The US FDA’s proposed rule on laboratory-developed tests: Impacts on clinical laboratory testing

The Dalkon Shield was a contraceptive intrauterine device (IUD) developed by the Dalkon Corporation and marketed by the A.H. Robins Company. The Dalkon Shield was found to cause severe injury to a disproportionately large percentage of women, which eventually led to numerous lawsuits, in which juries awarded millions of dollars in compensatory and punitive damages.

The Dalkon shield was developed by Hugh J. Davis, a physician, and Irwin Lerner, an electrical engineer. Davis was a physician working as a gynecologist with an interest in limiting the effects of overpopulation in the world, as part of the Zero population growth theory popular in the 1960s.

He wrote: "While the upper socioeconomic tenth of the population can and does indulge in elaborate precoital rituals to control their fecundity the lowest socioeconomic tenth rejects such methods... The birth rate in the city of Baltimore in 1960 reflects this fact. There were 73 births per 1,000 white females in the highest economic class aged fifteen to forty-four, while in the lowest economic class there were 133 births. Thus, the segment of the population least able to discharge the responsibilities of parenthood was producing twice as many children per annum. The difference was nearly triple in the comparable non-white group."^[1]

He setup a family planning clinic for the Johns Hopkins Hospital in 1964, with the help of the Ortho Pharmaceutical Company, with many of his public patients being poor and black Baltimoreans. By the late 1960s, they were inserting up to 70 IUDs a month, some experimental, created by Johns Hopkins and Ortho.^[1]

In 1964, he began working with Irwin Lerner, an electrical engineer, on various medical devices, and over Christmas 1967, they decided to work on an IUD together. The design they came up with had a closed center (so as to not pose a risk of strangling the intestines if it migrated to the abdomen), and increase its surface area (and perhaps effectiveness) made of EVA (which had been approved by the FDA for use in food packaging), and fins were added to make it less likely to dislodge. This, in turn, made it more difficult to remove, and necessitated a stronger string, for which they used Supramid, a multifilament string encased in a nylon sheath.^[1] Previous IUD designs had used a monofilament plastic string to reduce the chance of wicking bacteria from the non-sterile vaginal canal to the sterile uterus. To manage this risk, they tied a knot at either end of the string and ran experiments to see if inky water would wick past the knot and up the string. It did not, and no further wick testing was done by the company.^[1]

Davis used the Johns Hopkins clinic to study the effects of his Dalkon shield on 640 women over a year-long period between 1968 and 1969. He reported a pregnancy rate of 1.1%, an expulsion rate of 2.3%, a retention rate of 94%, and reduced bleeding complications. However, this was later found to have numerous flaws; in the five months after the study was concluded, pregnancy rates were at 3-5%, it didn't have enough participants to give statistically significant results, and the average woman was enrolled for 5 months of the 12-month study; women who dropped out were not included in the results; some women were included after they had found success with the IUD, and Davis had recommended using spermicide during the most fertile days of patients cycles.^[1]

Lerner applied for a patent alone in 1968, and Lerner, Davis, and their attorney Robert Cohen formed the Dalkon Corporation.^[2][3][4]

After testing, the membrane of the shield was thinned and softened to help with extraction; copper sulfate was added to increase its radiopacity; metallic powdered copper was added to improve the plastic's strength; and they created a smaller version for women who had not given birth.^[1]

The addition of copper sulfate caused a problem for the company, since at the time the FDA was obliged to study and approve medical drugs and not devices, and although the IUD as a whole was a medical device, the copper was ruled to be a drug. To evade oversight, Robins claimed the copper sulfate was only there to help with imaging.^[1]

The effectiveness of these changes were not studied before the device went on the market.^[1]

In February 1970, Davis's study on his Dalkon Shield was published in the American Journal of Obstetrics and Gynecology. It did not mention his status as a co-inventor, or his financial interest in the device, nor was it peer-reviewed before publication. In the time between the study's submission to the journal and its publication, several women had become pregnant, making the pregnancy rate 3-5%, and taking it from better than other IUDs and oral contraceptives on the market to worst.^[1]

The Dalkon Corporation in 1970 gained another investor, J. Earl, M.D., a medical practitioner in Defiance, Ohio.^[5] Looking for a large retailer with marketing experience to sell their product, Earl met with a representative from A.H. Robins Company and sold them ownership rights and royalties. Robins was a pharmaceutical company but had no previous experience with birth control, nor had it made a medical device, an unregulated area at the time.^[6]

The Dalkon Shield was promoted as a safer alternative compared to birth control pills, which at the time were the subject of many safety concerns.^[5] Dr. Davis himself was a participant in the 1970 Nelson hearings, which were congressional hearings led by Senator Gaylord Nelson regarding the safety of oral contraceptives. He asserted that oral contraceptives with high doses of hormones were dangerous and that the efficacy of the pill was "greatly overrated".^[7]

In January 1971, Dalkon Shield went into the market, beginning in the United States and Puerto Rico, spearheaded by a large marketing campaign.^[3][6] At its peak, about 2.8 million women used the Dalkon Shield in the U.S.

While looking for a material for the tail string, Davis and Learner discovered Supramid. Supramid was a cable-like suture material made of hundreds of fine inner nylon fibers encased by a smooth nylon outer sheath that was commonly used to repair tears in the tendons of horses. In 1971, a quality control supervisor found that the strings were able to wick water and suggested heat-sealing the ends of the string to form a barrier against wicking, but management rejected the idea as cost prohibitive. In addition to the string's ability to wick bacteria, the string also had a propensity to deteriorate inside the body, adding additional risks and giving bacteria another avenue to enter the string. These properties allowed bacteria to pass through the cervix into the uterus, bypassing the cervical mucus, which normally acts as a barrier against infection.^{[6][8][9][10]}

Initial reports in the medical literature raised questions about whether its efficacy in preventing pregnancy and expulsion rate were as good as those claimed by the manufacturer, but failed to detect the tendency of the device to cause septic abortion and other severe infections.^[11]

Physicians reported that the Dalkon Shield was more difficult to insert and painful than other types of IUDs, with a doctor writing to A.H. Robins in 1971 that "I have found the procedure to be the most traumatic manipulation ever perpetrated on womanhood, and I have inserted thousands of other varieties."^[12]

The design of the insertion stick was also flawed, with the stick protruding past the end of the IUD. Physicians reported that it was easy to accidentally perforate the uterus with this tip.^[1]

In June 1973, the Centers for Disease Control and Prevention (CDC) conducted a survey of 34,544 physicians with practices in gynecology or obstetrics regarding women who had been hospitalized or had died with complications related to the use of an IUD in the previous 6 months. A total of 16,994 physicians responded, yielding 3,502 unique case reports of women hospitalized in the first 6 months of 1973. Based on the survey response rate, the CDC estimated that a total of 7,900 IUD-related hospitalizations occurred during this 6-month period. Based on an estimate of 3.2 million IUD users, the CDC estimated an annual device-related hospitalization rate of 5 per 1000 IUD users. The survey also provided five reports of device-related fatalities, with four of these related to severe infections. One of the five was associated with the Dalkon Shield. Based on these data, the CDC estimated an IUD-related fatality rate of 3 per million users per year of use, which it compared favorably to the mortality risks associated with pregnancy and other forms of contraception. Importantly, the survey showed that the Dalkon Shield was associated with an increased rate of pregnancy-associated complications leading to hospitalization.^[13]

By 1974, approximately 2.5 million women had received the Dalkon intrauterine device. In June of that year, the medical director of A.H. Robins published a letter to the editor of the British Medical Journal stating that the company was aware of an "apparent increase in the number of cases of septic abortions," including four fatalities, but stating that "there is no evidence of a direct cause-and-effect relationship between wearing of the Dalkon Shield and the occurrence of septicemia". The letter recommended precautions, including pregnancy tests for women who missed their period and the immediate removal of the device for women who were found to be pregnant.^[14] That same month, A.H. Robins suspended sales of the device in the United States at the urging of the Food and Drug Administration, but continued to sell it overseas.^[15] In October 1974, a series of four case reports of septic pregnancies were published in the journal Obstretics and Gynecology.^[16] In 1975, the CDC published a study associating the Dalkon Shield with a higher risk of spontaneous abortion-related death compared to other IUDs.^[17]

As many as 200,000 women made claims against the A.H. Robins company, mostly related to claims associated with pelvic inflammatory disease and loss of fertility. The company eventually filed for bankruptcy. The company's representatives argued that pelvic infections have a wide variety of causes, and that the Dalkon Shield was no more dangerous than other forms of birth control. Lawyers for the plaintiffs argued that the women they represented would be healthy and fertile today if not for the device. Scientists from the CDC stated that both arguments have merit.^[18]

In 1971, 5 months after the IUD was released, the string was found to wick bacteria into the uterus by a quality control supervisor, and the company chose to change nothing.^[6][19]

In June 1974, at the urging of the US FDA, Robins removed the IUD from the US market, but it continued to be marketed and sold internationally.^[15][20]

In September 1980, Robins wrote a letter to physicians recommending they remove the Dalkon shield from women still wearing them.^[19]

In 1984, 10 years after it was taken off the market in the US, the company put out newspaper, magazine, and television ads warning people of the risks and offering to pay for the shield's removal.^[12]

More than 327,000 lawsuits and claims were filed against the A.H. Robins Company – the largest tort liability case since asbestos. The federal judge, Miles W. Lord, attracted public commentary for his judgments, holding the corporate heads personally accountable, saying "Your company in the face of overwhelming evidence denies its guilt and continues its monstrous mischief. You have taken the bottom line as your guiding beacon and the low road as your route. This is corporate irresponsibility at its meanest." ^[21][22][23]

The cost of litigation and settlements (estimated at billions of dollars) led the company to file for Chapter 11 bankruptcy protection in August 1985.^[22]

The bankruptcy was legal but controversial at the time, as its assets were still sufficient to cover the current lawsuits and it was still making a profit, but by filing bankruptcy and creating a fixed-value trust fund for claimants, they were able to limit the damages paid.^[24] As part of the bankruptcy, they set up a 2.5 billion-dollar trust fund for claimants. The share price went up following the bankruptcy, and the owners were later able to sell the A.H. Robins for a profit to American Home Products (now Wyeth) in 1989, with American Home Products receiving tax deductions up to about 1 billion dollars from the trust fund for victims and related to purchasing a company that has been in bankruptcy.^[25]

More than half of the women in the class action suit were paid less than $1000, although some may have been paid out as much as $1 million in the cases of babies born with birth defects.^[26]

Overseas, the Dalkon shield continued to be marketed and sold for years after its withdrawal from the American market in 1974. In Australia, company memos informed their sales representatives of problems reported in the US, but this information was 'not to be used in doctor discussions'. It continued to be inserted as late as 1980.^[24]

By 1989, over 7,000 Australians were suing the company in relation to pregnancies, pelvic inflammatory disease, ectopic pregnancies, spontaneous septic abortions, and perforated uteri.^[20]

In 1976, the Medical Device Amendments to the Food, Drug, and Cosmetic Act mandated the U.S. Food and Drug Administration, for the first time, to require testing and approval of not just medications, but also medical devices, including IUDs.^[27]

Pharmaceutical companies were discouraged from investing in IUDs after the bankruptcy of Robins, deciding that they were less profitable and more controversial than oral contraceptives. There were no IUDs on the market in the USA between 1983 and 1988, and newer IUDs remained unpopular through the 1990s, likely due to memories of the Dalkon Shield amongst both physicians and the populace.^[12]

Only 1% of American women (aged 15-44) were using IUDs in 1995, but that number grew to 2.4% by 2004, and by 2017 the number had climbed to 14.0%, as a younger generation of women began embracing the newer IUDs as a safe, long-acting form of birth control.^[28]