Dr. Diana Zuckerman, testimony at FDA advisory meeting on breast implants

My name is Dr. Diana Zuckerman, and I am glad to speak today on behalf of the National Research Center for Women & Families.  Our nonprofit organization is dedicated to improving the health and safety of adults and children.

We have several concerns about the data that have been provided to you.

First, as you can see, many of the patients have been lost to follow-up.

Status of Post-Approval Studies

Study

Allergan

Follow Up

Mentor

Follow Up

Large  Study

2 years;

61% for silicone;

42% for saline

3 Years;

21% for silicone; 10%  for saline

Adjunct  Study

54% at 1-year

30% at 3-year

23% at 5-year

36% at 1-year

24% at 3-year

16% at 5-Year

Status of Post-approval Studies

Study

Allergan

Mentor

Enrollment

Follow Up

Enrollment

Follow Up

Core Study

715 Patients

65% at 10 years;  Primary Aug.  66%

Primary Rec.  75%

1008  Patients

58% at 8  years;  Primary  Aug. 54%

Primary  Recon. 67%

Our conclusion regarding the Post-Approval Studies: Many of these follow-up rates are too low to provide useful data for augmentation patients.

Our second point is about the reported rupture rates:  Since FDA reported the rupture rate in terms of the percentage of implants, it seems that this is a rate of rupture per implant, instead of  per patient. Previous data shows that the price per implant is approximately twice as high as per implant.

Mentor: Rupture Rate in MRI Cohort

Primary  Augmentation

Primary  Reconstruction

Revision

3 year

8 year

3 year

8 year

3 year

8 year

By Patient

.5%

.8%

4.8%

By Implant

.2%

13.6%

.5%

14%

3.9%

15.5%  augment.  21.3%  reconstr.

Allergan

Rupture Rate in MR I Cohort

Primary  Augmentation

Primary  Reconstruction

Revision

4 year

10 year

4 year

10 year

4 year

10 year

By Patient

3.4%

(N=166)

20.5%

(N=107)

10.9%

By Implant

1.7%

(N=331)

10.1%

13.1%

(N=182)

27.2%

5.7%

(N=150)

6.3%  augment.

6.7%  recontr.

Why the Poor Follow-up?

One company did a much better job than other. Why is that?  There is no excuse for Mentor’s poor performance because their patients and studies are very similar to Allergan’s.

Plastic surgeons tell women that implants are very safe. Does that contribute to patient’s lack of interest in participating in these studies? Or are the incentives poor?  Are they receiving free doctor’s exams or money for filling out lengthy questions?

In addition, we have heard from several patients that they were “fired” by their plastic surgeons when they reported implant problems.  That would obviously reduce the sample size and bias the results.

Cumulative Complications

Cumulative complication rates are decreasing in data the FDA has presented now, compared to a few years ago! That’s impossible. Cumulative complication rates should stay the same or increase from 4 years to 10 years. For example, for the Allergan data, swelling decreased from 23% to 9%.

Since come complication rates are going down, there is clearly a problem with the data. Either the company is not reporting complications correctly or the sample is changing in ways that reduce complications.

Allergan: Cumulative Complications

Health Complications

Primary Augmentation

3 years N=494

10 years N=455

Reoperation

21%

36%

Removal/replacement

8%

21%

Capsular Contracture III or IV

8%

19%

Breast pain

6%

11%

Loss of Nipple Sensation

3%

6%

Seroma

3%

2%

Hematoma

1%

2%

Skin sensation changes

2%

2%

Skin Rash

3%

1%

Redness

3%

1%

Infection

1%

1%

Bruising

9%

.4%

Allergan: Cumulative Complications

Cosmetic Complications

Primary Augmentation

3 years N=494

10 years N=455

Swelling

23%

9%

Implant malposition

3%

6%

Scarring

8%

4%

Asymmetry

3%

3%

Ptosis (sagging)

3%

2%

Implant palpability

2%

Wrinkling

2%

Mentor

Complications: Augmentation

By Patients, Cumulative KM Risk Rates of Complication with ≥ 1% Rate  through 2 and 3 years

Health Complications

Augmentation N=551

2-Year Rate

3-Year Rate

8-Year Rate

Reoperation

12%

15%

20%

Nipple sensation changes

9%

11%

12%

Capsular contracture III or IV

8%

8%

11%

Implant removal w/ or w/o  replacement

4%

5%

7%

Breast Mass

2%

2%

5%

Hematoma

3%

3%

3%

Breast sensation changes

2%

2%

3%

Breast Pain

2%

2%

3%

Infection

2%

2%

2%

Mentor

Complications: Augmentation

Cumulative KM Risk Rates of Complications through 2 and 3 yrs

Cosmetic Complications

Augmentation N=551

2-Year Rate

3-Year Rate

8-Year Rate

Hypertrophic scarring

6%

6%

Ptosis

2%

2%

Allergan

Cumulative Complications

Health complications

Primary reconstruction

3 years

N=221

10 years

N=98

Reoperation

46%

72%

Removal/replacement

25%

54%

CC III/IV

16%

25%

Breast Pain

6%

7%

Infection

2%

3%

Seroma

5%

2%

Redness

6%

2%

Skin Rash

3%

2%

Hematoma

2%

Bruising

4%

1%

Delayed wound healing

2%

1%

Allergan

Cumulative Complications

Cosmetic Complications

Primary Reconstruction

3-yrs N=221

10-years N=98

Asymmetry

15%

23%

Wrinkling

4%

10%

Swelling

16%

7%

Implant palpability

7%

Scarring

6%

6%

Implant malposition

5%

2%

Ptosis (sagging)

1%

0%

Mentor

Complications: Reconstruction

By patient, Cumulative KM Rates of Complications with ≥ 1% Rate through 2  and 3 years

Health Complication

Reconstruction

N=151

2-Year Rate

3-Year Rate

8-Year

Reoperation

25%

26%

39%

Implant removal w/ or w/o  replacement

12%

13%

23%

Capsular Contracture III/IV

7%

9%

15%

Infection

5%

5%

6%

Metastatic disease

2%

2%

6%

Breast Mass

3%

4%

5%

Seroma

5%

5%

5%

Breast pain

2%

2%

3%

Recurrent breast cancer

2%

2%

2%

Implant extrusion

1%

1%

1%

Hematoma extrusion

2%

2%

?

Necrosis

.4%

1%

?

Mentor seems to have stopped reporting certain complication rates. For example, asymmetry and ptosis, 2 complications for reconstruction patients, are simply not reported at 8 years.

What else might Mentor have decided not to report?  We don’t know.

Given these problems, it is difficult to have faith in the integrity of the Mentor data.

Mentor

Complications: Reconstruction

By patient, cumulative KM Risk Rates of Complications with with ≥ 1% Rate  through 2 and 3 years

Cosmetic Complication

Reconstruction

N=251

2-Year Rate

2-Year Rate

8-Year Rate

Implant malposition/displacement

2%

2%

3%

Asymmetry

5%

7%

?

Ptosis

3%

7%

?

Hypertrophic scarring

6%

6%

?

Wrinkling

2%

3%

?

Conclusions:

Incentives are lacking for companies or surgeons to do post-market research correctly. Enforcement for the FDA is needed to provide incentives.

Data are not capturing the problems many implant patients report.  This seems to be especially true for Mentor.

The FDA seems to depend on the research literature when data from the companies are lacking, but the research literature was funded by silicone and implant companies, and medical foundations with conflicts of interest.  We need unbiased data, and we should not excuse the companies from providing the data that was required as a condition of approval.