Serious adverse events responses

A large open-label flexible dose study (Sanchez-Lacay etal, 2001) utilizing nefa-zodone in the treatment of major depression in a predominantly monolingual, Hispanic Caribbean population (Dominican Republic, Puerto Rico, and Cuba) revealed similar response rates and an endpoint mean dosage when compared to previous nefazodone trials with non-Hispanic patients. No serious adverse events were reported, but 42% of the subjects did not complete the study for various reasons including side effects, family, or work responsibilities. 

An Investigator, not an employee of the Sponsor, is appointed to be responsible for the conduct of a trial. An appropriate quality system is followed and deviations from trial protocols are reported. Serious adverse events have to be reported to regulatory authorities within a specified time. 

All these studies indicate that the incidence of serious adverse events in such studies is very low and is comparable with the normal hazards of everyday life. Nevertheless, it must always be remembered that the volunteer is placing his or her welfare in the trust of the research physician, who therefore bears an enormous responsibility. 

Phase 1 dose-escalating and PK studies of Vatalanib were performed on a wide spectrum of tumors including colorectal, RCC, NSCLC, AML, ghoblas-toma, and prostate cancer. Dose ranged up to 2000 mg once daily or 1000 mg twice daily by oral administration. In most studies, results in patients with advanced solid tumors indicated that treatment was well tolerated with no drug-related serious adverse events. Tumor volume reduction was observed in some patients. The MTD was not reached with doses up to 1500 mg/day. The optimal dose was determined as 1250 mg/day. Measurable responses of tumor volume reduction were observed in 19% and 4% of the patients with RCC and ghoblastoma, respectively. Over 50% of patients achieved stable disease [282]. 

Given an inadequate drug response, or in patients with manic delirium who pose an immediate risk to themselves or others, we would consider ECT. Although BILAT stimulus electrode placement may be more effective than unilateral (UND) placement, this conclusion is currently only tentative, given the small number of patients studied. Finally, the combined use of ECT plus an antipsychotic may benefit the most treatment-resistant patient and has not been reported to induce serious adverse events (303, 304, 305 and 306). 

Serious adverse events occur in up to 6% of patients with anti-TNF therapy. The most important adverse effect of these drugs is infection due to suppression of the ThI inflammatory response. This may lead to serious infections such as bacterial sepsis, tuberculosis, invasive fungal organisms, reactivation of hepatitis B, listeriosis, and other opportunistic infections. Reactivation of latent tuberculosis, with dissemination, has occurred. Before administering anti-TNF therapy, all patients must undergo purified protein derivative (PPD) testing prophylactic therapy for tuberculosis is warranted for patients with positive test results. More common but usually less serious infections include upper respiratory infections (sinusitis, bronchitis, and pneumonia) and cellulitis. The risk of serious infections is increased markedly in patients taking concomitant corticosteroids. 

It is very important to assess the qualifications and availability of the subinvestigators conducting the study with the principal investigator, who is a field expert, as the subinvestigators will be responsible for performing the majority of study procedures and reporting serious adverse events. 

In 16 patients with treatment-resistant schizophrenia (defined as non-responsiveness to at least three antipsychotic drugs from at least two different chemical classes), olanzapine was effective treatment in a significant proportion no serious adverse events were associated with maintenance doses of 10-40 mg/day, and no subjects dropped out (26). 

The Hexavalent Study Group has compared the immuno-genicity and safety of a new liquid hexavalent vaccine against diphtheria, tetanus, pertussis, poliomyelitis, hepatitis B, and Haemophilus influenzae type b (DTP + IPV + HB + Hib vaccine, manufactured by Aventis Pasteur MSD, Lyon, France) with two reference vaccines, the pentavalent DTP -I- IPV -i- Hib vaccine and the monovalent hepatitis B vaccine, administrated separately at the same visit (9). Infants were randomized to receive either the hexavalent vaccine (n = 423) or (administered at different local sites) the pentavalent and the HB vaccine (n = 425) at 2, 4, and 6 months of age. The hexavalent vaccine was well tolerated (for details, see the monograph Pertussis vaccines). At least one local reaction was reported in 20% of injections with hexavalent vaccine compared with 16% after the receipt of pentavalent vaccine or 3.8% after the receipt of hepatitis B vaccine. These reactions were generally mild and transient. At least one systemic reaction was reported in 46% of injections with hexavalent vaccine, whereas the respective rate for the recipients of pentavalent and HB vaccine was 42%. No vaccine-related serious adverse event occurred during the study. The hexavalent vaccine provided immune responses adequate for protection against the six diseases. 

On p. 48 of the article, there is a footnote that states AZT brings DNA synthesis to a halt. AZT was shelved as a chemotherapy agent on account of this extreme toxicity.) It may be added that Farber s article produced an outpouring of counterattacks in the letters to the editor. Farber s follow-up book Serious Adverse Events An Uncensored History of AIDS, published in 2006, met with a similar response. 

---