Biodesign: The Process of Innovating Medical Technologies

Half-title......Page 3
Title......Page 5
Copyright......Page 6
Dedication......Page 7
Contents......Page 9
Foreword......Page 10
Preface......Page 11
The Biodesign Community......Page 16
Biographies......Page 21
Glossary......Page 23
IDENTIFY STAGE 1 Needs Finding......Page 39
Introduction......Page 42
Determine a mission......Page 43
Define acceptance criteria......Page 45
Articulating a strategic focus......Page 47
Global considerations in choosing a strategic focus......Page 50
Ethics in the biodesign innovation process......Page 51
Non-maleficence......Page 53
Justice or fairness......Page 54
Appendix 1.1.1......Page 56
Credits......Page 55
Notes......Page 57
Introduction......Page 58
Uncovering problems through observations......Page 59
Observational perspectives......Page 60
Preparing for observations......Page 62
Become part of the team......Page 63
Expect the unexpected......Page 64
Clues for identifying problems that may lead to clinical needs......Page 65
Documenting observations in an innovation notebook......Page 66
Knowing when to stop and transition to the next step......Page 67
Notes......Page 74
Introduction......Page 75
About the need statement......Page 76
Embedding a solution within the need......Page 77
Inappropriate definition of the scope......Page 78
Ongoing research and information gathering......Page 79
Incorporating outcome measures into the need statement......Page 80
Need criteria......Page 81
Needs and risk......Page 83
Blue-sky......Page 84
Mixed......Page 85
Notes......Page 88
1.1 Defining a strategic focus......Page 89
1.2 Problem identification and observation......Page 92
Notes......Page 93
IDENTIFY STAGE 2 Needs Screening......Page 95
Introduction......Page 98
Disease state fundamentals......Page 99
Approach to disease state analysis......Page 101
Anatomy and physiology......Page 102
Pathophysiology......Page 104
Clinical presentation......Page 105
Clinical outcomes......Page 106
Economic impact......Page 107
Summarizing the data......Page 108
Notes......Page 110
Introduction......Page 112
Other treatment considerations......Page 113
Finding gaps to identify treatment opportunities......Page 114
Approach to treatment analysis......Page 116
Overview of treatment options......Page 117
Clinical treatment profile......Page 119
Economic treatment profile......Page 122
Emerging treatment profile......Page 123
Treatment landscape......Page 125
Appendix 2.2.1......Page 129
Credits......Page 128
Notes......Page 131
Introduction......Page 133
Cycle of care analysis......Page 135
Flow of money analysis......Page 137
Patients......Page 139
Physicians......Page 140
Facilities......Page 142
Payers......Page 144
Understanding global stakeholders......Page 145
Linkages between stakeholder groups......Page 146
Ethical considerations in stakeholder analysis......Page 149
Notes......Page 153
Introduction......Page 155
Step 1: Market segmentation......Page 156
Segment patients based on symptoms and risk factors......Page 157
Segment patient/treatment/provider subgroups based on payers......Page 158
Step 2: Market size......Page 159
Porter’s five forces......Page 161
SWOT analysis......Page 163
InnerPulse revisited......Page 164
Step 4: Market needs......Page 165
Step 6: Target market......Page 166
Likelihood of segment to adopt new technology......Page 167
Bringing it all together......Page 169
Common pitfalls......Page 172
A note on global markets......Page 175
Notes......Page 179
Introduction......Page 181
Step 1: Select screening criteria......Page 182
Step 2: Assign ratings for each factor......Page 184
Step 3: Combine values to produce a score......Page 185
An alternative approach to filtering needs......Page 188
Need criteria......Page 194
References......Page 195
Credits......Page 197
Appendix 2.5.1......Page 198
Notes......Page 202
2.1 Disease state fundamentals......Page 203
2.2 Treatment options......Page 204
2.3 Stakeholder analysis......Page 206
2.4 Market analysis......Page 207
2.5 Needs filtering......Page 208
Notes......Page 209
INVENT STAGE 3 Concept Generation......Page 211
Introduction......Page 214
Ideation in the medtech field......Page 215
Brainstorming rules......Page 216
Special considerations for medtech brainstorming......Page 220
A final note on brainstorming......Page 227
Notes......Page 230
Introduction......Page 231
Transitioning from ideation to concept screening......Page 232
Clustering......Page 233
Concept mapping......Page 235
Comparing ideas against the need......Page 237
Notes......Page 242
3.1 Ideation and brainstorming......Page 243
3.2 Concept screening......Page 244
INVENT STAGE 4 Concept Selection......Page 245
Introduction......Page 248
Intellectual property fundamentals......Page 249
Criteria for obtaining a patent......Page 250
Freedom to operate: an introduction......Page 251
Before filing: the prior art search......Page 252
Search basics......Page 253
Provisional patents......Page 257
Part 1: Specification......Page 258
Part 3: Claims......Page 259
Filing and review of utility patents in the United States......Page 262
International patenting......Page 264
Intellectual property and patenting in India and China......Page 265
Inventorship and ownership......Page 266
Student, faculty, and employee inventors......Page 267
Non-disclosure agreements......Page 268
Credits......Page 275
Appendix 4.1.1......Page 276
Appendix 4.1.2......Page 295
Appendix 4.1.3......Page 307
Notes......Page 309
Introduction......Page 311
Food and Drug Administration background......Page 312
The FDA’s Center for Devices and Radiological Health......Page 313
Device classification......Page 314
The 510(k) process......Page 316
The PMA process......Page 319
Investigational device exemptions......Page 320
Humanitarian device exemptions......Page 321
Deciding on a regulatory pathway......Page 322
Europe......Page 325
Australia......Page 326
The BRIC countries......Page 327
OUS clinical trials and the FDA......Page 328
Credits......Page 330
Appendix 4.2.1......Page 331
Notes......Page 334
Introduction......Page 337
Reimbursement fundamentals......Page 338
Coding......Page 339
Payment......Page 340
More about physician reimbursement......Page 341
More about hospital inpatient coding and reimbursement......Page 342
New technology add-ons......Page 343
Reimbursement by private payers......Page 344
Preparing a reimbursement analysis......Page 345
A note on global reimbursement......Page 347
Germany......Page 349
India......Page 350
Credits......Page 353
Appendix 4.3.1......Page 354
Notes......Page 355
Introduction......Page 357
Choosing a business model......Page 358
Disposable products......Page 359
Reusable products......Page 362
Implantable products......Page 363
Capital equipment products......Page 365
Service......Page 367
Fee-per-use......Page 370
Over-the-counter products......Page 372
Validating a business model......Page 373
Operationalizing a business model......Page 374
Credits......Page 375
Appendix 4.4.1......Page 376
Notes......Page 377
Introduction......Page 378
Guidelines for effective prototyping......Page 379
2. Recognize the best category of prototype......Page 380
3. Isolate the functional blocks of a solution......Page 382
4. Understand what is known......Page 383
5. Define more detailed design requirements and technical specifications......Page 384
Timing of prototyping......Page 385
Bench testing and simulated use testing......Page 386
Tissue testing......Page 387
In-house versus outsourced prototype development......Page 388
General tips for effective prototyping......Page 392
Credits......Page 395
Layout drawing/cross-sectional drawing......Page 396
Computer-aided design......Page 397
Appendix 4.5.2......Page 399
Appendix 4.5.3......Page 401
Notes......Page 404
Introduction......Page 405
The Pugh method of concept selection......Page 406
Step 1: Identify user and design requirements......Page 407
Step 2: Weight user and design requirements......Page 408
Step 4: Assign scores and rank concepts using the selection matrix......Page 409
Notes......Page 415
4.1 Intellectual property basics......Page 416
4.3 Reimbursement basics......Page 417
4.4 Business models......Page 419
4.5 Prototyping......Page 420
4.6 Final concept selection......Page 421
IMPLEMENT STAGE 5 Development Strategy and Planning......Page 423
Introduction......Page 426
Strategies in pursuing patent coverage......Page 427
Freedom to operate strategies......Page 428
Hiring legal help......Page 431
International filing strategies......Page 432
Strategies in managing a patent portfolio......Page 433
Defensive strategies......Page 434
Offensive strategies......Page 435
Patent litigation......Page 437
Notes......Page 443
Introduction......Page 445
The linkage between R&D strategy and planning......Page 446
Defining high-level R&D milestones......Page 447
Identifying and prioritizing technical challenges......Page 448
R&D personnel......Page 452
Engineering resources......Page 454
Research and development testing methods......Page 455
Research and development timelines......Page 457
Credits......Page 461
Notes......Page 462
Introduction......Page 463
Clinical study goals......Page 464
Non-clinical, pre-clinical, and clinical phases of evaluation......Page 465
Non-clinical studies......Page 466
Institutional Animal Care and Use Committees......Page 467
First-in-man studies......Page 468
Case control studies......Page 469
Other trial nomenclature......Page 470
Location of clinical studies......Page 471
Endpoints......Page 472
Choosing investigators and centers......Page 473
Investigational device exemption......Page 474
Institutional Review Board approval......Page 475
Patient enrollment......Page 477
Informed consent and patient protection......Page 478
Research site staff......Page 479
Good clinical practices for conducting clinical trials......Page 480
A note on ethics: conflicts of interest in clinical trials......Page 481
Tips for designing and managing successful clinical trials......Page 482
Credits......Page 488
Appendix 5.3.1......Page 489
Appendix 5.3.2......Page 490
Sample size determination......Page 491
Appendix 5.3.3......Page 493
Notes......Page 494
Introduction......Page 496
Which center and division/branch to target?......Page 497
Strategy related to IDEs......Page 498
Strategies for 510(k) clearance......Page 499
Clinical data in 510(k) submissions......Page 501
Strategies for premarket approval (PMA)......Page 502
Premarket approval post-approval requirements......Page 503
Early CE marking of PMA devices......Page 506
Using EU clinical data for US and other regulatory approvals......Page 507
Notes......Page 510
Introduction......Page 511
Process management in product development and manufacturing......Page 512
Quality management systems......Page 514
Production and process controls......Page 516
Corrective and preventive actions......Page 518
Implementing a quality system......Page 519
Quality system regulations in the medical device industry: QSR and ISO......Page 521
Primary differences between QSR and ISO 13485......Page 522
Quality systems audits and what to expect......Page 523
Compliance actions/enforcement......Page 524
A note about recalls......Page 525
Applying the same rigor and discipline to managing other processes......Page 529
Credits......Page 533
More information about Medical Device Reporting......Page 534
Appendix 5.5.2......Page 535
Appendix 5.5.3......Page 537
Notes......Page 539
Introduction......Page 541
Reimbursement strategy fundamentals......Page 542
Developing a reimbursement strategy: balancing tactical and strategic considerations......Page 543
Revisiting reimbursement analysis......Page 544
Coding......Page 545
Coverage......Page 549
Payment......Page 551
The impact of reimbursement on clinical trials......Page 554
Advocacy......Page 555
Payer segmentation......Page 558
Publications......Page 559
Provider reimbursement support......Page 560
Global reimbursement issues......Page 562
Credits......Page 565
Cost-utility analysis......Page 566
Budget impact models......Page 567
Appendix 5.6.2......Page 568
Appendix 5.6.3......Page 569
Notes......Page 572
Introduction......Page 574
Marketing and stakeholder strategy fundamentals......Page 575
Value proposition and positioning......Page 576
Promotion and advocacy......Page 580
Pricing......Page 587
Medical marketing and ethics......Page 589
Notes......Page 592
Introduction......Page 594
Sales and distribution fundamentals......Page 595
The role of GPOs and IDNs in a national distributor model......Page 597
Specialized distributors......Page 598
Hybrid models......Page 599
Step 3: Pitching and closing......Page 602
Step 6: Account management......Page 603
The role of GPOs and IDNs in the direct model......Page 604
Sales force training......Page 605
Interaction with marketing......Page 606
Determining the most appropriate sales and distribution model......Page 608
Global sales......Page 613
Credits......Page 614
Appendix 5.8.1......Page 615
Notes......Page 617
Introduction......Page 618
The interplay between positional and capability-based advantages......Page 619
3. Strategic alliances......Page 620
Types of capability-based advantages in medtech......Page 621
5. General management......Page 622
First mover......Page 623
Me-too......Page 624
Original equipment manufacturer/licensing......Page 625
Using competitive advantage to define the basis for competition......Page 626
Developing a statement of competitive advantage......Page 629
Notes......Page 633
5.2 Research and development strategy......Page 634
5.3 Clinical strategy......Page 636
5.4 Regulatory strategy......Page 639
5.6 Reimbursement strategy......Page 640
5.7 Marketing and stakeholder strategy......Page 641
5.8 Sales and distribution strategy......Page 643
Training......Page 644
5.9 Competitive advantage and business strategy......Page 645
Note......Page 646
IMPLEMENT STAGE 6 Integration......Page 647
Notes......Page 649
Introduction......Page 650
Operating plan and financial model fundamentals......Page 651
Staffing plan......Page 652
Top-down model......Page 654
Bottom-up model......Page 656
Reconciliation with the top-down model......Page 661
Manufacturing costs......Page 662
Operating expenses......Page 664
Income statement......Page 666
Cash flow statement......Page 667
Cash balance and financing needs......Page 668
Proxy companies......Page 669
Complementarities with existing products and company strategy......Page 670
Credits......Page 674
High-level operating plan......Page 675
Financing milestones......Page 676
Clinical trials history......Page 678
Other milestones......Page 679
Operating costs and staffing levels......Page 680
Step 1: Structure the operating cost model......Page 681
Step 2: Assign staffing and costs to the model......Page 682
Additional cost and staffing considerations......Page 689
Clinical trial costs......Page 690
Lessons learned......Page 691
European strategy......Page 692
Reconciliation with the bottom-up market model......Page 693
Notes......Page 694
Introduction......Page 695
Business plan fundamentals......Page 696
The clinical need......Page 697
Management team......Page 698
Creating an effective executive summary......Page 699
Writing the business plan......Page 701
Business plans and funding......Page 704
Business plans and teams......Page 706
Business plans and intrapreneurship......Page 707
Credits......Page 709
The team......Page 710
Growing population with carotid plaques......Page 711
Management team......Page 712
Notes......Page 713
Introduction......Page 714
Venture capital (VC)......Page 715
Customers......Page 716
Choosing the best investor for the company......Page 717
Equity......Page 718
Debt......Page 719
Equity versus debt......Page 720
Approaching investors......Page 721
Understanding what investors want......Page 722
Investor due diligence......Page 723
Milestones......Page 724
Valuation......Page 725
Strategic considerations: how much funding between rounds and at what valuation?......Page 728
Term sheets......Page 730
Managing the funding process......Page 731
Initial public offering......Page 734
Credits......Page 737
Appendix 6.3.1......Page 738
Company valuation example......Page 740
Common sections of terms sheets......Page 742
Notes......Page 744
Introduction......Page 746
Returns, timing, and cost issues......Page 747
Partnering......Page 748
Sale/acquisition......Page 752
Building value toward a partnership, license, or sale......Page 753
Intellectual property......Page 754
Financial model......Page 755
Preparation for the process......Page 756
Managing an effective process......Page 757
A note on licensing when development occurs in an academic context......Page 761
Notes......Page 764
6.1 Operating plan and financial model......Page 765
6.3 Funding sources......Page 766
Into commercialization: what happened?......Page 767
Reflections on Acclarent’s past and future......Page 770
Credits......Page 771
Image credits......Page 772
Index......Page 773