Healthcare

TTK Healthcare is focused on bringing a high level of precision into their orthopedic manufacturing process. The Ortho Division is engaged in the manufacture of quality orthopaedic implants and instruments under the brand name “Altius”. TTK Healthcare Ltd acquired the orthopaedic business of M/s. Invicta Meditek Ltd. in July 2009 to consolidate their medical devices business.

The Challenges

In order to comply with the European Union Medical Device Directives – 90/385/EEC Active Implantable Medical Directives (AIMD), 93/42/EEC Medical Device Directive (MDD) and 98/79/EC In Vitro Diagnostic Device Directive (IVDD), its mandatory that manufacturers should conduct post-market surveillance (PMS). PMS is a collection of processes and activities that are used to monitor the performance of a medical device that accurately characterize the real-world device behaviour and clinical outcome. The flow of information into risk management comes from a wide variety of activities and one such is the clinical data obtained from post-marketing surveillance. PMS study methodology should adhere to relevant guidelines and standards and described in a Clinical Investigation Plan (CIP) that include a description of the rationale, objectives, endpoints, statistical methods, and clinical processes. A statistical analysis plan (SAP) offers a detailed description of the methods required and it should be performed in accordance with the SAP by experts experienced in medical device.

The Company has approached us to provide statistical Analysis Plan and the report for the Post market surveillance study. The objective is to track the feedback from end users (patients and surgeons) about our product to strive and make a continuous improvement in the safety, performance and efficacy aspects. The information filled out in pen/pencil is the feedback and typed out content in the sheet from the sales invoice information. The feedback was measured in qualitative scale (ex: good, very good, excellent, fair, poor) and the Knee score measures feedback quantitatively. Data discrepancy was challenging as the practice of scoring using knee score by the surgeons/patients is not a prevalent practice in this geography and is just an upcoming process, that was not mandatory. So, the surgeons who are acquainted with this methodology has provided this information and others are blanks. Missing data and outliers were one of the challenging when preparing SAP and reports.

Our Strategy

Guires Partnered with TTK for Statistical Analysis plan (SAP) and report preparation. Since the basis for SAP is the PMCF Strategy plan (PM surveillance programs) we have edited an existing PMCF to match with statistical analysis plan. That includes research questions, objectives, endpoint, study population (inclusion & Exclusion criteria), methods (with rationale of chosen study design, [not focused on selection of sites and investigators], duration of patient follow-up, data to be collected, (including questionnaire design for few of our clients), statistical analysis, a method of quality control of data a plan for conduct and an analysis of the data. Here, the objectives, efficacy end points and the hypotheses, study methods and rationale, study methods, will be set based on the outcome obtained from the draft data analysis.

Outcomes and Impact

The Basic data management activities were carried out such as coding and decoding, outliers, missing data etc. Data were categorized based on factors like (i)patient’s age, (ii)gender, (iii) type of diagnosis, (iv) type of deformity, (v) product sizes, (vi) complications (if any), all of which needs to be correlated to the feedback that is being provided by the hospitals/ surgeons and this was achieved via a valid hypothesis framing and testing. An in-depth analysis of data was conducted and presented in the form of a Statistical report. A clinical inference in the form of a Clinical Study Report (CSR) was prepared as to the findings based on the mutual understanding. All adverse events were carefully recorded and notified (see Regulation 16(10) of the Medical Devices Regulations 2002 (SI 2002 No 618) [1] and Annex X of the Medical Devices Directive 93/42 EEC). We have adhered to EN ISO 14155: 2011 for the design, conduct, recording and reporting of clinical investigations. We also adherence to statistical principles for clinical trials (International Conference for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use [ICH] E9)4 state that “the principal features of the eventual statistical analysis of the data should be described in the statistical section of the protocol.”

Lessons Learned

• Working with missing and outliners were one of the challenging areas. However, before looking at the data, our team of medical device researchers reviewed the study protocol with the biostatistician deputed exclusively for this project. With continuous scheduled meeting, the project execution plan was initiated after mutual discussion. Client was involved in all the activities and progress report was shared frequently.
•  An initial stage, statistical plan with TGF were prepared and sent it to client for their approval and any modifications or change request were carried within 24 hours.
• sample size calculation should make appropriate allowance for dropouts and any other anticipated protocol deviations. Not only should the sample size be increased to offset the loss of patients from the study or from their intended treatments, but it should also allow for the fact that the size of effect observed may be less than expected. Sample size calculation was one of the challenges that faced given the data shared by the client and we reviewed previous studies and protocols and came up with an appropriate sample size.

Experience on Post Market Surveillance Clinical Follow Up (PMCF)

We have conducted post-market surveillance (PMS) by adhering following guidelines that include followed European Union (EU) Medical Device Directives [Old; MDD93/42/EEC; new: MDR 2017/745/EU or as requested by the client].

For majority of our clients we have designed and developed PMCF Strategy plan (PM surveillance programs) such as designing a PMCF plan that includes research questions, objectives, endpoint, study population (inclusion & Exclusion criteria), methods (with rationale of chosen study design, [not focused on selection of sites and investigators], duration of patient follow-up, data to be collected, (including questionnaire design for few of our clients), statistical analysis, a method of quality control of data a plan for conduct and an analysis of the data. We have adhered to EN ISO 14155: 2011 for the design, conduct, recording and reporting of clinical investigations.

• The client had shared a CE-report which enabled to develop PMCF study plan.
• For few other clients, we have conducted data analyses from the registry (observational study) and also applied relevant retrospective data of treated patients. Statistical analyses were conducted based on the objectives/hypotheses set
• For one of our client, we helped them to develop a questionnaire and analytical methods specifically for their device which guaranteed fast and targeted data processing and evaluation.
• For other few clients based on the report, we have carried out revisions (reassessment) of clinical evaluation based on post-market surveillance data in accordance with MEDDEV 2.7.1/revision 4