcomplete data for each endpoint, evaluated per protocol, in thewindow time frame. BPatients with any follow-up data reviewed orevaluated by investigator (all evaluated accounting).

page 6

Contains Nonbinding Recommendations

Where appropriate, an additional line for patients not yetoverdue (see 8. Elements of Clinical Data Presentations) may beadded to this table. As stated in section 8. Elements of ClinicalData Presentations, Actual includes those patients with completeassessment evaluations collected for each endpoint as per theprotocol. However, we understand that not all studies operate underideal conditions and, in some circumstances, not all patients arefollowed up at the intended time intervals or circumstances preventcollection of all data points to determine patient outcomes.Therefore, it may be appropriate to provide a patient accountingtable that also includes any patient who has been followed duringthe study regardless of whether data for all study end points hasbeen collected. This is referred to as all evaluated accounting.For an IDE or PMA report or an original PMA, FDA recommends aminimum of 85% follow-up of patients in each study cohort tomaintain the power of the study, avoid the potential for bias, andprovide sufficient data for analysis. If an IDE or PMA report doesnot show that the study is meeting this goal, we recommend that youprovide an adequate explanation for not meeting this goal anddescribe what steps are being taken to achieve adequate patientfollow-up. FDA may recommend that you perform a sensitivityanalysis at the time of final data submission to assist inexplaining, both clinically and statistically, the pooling of thosepatients with incomplete outcome data or out of window data withthose patients who have complete data collected per the protocol.Your analysis should clearly define the number of patientsevaluated within the time windows, before the time window, or afterthe time window for each evaluation interval. 5. Safety Werecommend that you organize the safety outcomes into two generalcategories: adverse events and subsequent secondary surgicalinterventions.

Adverse Events We recommend that you record and report allpreoperative, operative, and postoperative complications, whetherdevice-related or not. These include anticipated and unanticipatedcomplications. Pain, neurological, and function symptoms arecategorized as complications when a patients complaint for any ofthese symptoms results in an unscheduled visit or when a patientpresents with new or worsening symptoms as compared to the previousvisit. We recommend that you categorize or group adverse eventsaccording to the World Health Organization recommendations1 oranother accepted method of categorizing adverse events. Werecommend that you make a determination of device-related,operative site-related, and systemic (non-device related) events,if possible.

1World Health Organization (WHO), International ClassificationSystems, http://www.who.int/classifications. See also Chapter 5,Mental and Behavioural Disorders in The International StatisticalClassification of Diseases. WHO. See also the Primary Care Versionand Educational Kit in Related Health Problems, in InternationalClassification of Impairments, Disability and Handicaps. WHO.

page 7

http://www.who.int/classifications

Contains Nonbinding Recommendations

Table 3 below illustrates one way of presenting adverse eventsfor a total joint device, stratified by operative site and systemicevents. The time course of adverse events follows the same logic asthe patient accounting table. Each adverse event is identified bylisting it vertically down the left column of the table. Across thetop row of the table are the scheduled follow-up visits. The tableshould include the number of occurrences for each type of event andthe number of patients evaluated at each time interval.

Table 3 Adverse Events (Sample for Total Joint Device)Immed.

Post-op 3 mo 6 mo 12 mo 24 mo 36 mo

I C I C I C I C I C I C N= N= N= N= N= N= N= N= N= N= N= N=

Operative Site Events Infection Wound dehiscence DislocationFracture implant liner, head etc.

Fracture bone Other

Systemic Events Myocardial infarction Pulmonary emboli Urinarytract infection Other

N = number of patients evaluated at that time period. I =Investigational group; C = Control group Note: If patientsexperience more than one adverse event, we recommend that thenarratives describe recurrent events. Table 4 below is anothersimilar format for presenting a time course distribution of adverseevent for a spinal implant system.

page 8

Contains Nonbinding Recommendations

Table 4 Adverse Events (Sample for Spinal System) Op D/C-

6wks 6wks-3mo

3-6 mo 6-12 mo 12-22 mo 22-26 mo 26-34 mo

I C I C I C I C I C I C I C I C N= N= N= N= N= N= N= N= N= N= N=N= N= N= N= N=

Implant Related Implant displacement/loosening

Malpositioned implant

Non-union Subsidence Infection

Surgery Related Anatomic/ technical difficulty

Dural injury Retrograde ejaculation

Back/leg pain Graft site Neurological Spinal event Vascular,intraoperative

Vertebral fracture

Systemic Urinary tract infection

Cardiac events

Etc. I = Investigational group; C = Control group N = number ofpatients evaluated at that time period. Note: If patientsexperience more than one adverse event, we recommend that thenarratives describe recurrent events.

page 9

Contains Nonbinding Recommendations

Subsequent Secondary Surgical Interventions Some adverse eventslead to a subsequent secondary surgical intervention. We recommendthat you report subsequent secondary surgical interventions,separately from the presentation of other adverse events. Thereporting of these events is performed in the same manner asdeaths. For example, a patient was revised at or prior to theimmediate post-op examination. We suggest that you report thisrevision under the immediate post-op follow-up visit. If, at sometime between their immediate post-op examinations and theirindividually scheduled 3-month follow-ups, 2 additional patientshad revisions, then you should report these 2 revisions at the3-month follow-up timepoint because the examinations took placebetween the immediate post-op examination and the 3-monthfollow-up. FDA categorizes subsequent surgical interventions asfollows:

revisions removals reoperations supplemental fixations otherinterventions.

Refer to Section 8. Elements of Clinical Data Presentations forcomplete definitions of each of above categories of subsequentsurgical interventions. We recommend that you incorporate thedefinitions for subsequent secondary surgical interventions listedabove into an IDE protocol, to assure consistency in reportingoutcomes. We recommend that you capture the reason for eachsubsequent secondary surgical intervention and the action taken(e.g., replacement of a screw, placement of extra bone graftingmaterial, revision of a hip stem). Along with the presentation ofthe subsequent secondary surgical interventions pooled into thefive categories above, we recommend that each category be furtherstratified. For example, the revision category may be stratifiedinto separate categories such as revision for translated cage,removal of screws, depending on the reasons identified in aparticular study. As another example, the removal category may bestratified into removal for pain at the operative site after fusionor pseudoarthrosis, etc. FDA believes that some reasons forperforming a removal may constitute a failure; however, this isalso dependent on the device type. We recommend that you clearlyidentify which reasons for removal constitute a patient failure andprovide a rationale. For example, removal of a cage at any timeshould constitute a failure, however, removal of a pedicle screwsystem after fusion may not. If removal surgery is recommended inthe protocol for a given implant, we recommend that you clearlyindicate in your IDE protocol how such removals will be interpretedin terms of success and failure of the study. Additionally, werecommend that you identify any other subsequent surgicalintervention that constitutes a patient failure. Table 5 belowillustrates one way of presenting subsequent surgicalinterventions. You should indicate the number of patients whounderwent the specific intervention at each timepoint. If the

page 10

Contains Nonbinding Recommendations

number of implants differs from the number of patients, werecommend that you provide explanatory descriptions in the adverseevent narratives. Table 5 Subsequent Secondary SurgicalInterventions

Op D/C 6 wk 3 mo 6 mo 12 mo 24 mo Total events

# patients

Type

I C I C I C I C I C I C I C I C I C Revisions RemovalsSupplemental Fixations

Reoperations OtherA Total

I = investigational group; C = control group AThe other types ofsurgical interventions should be defined. Any events occurringafter 24 months may be placed in an additional column headed morethan 24 months. 6. Effectiveness The effectiveness clinical summarysubmitted in support of a PMA should be more detailed than that ofan annual report. When an evaluation method such as a Harris HipScore is used, we recommend that patient results be presented asthe number of implants with each rating score. We recommend thatyou summarize your results in tabular form and include eachstratified group being studied (e.g., bilateral joints, unilateraljoints, single level fusion, two level fusions, non inflammatoryarthritis, inflammatory arthritis). We recommend that you provide aseparate table for patients implanted outside of the study (e.g.,compassionate use or continued access patients). See the example inTable 6. Table 6 presents a typical orthopedic clinical evaluationsystem (Harris Hip Score). The number of patients and proceduresthat meet each rating is listed under the Total Score, Pain Score,and Function sections. Similar tables can be used for otherendpoint assessments.

page 11

Contains Nonbinding Recommendations

Table 6 General Effectiveness Data Summary Table Immed.

Post-op 3 mo 6 mo 12 mo 24 mo 24+ mo

I C I C I C I C I C I C N= N= N= N= N= N= N= N= N= N= N= N=

Total Score Rating Excellent (91-100) Good (81-90) Fair (71-80)Poor (

Contains Nonbinding Recommendations

Table 7 Effectiveness Data Summary Table for Spinal System Study6 wks 3 mo 6 mo 12 mo 24 mo 26+ mo I C I C I C I C I C I C N(Expected)A FusionB Oswestry score Neurologic status Disc heightBack pain Leg Pain SF-36 Physical SF-36 Mental Overall Success

I = investigational group; C = control group AThe number ofpatients expected at each timepoint in the top row. If the numberof patients evaluated differs from the N in any specific categorythe number of patients evaluated in that category should beprovided in the denominator for each parameter. BThe number ofpatients (not the percentage)/number of patients evaluated who meetthe success criteria for each endpoint at each timepoint areentered into the chart.

8. Elements of Clinical Data Presentations We included thefollowing descriptions of the elements used in this document toencourage consistency and enhance understanding between FDA andsponsors through a consistent vocabulary when discussing andpresenting clinical data. In some instances, the definitionsinclude FDAs recommendations that apply to the presentation formatsexemplified above. Theoretical Follow-up - The theoreticalfollow-up is the number of implants that would have been examinedif all patients returned on the exact anniversary of theirrespective initial surgery dates. The theoretical follow-up isdetermined by selecting a date of database closure. This is thedate the database was closed to the addition of information. Havingselected a date of database closure you can determine thetheoretical follow up. For each implant in the investigation, youshould determine the time difference between implantation and thedate of closure. Knowing this, you can determine which of thescheduled follow-up examinations the patient should have attended.This process is repeated for each implant enrolled in theinvestigation. The number of implants that should have beenexamined at each scheduled follow-up visit is summed, and thisnumber is the theoretical follow-up for each timepoint. To permitdata gathered from the patients up to the date of database closureto be entered into the report, the common practice is to select adate of closure in the recent past and report data collected up tothat point. We recommend that you include in the clinical report,any data recorded from an examination that took place on or beforedatabase closure, regardless of when you received it.

page 13

Contains Nonbinding Recommendations

Deaths This element is the number of deaths that have takenplace in the course of an investigation according to scheduledfollow-up visit. We recommend that you record the actual date ofthe patients death relative to the initial surgery in yournarrative explaining the nature of the circumstances, if known,related to the patients death. Failures - This element is thenumber of failures that have taken place in the course of theinvestigational study recorded according to the scheduled follow-upvisit. We recommend that you define as a failure any result thatwould remove the patient from the study, such as a secondaryintervention, severe adverse event, or other parameter that definesthe device as ineffective or unsafe. We also recommend that youdistinguish this failure from an effectiveness failure that wouldnot remove the patients from the study prior to the endpoint. Somepatient effectiveness results are determined failures only at the24-month period (or study endpoint), but these would not affect theaccounting table. We recommend that you record these in the finalresult table. You should record study failures in the varioustimepoints in the same manner as deaths. Not yet overdue - Patientsin this category are those within the evaluation time window whohave not been evaluated yet. For example, a patient who has not yetbeen evaluated and is 22 months post-operative is in the 24-monthfollow-up, but can be evaluated up to the 26-month timepoint and,thus, is not yet overdue. This category only applies in the case ofearly database closure for some statistical analyses plans. Incases where the not yet overdue category applies, we recommend thatyou add an additional row in the accounting table (Table 2). Actual- The number of patients actually evaluated during the follow-upwindow. For example, the 24-month timepoint includes the number ofpatients evaluated between 22 and 26 months postoperatively. Foreach evaluated patient, you should have data for each safety andeffectiveness endpoint of interest in the study, collected per theprotocol to be considered in this category. For example, if thereis a composite success-failure criterion, which includes pain,function, and radiographs, a patient should have documentation ofall of this data to be considered evaluated and a part of the groupwith actual follow-up. If a patient is evaluated at a time intervalbut the evaluation does not contain a complete set of data, or isconsidered to be a protocol violation, this patient is not includedin this category in this table. See table 2 above for a sample ofan all evaluated accounting table, which includes these patients inthe row titled evaluated. Expected - This element is the number ofpatients expected for a given time interval. These include thetheoretical number of patients who are due to be evaluated, lessthe number of patients who died or who were considered failures inthat time interval:

Theoretical [Deaths + Failures] = Expected

For certain statistical plans, we recommend that you alsosubtract the patients Not Yet Overdue from the Theoretical toobtain the Expected:

Theoretical [Deaths +Failures + Not yet overdue] = Expected Werecommend that Expected include patients lost to follow-up in allstudy designs.

page 14

Contains Nonbinding Recommendations

page 15

Follow-up rate - This element is the ratio of actual patientsevaluated to expected patients. The follow-up rate = Actual /Expected X 100, expressed as a percentage. Revision - A revision isa procedure that adjusts or in any way modifies or removes part ofthe original implant configuration, with or without replacement ofa component. A revision may also include adjusting the position ofthe original configuration. This may include removing a componentof a joint implant, such as a liner of a hip system, and onlyreplacing that single component. A revision may also include, inthe case of a spinal system, removal or repositioning of one of twocages that subsided or migrated without complete removal of bothdevices and graft. Removal - A removal is a procedure where all ofthe original system configuration is removed with or withoutreplacement due to, for example, mechanical failure of the device,pain, or infection. Reoperation - A reoperation is any surgicalprocedure that does not include removal, modification, or additionof any components to the system (e.g., drainage of a hematoma atthe surgical site). Supplemental fixation - A supplemental fixationis a procedure in which additional instrumentation not under studyin the protocol is implanted (e.g., supplemental placement of arod/screw system with a spinal fusion system, cerclage wiring witha hip implant). Other interventions - This category includes othersurgeries the patient incurs while enrolled in the study thatseemingly are unrelated to the implanted device. We recommend thatyou define the types and timing of these surgeries.

The Least Burdensome ApproachEducation levelDeaths(cumulative)Disc height